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Probiotics

Gut microbiome interventions — probiotic strains, fermented foods, and prebiotic fiber for mood, immunity, and digestion.

Evidence is mixed

Gut-brain axis effects are real but highly strain-specific — evidence for Lactobacillus helveticus R0052 + Bifidobacterium longum R0175 on anxiety is the strongest human RCT signal. Most commercial probiotic blends have not been tested at specific doses in RCTs. Effects on digestion are more robust than effects on mood or cognition.

Evidence base

Min quality:

50 papers

RCTTop journalWikiHigh evidence score

Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial

Elmira Akbari, Zatollah Asemi, Reza Daneshvar Kakhaki +5 more · Frontiers in Aging Neuroscience · 2016 · 908 citations

A 12-week course of daily probiotic milk containing four bacterial strains improved cognitive function (measured by MMSE score) by approximately 28% in Alzheimer's patients, while also reducing inflammation and oxidative stress markers, suggesting the gut-brain axis may be a viable target for cognitive support.

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RCTWikiHigh evidence score

Clinical, gut microbial and neural effects of a probiotic add-on therapy in depressed patients: a randomized controlled trial

Anna-Chiara Schaub, Else Schneider, Jorge F. Vázquez‐Castellanos +11 more · Translational Psychiatry · 2022 · 225 citations

A 31-day course of a high-dose multi-strain probiotic (900 billion CFU/day) added to standard treatment reduced depressive symptoms more than placebo in hospitalized depressed patients, with the effect persisting four weeks after stopping, and was linked to increased Lactobacillus in the gut and reduced putamen brain activation to neutral faces.

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RCTHigh evidence score

World Gastroenterology Organisation Global Guidelines: Probiotics and Prebiotics

Francisco Guarner, Mary Ellen Sanders, Hania Szajewska +9 more · Journal of Clinical Gastroenterology · 2024 · 173 citations

The concept of beneficial microbes was first suggested by Elie Metchnikoff who postulated that lactic acid bacteria offered health benefits capable of promoting longevity. Disorders of the intestinal tract were frequently treated with viable nonpathogenic bacteria to change or replace the intestinal microbiota. The German professor Alfred Nissle isolated a nonpathogenic strain of Escherichia coli from the feces of a First World War soldier who did not develop enterocolitis during a severe outbreak of shigellosis. In Japan, Dr. Minoru Shirota isolated Lacticaseibacillus paracasei strain Shirota to battle diarrheal outbreaks. Today, a search of human clinical trials in PubMed shows that over 1500 trials have been published on probiotics. Although these studies are heterogeneous with regard to the strains and populations included, accumulated evidence supports the view that benefits are measurable across many different outcomes that have been assessed. This article is an update of a previous publication in the Journal of Clinical Gastroenterology,1 and is based on the guideline recently posted on the WGO website. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.2 Our glossary of terms is based on the definitions proposed by the International Scientific Association of Probiotics and Prebiotics. Lactobacilli, along with species of Bifidobacterium, have historically been common probiotics. In 2020, the genus Lactobacillus underwent a major restructuring to better address the wide diversity of microbes assigned to the genus. Twenty-three new genera were defined, including some with well-studied probiotic species (Table 1). TABLE 1 - New Names for Some Prominent Former Lactobacillus Probiotic Species. Still Included in the Lactobacillus Genus are Lactobacillus acidophilus, L. gasseri, L. crispatus, L. johnsonii, L. helveticus, and L. delbrueckii subsp. bulgaricus (Sometimes Abbreviated as L. bulgaricus). Former name New name Lactobacillus casei Lacticaseibacillus casei Lactobacillus paracasei Lacticaseibacillus paracasei Lactobacillus rhamnosus Lacticaseibacillus rhamnosus Lactobacillus plantarum Lactiplantibacillus plantarum Lactobacillus brevis Levilactobacillus brevis Lactobacillus salivarius Ligilactobacillus salivarius Lactobacillus fermentum Limosilactobacillus fermentum Lactobacillus reuteri Limosilactobacillus reuteri From the International Scientific Association for Probiotics and Prebiotics (ISAPP), “The big breakup of Lactobacillus,” available at https://www.nestlenutrition-institute.org/infographics/big-breakup-lactobacillus. GLOSSARY OF TERMS - Probiotics Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host Prebiotic A selectively fermented ingredient that results in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health Synbiotics A mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host. There are 2 types of synbiotic: complementary (mixtures of probiotics and prebiotics) and synergistic (mixtures of live microbes selected to utilize a coadministered substrate for a health effect) Postbiotic A preparation of inanimate microorganisms and/or their components that confers a health benefit on the host The yeast Saccharomyces boulardii and some E. coli and Bacillus species are also used. Newcomers to the probiotic ranks include Clostridium butyricum, recently approved as a novel food in the European Union. Lactic Acid Bacteria, which have been used for the preservation of food by fermentation for thousands of years, may also potentially impart health benefits. However, the term “probiotic” should be reserved for live microbes that have been shown in controlled human studies to impart a health benefit. Fermentation is globally applied in the preservation of a range of raw agricultural materials, such as cereals, roots, tubers, fruit and vegetables, milk, meat, and fish. The prebiotic concept, first proposed by Gibson and Roberfroid in 1995,3 is a more recent one than probiotics. The key aspects of a prebiotic are that it is nondigestible by the host and that it leads to health benefits for the consumer through a positive influence on the resident beneficial microbes. The administration or use of prebiotics or probiotics is intended to influence the gut environment, which is inhabited by trillions of microbes, for the benefit of human health. Both probiotics and prebiotics have been shown to have beneficial effects that extend beyond the gut, but this guideline will focus on gut effects. Prebiotics typically consist of nonstarch polysaccharides and oligosaccharides, although other substances are being studied as candidate prebiotics—such as resistant starch, conjugated linoleic acid, and polyphenols. Most prebiotics are used as food ingredients in foods such as biscuits, cereals, chocolate, spreads, and dairy products. Commonly known prebiotics are: Oligofructose (fructooligosaccharide, FOS) Inulin Galactooligosaccharides (GOSs) Lactulose Breast milk oligosaccharides (human milk oligosaccharides or HMOs) Lactulose is a synthetic disaccharide used as a drug for the treatment of constipation and hepatic encephalopathy. The prebiotic oligofructose is found naturally in many foods, such as wheat, onions, bananas, honey, garlic, and leeks. Oligofructose can also be isolated from chicory root or synthesized enzymatically from sucrose. Fermentation of oligofructose in the colon may result in several physiologic effects, including: Increasing the numbers of bifidobacteria in the colon Increasing calcium absorption Increasing fecal weight Shortening gastrointestinal transit time Lowering blood lipid levels However, the extent to which these physiological effects may be experienced by a consumer varies due to a number of factors, including baseline gut microbiota and diet. It has been hypothesized that the increase in colonic bifidobacteria benefits human health by producing compounds that inhibit potential pathogens, by reducing blood ammonia levels, and by producing vitamins and digestive enzymes. Synbiotics were originally described as appropriate combinations of prebiotics and probiotics. More recently, the concept of synbiotics has evolved to include both complementary and synergistic synbiotics. A complementary synbiotic is defined simply as a mixture of probiotic(s) and prebiotic(s), where the 2 components meet the criteria defined for each, including proper characterization, and are used at a dose shown to provide a health benefit. However, a synergistic synbiotic has been described as a mixture of a live microbe selected to utilize a coadministered substrate, which together leads to a documented health benefit. The components of a synergistic synbiotic do not need to independently meet the criteria for a probiotic or prebiotic (Fig. 1).FIGURE 1: Composition of complementary and synergistic synbiotics. A complementary synbiotic combines a prebiotic and a probiotic, which work independently to elicit one or more health benefits. The prebiotic functions by modulating the resident microbiota to elicit a health benefit. The synergistic synbiotic is composed of a substrate that is utilized by the coadministered live microorganism, enhancing its functionality. Components of synergistic synbiotics work together (not independently) to bring about the resulting health benefits. (Reproduced from Swanson et al4 CC BY 4.0).Genera, Species, and Strains Used as Probiotics A probiotic strain is identified by the genus, species, subspecies (if applicable), and an alphanumeric designation that identifies a specific strain (Table 2). In the scientific community, there is an agreed nomenclature for genus, species, and subspecies names. Strain designations, product names, and trade names are not controlled by the scientific community. According to the guidelines of the World Health Organization (WHO) and Food and Agriculture Organization (FAO; http://www.fao.org/3/a-a0512e.pdf), probiotic manufacturers should deposit their strains in an internationally recognized culture collection. Such will an designation to shows a of strains and the names with TABLE 2 - Used for Probiotic Genus Strain designation International strain designation Strain name Lacticaseibacillus rhamnosus The product name shown in the may be used in some of Food and TABLE - of Probiotic and Prebiotic The and the can be by or in the Probiotics or Prebiotics Probiotics benefits to increase to and increase A both and to food benefits food and for with to an for to inhibit intestinal for with Prebiotics of absorption of host Strain for probiotics are the to probiotic evidence is to benefits as the specific gastrointestinal in this to specific strains or strain combinations of probiotics at the of in a clinical should specific strains to the benefits based on human Some strains will have that may for and However, an concept in the of probiotics is to that some of probiotic activity are different species, or probiotics may in a with regard to their to intestinal or microbiota. the to acid or in the colon may be a benefit by many different probiotic some probiotic benefits may be by different strains of well-studied species of probiotic It is common in the of probiotics for and to include Such an is of the different strains are to be for the benefit being assessed. such should focus on The functions of both probiotics and prebiotics for gastrointestinal are with the microbes that in the human Prebiotics are utilized by beneficial of the community, promoting health. probiotics and host or probiotics and resident microbes a key for the health. The a number of microbes, in the colon and comprising of that over are in the colon of an human being a of than and are also with a in terms of may bacteria microbes an of to human the of species and the diversity is or of by the host by at through and by In the fecal composition is over In the human gut the 2 and and for more than of microbes. 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Prebiotics may also Probiotic strains may health effects through one or more of several identified Probiotics may the intestinal by by with or potential microbes, by such as and by with host through (Fig. can to of potential pathogens, an intestinal environment, the intestinal of and of the to are to the beneficial effects, including of the and of which is one of the recognized of of microbiota and probiotic with the host. The microbiota and probiotics with the host in and and of and (Reproduced with from through the have been in many of the A range of product food through available (Table TABLE - of Probiotics of Food or health with for the consumer or health health or with or health or drug to or drug to or or and the bacteria in is specific to The that can be on these types of on in the Most probiotics and prebiotics are as foods or products. of or is to be and are at the health a specific in where the and the of the product for use in is From a scientific of a probiotic product as on the should species with nomenclature with recognized names Strain designation of strain at the of The which should be based on of the physiological of the physiological as by for and The for probiotics was at in to a It is that the probiotic will at an of to by through the of foods, and on the is a Most from is based on strains than product names, which can on the It can be to probiotic strains to specific and not are to this has been in and the by from and to available evidence and The of probiotic on the are not to may not to The that are to probiotic include of of typically by through the of that of and nomenclature used to the genus, species, and and a strain designation for strain in the The dose for probiotics varies on the strain and Although many in the range of some have been shown to be at levels, some subsp. was in the of at the dose of other probiotic is to It is not to a dose that is for the should be based on human studies a health benefit. probiotics are are to during product typically in that at the of the it not the on the manufacturers will the dose at the (not at the time of probiotic strains have the of to during However, evidence of the of that for probiotics. 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Lactobacillus rhamnosus 2 and treatment Lactobacillus reuteri and L. reuteri 1 of 2 and treatment Saccharomyces boulardii or 2 in effects and Bacillus 2 2 in effects and of with strains of Lactobacillus L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. on for Lactobacillus 2 on for Lactobacillus and on for Lactobacillus subsp. on for of with and Lactobacillus in with Bacillus was more than in reducing strains of Lactobacillus L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. of of in Lactulose 1 of hepatic and from hepatic strains of L. L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. of hepatic strains of Lactobacillus L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. hepatic with Lactobacillus L. acidophilus, bifidobacteria and L. casei hepatic Lactobacillus hepatic Lactobacillus plantarum a of hepatic Lactobacillus bulgaricus and with L. and in Lactobacillus L. L. acidophilus, and L. 2 in along with and of in and activity Lactobacillus paracasei L. plantarum L. and L. delbrueckii subsp. bulgaricus and in and activity with subsp. and in in and 1 2 in and also Lactobacillus plantarum 1 2 in of and Escherichia coli on of Lactobacillus rhamnosus L. plantarum L. and in in and Lactobacillus subsp. L. L. delbrueckii subsp. bulgaricus on of Saccharomyces boulardii 2 in 1 2 in of in fermented milk and Lactobacillus in in Lactobacillus 2 on of Lactobacillus rhamnosus L. rhamnosus 2 in of on of Galactooligosaccharides 2 on of Lactobacillus plantarum L. plantarum or in strains of Lactobacillus L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. of 1 of and of in Bacillus 2 in and in Lactobacillus and L. reuteri on of in Lactobacillus rhamnosus L. plantarum and subsp. on of in Saccharomyces of in and Bacillus Lactobacillus L. delbrueckii bulgaricus L. casei L. plantarum L. rhamnosus L. L. salivarius and 2 of in with Lactobacillus 1 of 1 of Lactobacillus and L. subsp. of and Lactobacillus casei L. plantarum subsp. of in on the of in on the constipation Lactobacillus L. rhamnosus and of and in Lactobacillus reuteri 1 2 of and Lactulose 1 Prebiotics are used as Oligofructose 1 of by and Lactobacillus paracasei L. rhamnosus L. and in and strains Lactobacillus acidophilus, and 1 of colonic transit and in with constipation subsp. subsp. 1 or 1 in in with than Lactulose Bacillus 2 to the time to constipation as to Lactobacillus L. casei L. and with and colonic transit time in with constipation Lactobacillus casei strain Shirota in fermented milk of or in the Lactobacillus casei subsp. 2 in in Lactobacillus paracasei in in Lactobacillus salivarius L. The probiotic in with the and more than treatment Lactobacillus reuteri 1 and with and in of Lactobacillus plantarum L. and dose of of Lactobacillus L. rhamnosus L. paracasei and of due to Lactobacillus casei strain Shirota in fermented milk the of Lactobacillus in fermented milk of the of the of strains of Lactobacillus L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. bacteria 2 of strains of Lactobacillus L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. bacteria 2 of clinical in strains of Lactobacillus L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. bacteria 2 of in Clostridium of in strains of Lactobacillus L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. bacteria of Escherichia coli Nissle viable bacteria 2 2 of viable Lactobacillus acidophilus, and 2 in the clinical to with with live of Lactobacillus delbrueckii subsp. bulgaricus and of strain of product 1 Lactobacillus 1 and Lactobacillus rhamnosus 1 Lactobacillus plantarum L. plantarum of of with with of TABLE - of Probiotics and/or Prebiotics in Probiotic strain dose Probiotics as a 1 the of the of on an including in L. rhamnosus for 1 of of and for 1 of L. reuteri 1 to for 1 of L. rhamnosus L. reuteri 2 for for 1 of for of L. paracasei and for of L. rhamnosus strains or for of but not of of L. delbrueckii L. acidophilus, for of L. rhamnosus and L. a for the of of and of Probiotics as a 1 of for the of treatment 1 of and L. rhamnosus for the of treatment 1 of and probiotic Lactobacillus Lactobacillus Lacticaseibacillus paracasei plantarum Lacticaseibacillus rhamnosus and Ligilactobacillus salivarius for the of treatment and for of but not The of L. rhamnosus and 2 for the of treatment of of 1 and of of L. rhamnosus for the of the 1 of of enterocolitis and of 1 Some specific strains of probiotic may be for L. rhamnosus From 1 to 1 and and to 1 and subsp. or L. reuteri or 1 1 this strain is by but not or subsp. L. with milk subsp. L. rhamnosus and Probiotics as a 1 and/or effects of treatment 1 it was the of and in reducing gastrointestinal effects with Lactobacillus plantarum subsp. and boulardii L. plantarum L. and boulardii for and effects milk L. casei for Probiotics as a 1 L. reuteri for at 1 and/or time in but its in is for 2 and/or time in with L. rhamnosus and L. reuteri in a dose of of of for and/or time in L. paracasei L. plantarum L. L. delbrueckii subsp. bulgaricus and and for in L. reuteri to for 1 time in both and 1 evidence for the use of probiotics a in with L. reuteri to 2 1 L. rhamnosus to 1 Probiotics as a 1 clinical in with A mixture of strains paracasei L. plantarum L. L. delbrueckii subsp. bulgaricus and as or in to 1 2 and of Escherichia coli Nissle or in to and is available for and of A mixture of strains paracasei L. plantarum L. L. delbrueckii subsp. bulgaricus and 1 2 in with and Lactobacillus in with other strains of or Lactobacillus may be beneficial for levels of and lipid and in with However, evidence not of the beneficial strain of probiotic 1 studies with the strain boulardii European and European for and not controlled and probiotics to be described by genus, species, and strain in studies the benefit. the strain was not the strain designation was not positive studies studies results for its were studies were not studies in which the results for the were not a of the probiotic strains or prebiotics found to have a beneficial is clinical evidence to a specific probiotic strain and/or prebiotic is should be the of the of the The of in the trials was not assessed. The may not be as the publication of new studies is other probiotics and/or prebiotics in controlled trials may be The of evidence may the different shown are used in the The of the is There is evidence from studies to the in terms of The do not provide of but levels of evidence to

RCTHigh evidence score

Probiotics synergized with conventional regimen in managing Parkinson’s disease

Hairong Sun, Feiyan Zhao, Yuanyuan Liu +13 more · npj Parkinson s Disease · 2022 · 129 citations

Parkinson's disease (PD) is mainly managed by pharmacological therapy (e.g., Benserazide and dopamine agonists). However, prolonged use of these drugs would gradually diminish their dopaminergic effect. Gut dysbiosis was observed in some patients with PD, suggesting close association between the gut microbiome and PD. Probiotics modulate the host's gut microbiota beneficially. A 3-month randomized, double-blind, placebo-controlled clinical trial was conducted to investigate the beneficial effect of probiotic co-administration in patients with PD. Eighty-two PD patients were recruited and randomly divided into probiotic [n = 48; Bifidobacterium animalis subsp. lactis Probio-M8 (Probio-M8), Benserazide, dopamine agonists] and placebo (n = 34; placebo, Benserazide, dopamine agonists) groups. Finally, 45 and 29 patients from Probio-M8 and placebo groups provided complete fecal and serum samples for further omics analysis, respectively. The results showed that Probio-M8 co-administration conferred added benefits by improving sleep quality, alleviating anxiety, and gastrointestinal symptoms. Metagenomic analysis showed that, after the intervention, there were significantly more species-level genome bins (SGBs) of Bifidobacterium animalis, Ruminococcaceae, and Lachnospira, while less Lactobacillus fermentum and Klebsiella oxytoca in Probio-M8 group (P < 0.05). Interestingly, Lactobacillus fermentum correlated positively with the scores of UPDRS-III, HAMA, HAMD-17, and negatively with MMSE. Klebsiella oxytoca correlated negatively with feces hardness. Moreover, co-administering Probio-M8 increased SGBs involved in tryptophan degradation, gamma-aminobutyric acid, short-chain fatty acids, and secondary bile acid biosynthesis, as well as serum acetic acid and dopamine levels (P < 0.05). Taken together, Probio-M8 synergized with the conventional regimen and strengthened the clinical efficacy in managing PD, accompanied by modifications of the host's gut microbiome, gut microbial metabolic potential, and serum metabolites.

ObservationalModerate

Feed your microbes to deal with stress: a psychobiotic diet impacts microbial stability and perceived stress in a healthy adult population

Kirsten Berding, Thomaz F. S. Bastiaanssen, Gerard M. Moloney +9 more · Molecular Psychiatry · 2022 · 141 citations

The impact of diet on the microbiota composition and the role of diet in supporting optimal mental health have received much attention in the last decade. However, whether whole dietary approaches can exert psychobiotic effects is largely understudied. Thus, we investigated the influence of a psychobiotic diet (high in prebiotic and fermented foods) on the microbial profile and function as well as on mental health outcomes in a healthy human population. Forty-five adults were randomized into either a psychobiotic (n = 24) or control (n = 21) diet for 4 weeks. Fecal microbiota composition and function was characterized using shotgun sequencing. Stress, overall health and diet were assessed using validated questionnaires. Metabolic profiling of plasma, urine and fecal samples was performed. Intervention with a psychobiotic diet resulted in reductions of perceived stress (32% in diet vs. 17% in control group), but not between groups. Similarly, biological marker of stress were not affected. Additionally, higher adherence to the diet resulted in stronger decreases in perceived stress. While the dietary intervention elicited only subtle changes in microbial composition and function, significant changes in the level of 40 specific fecal lipids and urinary tryptophan metabolites were observed. Lastly, microbial volatility was linked to greater changes in perceived stress scores in those on the psychobiotic diet. These results highlight that dietary approaches can be used to reduce perceived stress in a human cohort. Using microbiota-targeted diets to positively modulate gut-brain communication holds possibilities for the reduction of stress and stress-associated disorders, but additional research is warranted to investigate underlying mechanisms, including the role of the microbiota.

Systematic ReviewHigh evidence score

Probiotic Bacteria in Dietetic Products for Infants: A Commentary by the ESPGHAN Committee on Nutrition

Carlo Agostoni, Irené Axelsson, Christian Braegger +8 more · Journal of Pediatric Gastroenterology and Nutrition · 2004 · 158 citations

INTRODUCTION There is considerable interest in including probiotics in dietetic products for children, and such products are marketed in many countries. This commentary by the ESPGHAN Committee on Nutrition reviews available information on the effects of adding probiotic bacteria to infant formulas, follow-on formulas, and special medical foods. It also discusses the safety of these products and the appropriate conditions for their use. The Committee reviewed expert consensus documents on probiotics in foods and dietetic products for infants. The Committee also systematically reviewed all randomized clinical trials on dietetic products containing probiotics which involved infants. Because probiotics are available in many forms, such as capsules and powders, the Committee reviewed controlled clinical trials that examined the effects of different probiotic preparations for infants. The conclusions of this commentary may require revision in the future as new information becomes available. GUT MICROFLORA Most studies report that the stool flora of breast-fed infants differs from that of formula-fed infants (1). Breast-fed infant stools contain predominantly Bifidobacterium and Lactobacillus, which may account for as much as 90% of the total flora (2). In contrast, the flora of formula-fed infants is more diverse, containing Bacteroides, Bifidobacterium, Staphylococcus, Escherichia coli, and Clostridia (2–4). The species of Bifidobacterium in the stools of breast- and formula-fed infants differ (5). A variety of factors has been proposed as causes for the different fecal flora of breast- and formula-fed infants, including the lower content and different composition of proteins in human milk, its lower phosphorus content, the large variety of oligosaccharides in human milk, and numerous humoral and cellular mediators of immunologic function in breast milk (6). The gut flora appear to modulate health and well-being of the host (7,8). The lower incidence of gastrointestinal and other infections in breast-fed infants (9–11) may in part be related to their gut flora. Bifidobacterium and Lactobacillus inhibit the growth of pathogenic microorganisms through the production of lactic, acetic, and other organic acids, with a consequent decrease of intraluminal pH, whereas formula feeding favors propionate and butyrate production and a near neutral fecal pH. Moreover, Bifidobacterium and Lactobacillus compete with potentially pathogenic bacteria for nutrients and epithelial adhesion sites. The gut flora also promote the recovery of energy and nutrients through fermentation of nondigestible carbohydrate, nitrogen salvage, and beneficial effects on mucosal growth and water and nutrient absorption (12). Evidence is accumulating that gut flora also modulate mucosal physiology, barrier function, and systemic immunologic and inflammatory responses (13). The growing interest in the role of the bacterial gut flora on health has stimulated different strategies to modify the human intestinal flora, including the provision of bacteria considered probiotics and nondigestible carbohydrates considered prebiotics. DEFINITIONS The term probiotic was introduced in 1965 by Still-well and Lilly (14). A widely accepted definition of probiotics is “live microbial food ingredients that are beneficial to health” (15). However, the scientific basis of this definition has recently been questioned because animal studies suggest that some probiotic effects can be achieved by nonviable bacteria and even by bacterial DNA (16–18). Therefore, probiotics have more recently been defined as “microbial cell preparations or components of microbial cells with a beneficial effect on the health and well being of the host” (19). Prebiotics are “non-digestible food components that benefit the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thereby improve host health” (15). Synbiotics are “mixtures of probiotics and prebiotics that benefit the host by improving the survival and implantation of live microbial dietary supplements in the gastrointestinal tract” (15). EXPERT COMMITTEE REPORTS ON THE USE OF PROBIOTICS IN HUMANS The joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria concluded that probiotic strains belong primarily to two genera, Lactobacillus and Bifidobacterium, which must survive the passage through the digestive tract and proliferate in the large bowel. Enterococcus strains should not be used as probiotic microorganisms (20). It was recommended that strains be named according to the International Code of Nomenclature, be deposited in an internationally recognized culture collection, and that strain identification be performed by phenotypic tests followed by genetic identification with methods such as DNA/DNA hybridization and 16sRNA sequencing (21). Stock cultures should be maintained under appropriate conditions and be checked periodically for strain identity and probiotic properties. Because no in vitro tests predict the probiotic activity of a strain, activity should be determined in clinical trials following accepted standards of scientific quality. Beneficial effects must be related to dosage regimens and duration of use in each product or strain. Safety considerations should include transmission of antibiotic or drug resistance inherent in some probiotic microorganisms. The Expert Consultation further recommended that dried milk powders containing live lactic acid bacteria should preserve adequate numbers of viable probiotic bacteria with stable probiotic properties throughout shelf-life, and that labeling should include the microbial species or strain and the proportion of viable organisms. Claims for health benefits should be substantiated with scientific evidence. Subsequently published Guidelines for the Evaluation of Probiotics (22) further emphasize the need to fully evaluate the safety of probiotics, in particular the risk of infection in subjects with compromised immunity and subjects at risk for endocarditis. The French Agency for Food Safety (AFFSA) reviewed the safety of probiotics in infants, excluding genetically modified and nonviable microorganisms from its definition of probiotics (23). The report distinguished two distinct periods of modification of intestinal colonization: the first week of life, when breast-fed infants develop a flora dominated by bifidobacteria and formula-fed infants develop a more complex flora, and the period when complementary feeding is started. The report concluded that the possible health consequences of the enzymatic activities of the more diversified flora of formula-fed infants compared with that of breast-fed infants are not known. For infants without lactose intolerance, the lactose-fermenting capacity of probiotic bacteria confers no appreciable benefit. No conclusion was made as to whether reduced bacterial translocation, seen in animals supplemented with certain probiotic strains, occurred in infants. The Agency recommended for safety reasons that probiotics should not be given to immunocompromised or premature infants. In addition to requirements on strain identity, viability, strain stability, and number of probiotic bacteria in a food at the end of its shelf life, the Agency recommended that instructions for preparation, storage, and heating of the formula be specific to guarantee the survival of the desired number of microorganisms until the time of feeding. The Agency further recommended that nutritional, physiological, and therapeutic effects be documented in appropriate clinical studies. The Scientific Committee on Food of the European Commission also commented on the use of probiotic bacteria in food products for infants (24). It recommended that infant formulas with probiotic microorganisms should be marketed only if their benefit and safety have been evaluated according to the principles outlined by the same Committee. The Committee did not object to the addition of probiotic bacteria to follow-on formulas. However, the Committee stated that only bacterial strains with identity and genetic stability demonstrated by cultural and molecular methods should be used. The identity of the probiotic strain should be described by molecular methods in a dossier and be available to the food control authorities. The content of viable bacteria should be adequate throughout shelf-life to achieve 106 to 108 colony-forming units (CFU) per gram of formula prepared as ready for consumption. SYSTEMATIC REVIEW OF CLINICAL TRIALS ON DIETETIC PRODUCTS WITH PROBIOTICS IN INFANTS Three databases (MEDLINE, EMBASE, and Cochrane Controlled Trials Register) were searched up to July 2003. We reviewed randomized and quasirandomized (i.e., allocating participants according to date of birth, the number of hospital records, etc.) controlled trials (RCT) of infant or follow-up formulas, or special medical foods, supplemented with bacteria generally considered probiotics. All references to review articles in the identified trials were reviewed. A separate search was made using the names of authors considered experts in this field. No limit was imposed as to the language of publication. Letters to the editor, abstracts, and proceedings from scientific meetings were excluded. Only clinically important outcomes (end points) were considered. Surrogate outcome measures (laboratory parameters) were excluded. After the exclusion criteria were applied, the search strategies yielded six articles on the clinical effects of feeding dietetic products supplemented with probiotics, including four on infant or follow-on formulas (25–28) and two on special medical foods (29,30) (Table 1). When scoring trial quality using Jadad’s criteria (31), only one study was of good methodological quality (25).TABLE 1: Trials with dietetic products for infants and young children supplemented with probioticsTABLE 1: ContinuedA. Clinical Effects Infant and follow-on formulas. One high-quality double-blind RCT of 55 infants and young children aged 5 to 24 months in a chronic medical care hospital in a developed country found that administration of standard infant formula supplemented with Bifidobacterium lactis (formerly called Bifidobacterium bifidum) (1.9 × 108 CFU/g powdered formula) and Streptococcus thermophilus (0.14 × 108 CFU/g) reduced the prevalence of nosocomial diarrhea compared with placebo (7% versus 31%; relative risk [RR]: 0.2; 95% confidence interval [CI]: 0.06–0.8). The risk of rotavirus gastroenteritis was significantly lower in those receiving probiotics supplemented formula (RR: 0.3; 95% CI: 0.09–0.8). Feeding B. bifidum and S. thermophilus led to a significantly lower rate of rotavirus shedding (25). One low quality RCT (no blinding, allocation concealment unclear, dropout and withdrawal rate not documented) involving 175 children living in an orphanage in a developing country reported no protective effect of infant formula supplemented with Bifidobacterium Bb12 (108 CFU/g) alone on episodes of diarrhea (40/62; 65%) or in combination with S. thermophilus (dose not given) (29/56; 52%) compared with placebo (14/57; 25%). Rotavirus accounted for only 3 of 81 (3.7%) episodes of diarrhea, and bacterial pathogens accounted for 45 of 81 (56%) episodes of diarrhea (26). Foods for special medical purposes. Two small RCTs of infants with atopic dermatitis and cow’s milk allergy during formula feeding or breastfeeding were found (29,30). Neither study provided details of randomization and blinding. Allocation concealment was unclear. In the first study (29), infants (n = 27) with atopic eczema and cow’s milk allergy were randomly assigned to receive extensively hydrolyzed whey formula supplemented with Lactobacillus GG (5 × 108 CFU/g formula) or placebo for 1 month. There was a statistically significant reduction in the clinical score of atopic dermatitis (SCORAD) during the 1-month study. However, by 2 months the SCORAD was similar in both groups. In the second study (30), infants (n = 27) with atopic eczema during exclusive breastfeeding were randomly assigned to receive extensively hydrolyzed whey formula supplemented with Lactobacillus GG (3 × 108 CFU/g), or Bifidobacterium lactis Bb-12 (1 × 109 CFU/g), or the same formula without probiotics. No details on the duration of intervention were given. After 2 months, a statistically significant reduction in SCORAD score was observed in the groups consuming probiotics compared to placebo. A significant change in the SCORAD scores at the 2-month evaluation was seen in 9 of 9 patients receiving B. lactis Bb-12, and in 9 of 9 patients in the Lactobacillus GG group, as compared with 4 of 9 patients not receiving probiotics. In conclusion, there are very limited published data on the clinical effects of probiotic supplementation of infant formulas, follow-up formulas, and special medical foods. Although some benefits are until more studies are available is not possible to that the clinical effects of probiotic supplementation are or therapeutic for B. It is recommended that the safety of breast milk be evaluated are introduced to the important part of this evaluation is the on have growth data from studies the effect of infant formulas and foods for special medical purposes. Infant and follow-on formulas. Three RCTs growth of children formulas supplemented with probiotic bacteria were found (Table The first RCT evaluated infants randomized to formula with or without Streptococcus thermophilus and Lactobacillus for the first 2 months of There were infants in each group, and the two groups were compared with a of fully breast-fed infants. and were at birth, 1 and 2 No data on growth were given. It was stated that that the of feeding growth during the first 2 months of without significant there was no information on this conclusion was In the second RCT infants aged 5 to 24 months with chronic and in a chronic medical care hospital were randomized to receive standard infant formula (n = or the same formula supplemented with Bifidobacterium bifidum and Streptococcus thermophilus (n = The duration of was 81 There was no in the and of the groups at was no data were on growth during the and the groups were not It was stated only that all infants maintained or their during the study. The RCT of children aged months was in a in The children were randomized to formulas, which for one infant formula with Bifidobacterium lactis Bb-12 and Streptococcus thermophilus (n = one the same formula with only Bb-12 (n = and one formula without probiotics (n = and were and the change in standard score was used to evaluate There were no significant in rate of the groups. The two groups with probiotics a significantly growth the end of the intervention did the control The was to the is of quality because no details of randomization were allocation concealment was unclear, there were significant the study groups in of no data were given on of formula and the follow-up at months was (Table 1). Foods for special medical purposes. Only one study has growth in infants randomly assigned extensively hydrolyzed whey formula with Bifidobacterium lactis Bb-12, Lactobacillus or no probiotics and were at and 2 and months of It was stated that the growth of all children was the groups were not In conclusion, only one study has provided growth data adequate to the effects of infant formula with probiotics. This study was performed in infants living in a in One of that study was its large from to months, because growth and of growth are different in young infants and This study found a effect of probiotics on because the is of the conclusion is of limited The other studies were small with to effects on of the studies did not the growth a of no conclusions can be made the of probiotic bacteria in dietetic products on infant However, there are no from the available data that probiotics have effects on CLINICAL TRIALS ON THE USE OF PROBIOTICS IN There is on the effects of probiotics in other powdered documented are the therapeutic effects of certain probiotic strains in as recently in two reviews A beneficial effect was found in the of diarrhea by which was strain and benefit also to be achieved in diarrhea by other no was found in bacterial Beneficial effects were more when with probiotics was in the of Two reviews that probiotics given in combination with the risk of diarrhea In the and strains of have been used in this However, with the trials were performed in and the conclusion may not be to the Committee at the studies in trials were One small RCT children with and found no significant of diarrhea 95% CI: A further double-blind RCT at and Bifidobacterium methodological (i.e., small of definition of diarrhea as an end conclusions Two RCTs a effect of GG for diarrhea in children in are dosage of Lactobacillus GG used in in and in the of diarrhea may be for There are no randomized studies in children on the incidence of diarrhea by Three studies of the of probiotics for nosocomial diarrhea were One small trial beneficial effects of Bifidobacterium bifidum and Streptococcus thermophilus (25). Evidence for the of Lactobacillus GG is with one RCT benefit and different A diarrhea was in a trial of Lactobacillus GG used in a developing country in a with a of This benefit was in children to months of were not breast = However, no effect was found in a similar trial in In a study of children 1 to of from care milk containing Lactobacillus GG no significant diarrhea, as by the number of with or the proportion of children without diarrhea during the study However, the with Lactobacillus GG to have with a reduction in the number of by gastrointestinal and during the study = The same study demonstrated a reduction of infections (RR: 95% CI: number to 95% CI: and antibiotic (RR: 95% CI: 95% CI: in children milk with Lactobacillus After for of these was statistically In the same significant reduction in the risk of was seen = controlled for and = the use of Lactobacillus GG is more has not been study from found that Lactobacillus GG (1 × given to the for 2 to 4 and to the for months reduced the incidence of atopic eczema in children at 2 (RR: and 4 of (RR: One study that a combination of and given for to children 1 to of be beneficial in the of atopic dermatitis of possible and of the clinical effects by further in other is from animal and patients with inflammatory have the of the in the of the in clinical probiotics have only limited In children with a trial of Lactobacillus GG that Lactobacillus GG reduced intestinal and activity However, a randomized study children with small and large in that Lactobacillus GG in a of 109 was not in when to standard for In children, that the health effect of probiotics is the reduction of the duration of The benefit of probiotics in other conditions is to be However, there is a of to suggest that may be in the of nosocomial and diarrhea, and Effects appear to be strain specific and be from strain to strain. REPORTS ON THE USE OF PROBIOTICS IN INFANTS and low are risk factors for and from and It has been that administration of probiotics to premature with of intestinal different from those of infection and and the use of studies have examined the of probiotics to the gut of and infants. on the of Lactobacillus GG have rate was reported in a randomized controlled trial of One RCT in very infants found that infants were supplemented with Bifidobacterium of fecal at 2 of and feeding Clinical outcomes were not reported In the administration of and Bifidobacterium to all in an care with a incidence of reduced the incidence of compared with The study is limited by not being A randomized controlled trial in infants found that Lactobacillus GG supplementation × 109 with the first feeding did not tract or In only a limited number of controlled trials have health outcomes following administration of probiotic in infants. studies are The safety of probiotics has been extensively reviewed recently Although the probiotics used in clinical trials generally have been described as and well there have been some that this conclusion In microorganisms in probiotics have been from patients with or infections and infections with Lactobacillus species in infants and children have been reported all patients with infections in these studies have conditions to in the of or in the of In of the to have from the Only a limited number of have been reported in which the was not to be related to the use or of a probiotic product In these patients conditions were of infection with Bifidobacterium during supplementation with this have not been A report from that the use of Lactobacillus GG in food has not in an incidence of Lactobacillus or in the proportion of Lactobacillus all of with probiotics has not been reported in infants or children is a of the published have concluded that the risk of infection with probiotic or bifidobacteria is similar to that of infection with strains, and that of such products is a risk to including immunocompromised effects in which probiotics a role include and However, the available data from and clinical not that such effects with the probiotic in use. In probiotics used in clinical trials can be generally considered as However, for possible such as infection in is and is review of available clinical trials found only limited data on the safety and clinical effects probiotic preparations to infant formulas, follow-up formulas, and special medical foods. There is no published for clinical benefit of infant formulas supplemented with probiotic No data are available on possible effects on intestinal and its effects on gastrointestinal and of such data be given the that bacteria during are more to the those during There are some data a benefit of some probiotic strains in infants and young children with The Committee that when adding probiotics to dietetic products for infants, only bacterial strains for which identity and genetic stability have been demonstrated by cultural and molecular methods and strains considered as generally when to the food in should be used. The content of viable bacteria in dietetic products must a to be and with to defined outcomes in clinical trials throughout the shelf-life of the The Committee that further evaluation of the safety and of probiotic bacteria in dietetic products for infants is strain to be used must be evaluated at the of for and and must be safety that should be are the effects on nutrient the possible of antibiotic the and effects on the and the risk of The Committee is that the available data are not to the safety of probiotics in and very young infants with infants with immunocompromised premature infants, and infants with The Committee that infant formulas with bacteria as probiotics should be marketed only if a evaluation of benefits and safety following the principles of standards has been Although the available data on the use of supplemented follow-on formulas is the Committee has effects of these products because are for use in infants 5 months, when there is a more an intestinal and a of to a variety of from the The addition of probiotic bacterial strains to infant foods for special medical and used under medical may be if a clinical benefit has been in adequate clinical even if a evaluation of all safety has not been for because of the limited number of patients to be with a the specific dietetic The Committee that there is that some probiotic preparations have benefits on health and benefits include a reduced of diarrhea, effects on diarrhea, of in vitro and animal studies on digestive and and from human studies on possible and therapeutic effects on atopic In of the for benefits on health that be achieved by the use of some probiotic on their evaluation are

StudyTop journalModerate

Effects of Probiotics on Gut Microbiota: An Overview

Preethi Chandrasekaran, Sabine Weiskirchen, Ralf Weiskirchen · International Journal of Molecular Sciences · 2024 · 299 citations

The role of probiotics in regulating intestinal flora to enhance host immunity has recently received widespread attention. Altering the human gut microbiota may increase the predisposition to several disease phenotypes such as gut inflammation and metabolic disorders. The intestinal microbiota converts dietary nutrients into metabolites that serve as biologically active molecules in modulating regulatory functions in the host. Probiotics, which are active microorganisms, play a versatile role in restoring the composition of the gut microbiota, helping to improve host immunity and prevent intestinal disease phenotypes. This comprehensive review provides firsthand information on the gut microbiota and their influence on human health, the dietary effects of diet on the gut microbiota, and how probiotics alter the composition and function of the human gut microbiota, along with their corresponding effects on host immunity in building a healthy intestine. We also discuss the implications of probiotics in some of the most important human diseases. In summary, probiotics play a significant role in regulating the gut microbiota, boosting overall immunity, increasing the abundance of beneficial bacteria, and helping ameliorate the symptoms of multiple diseases.

StudyModerate

Intestinal microbiota in functional bowel disorders: a Rome foundation report

Magnus Simrén, Giovanni Barbara, Harry J. Flint +6 more · Gut · 2012 · 921 citations

It is increasingly perceived that gut host-microbial interactions are important elements in the pathogenesis of functional gastrointestinal disorders (FGID). The most convincing evidence to date is the finding that functional dyspepsia and irritable bowel syndrome (IBS) may develop in predisposed individuals following a bout of infectious gastroenteritis. There has been a great deal of interest in the potential clinical and therapeutic implications of small intestinal bacterial overgrowth in IBS. However, this theory has generated much debate because the evidence is largely based on breath tests which have not been validated. The introduction of culture-independent molecular techniques provides a major advancement in our understanding of the microbial community in FGID. Results from 16S rRNA-based microbiota profiling approaches demonstrate both quantitative and qualitative changes of mucosal and faecal gut microbiota, particularly in IBS. Investigators are also starting to measure host-microbial interactions in IBS. The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses which increase epithelial permeability, activate nociceptive sensory pathways and dysregulate the enteric nervous system. While we await important insights in this field, the microbiota is already a therapeutic target. Existing controlled trials of dietary manipulation, prebiotics, probiotics, synbiotics and non-absorbable antibiotics are promising, although most are limited by suboptimal design and small sample size. In this article, the authors provide a critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID and evaluate the results of microbiota-directed interventions. The authors also provide clinical guidance on modulation of gut microbiota in IBS.

Meta-analysisHigh evidence score

The efficacy of probiotics, prebiotics, and synbiotics on anxiety, depression, and sleep: a systematic review and meta-analysis of randomized controlled trials

Jialin Zhang, Linqing Zhu, Qing Meng +2 more · BMC Psychiatry · 2025 · 3 citations

With the growing recognition of the limitations associated with conventional treatments for anxiety and depression, there has been increasing interest in alternative and adjunct therapies, particularly probiotics, prebiotics, and synbiotics. However, current research results regarding their efficacy in treating anxiety, depression, and sleep have been inconsistent. A systematic literature search for randomized controlled trials (RCTs) was conducted in PubMed, Web of Science, and Embase from inception to October 2023, updated in March 2025. The included studies involved individuals with anxiety and depression disorders, or chronic disease patients/healthy populations presenting with depressive or anxiety symptoms. Two researchers independently screened and extracted data. The Cochrane risk of bias tool was used to evaluate the quality of the included studies. Data synthesis and subgroup analyses were performed in Review Manager 5.3 and Stata 15.0 software. The anxiety, depression, and sleep scores were calculated by the standard mean difference (SMD) and 95% confidence intervals (CIs). A total of 72 RCTs were included (3,319 intervention and 2,778 control participants). Among these, researchers examined depression in 63 studies (2,880 and 2,493 participants) and anxiety in 49 studies (2,124 and 1,788 participants) using probiotics/prebiotics/synbiotics interventions, while 12 studies (411 and 378 participants) examined sleep using probiotic interventions. The meta-analysis demonstrated significant reductions compared to placebo in depression (SMD = − 0.53, 95% CI: −0.67 to − 0.39, Z = 7.33, P < 0.001) and anxiety (SMD = − 0.44, 95% CI: −0.59 to − 0.28, P < 0.001). Additionally, probiotics were shown to improve sleep quality (SMD = − 0.39, 95% CI: −0.53 to − 0.25, P < 0.001). Subgroup analyses indicated that both probiotics, prebiotics, and synbiotics independently alleviated anxiety and depression. The impact of probiotics varied by population, intervention duration, and probiotic types. These findings suggest that probiotics, prebiotics, and synbiotics offer promising adjunctive treatments for anxiety, depression, and sleep disturbances. However, given the high heterogeneity and limited methodological quality of the included studies, further large-scale and high-quality RCTs with long-term follow-up are needed to further validate these outcomes. The protocol was registered on PROSPERO (Registration number: CRD42024563862). Not applicable.

StudyLeading journalModerate

Unveiling the therapeutic symphony of probiotics, prebiotics, and postbiotics in gut-immune harmony

Pengjun Zhou, Chunlan Chen, Sandip Patil +1 more · Frontiers in Nutrition · 2024 · 171 citations

The gut microbiota and immune system interaction play a crucial role in maintaining overall health. Probiotics, prebiotics, and postbiotics have emerged as promising therapeutic approaches to positively influence this complex axis and enhance health outcomes. Probiotics, as live bacteria, promote the growth of immune cells, shape immune responses, and maintain gut barrier integrity. They modify the gut microbiota by fostering beneficial bacteria while suppressing harmful ones. Additionally, probiotics interact with the immune system, increasing immune cell activity and anti-inflammatory cytokine production. Prebiotics, as indigestible fibers, selectively nourish beneficial microorganisms in the gut, enhancing gut microbial diversity and activity. This, in turn, improves gut health and boosts immune responses while controlling inflammation through its immunomodulatory properties. Postbiotics, produced during probiotic fermentation, such as short-chain fatty acids and antimicrobial peptides, positively impact gut health and modulate immune responses. Ensuring quality control and standardization will be essential for successful clinical implementation of these interventions. Overall, understanding and harnessing the gut microbiota-immune system interplay offer promising avenues for improving digestive and immunological health.

StudyModerate

Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers

Kristin Schmidt, Philip J. Cowen, Catherine J. Harmer +3 more · Psychopharmacology · 2014 · 523 citations

RATIONALE: There is now compelling evidence for a link between enteric microbiota and brain function. The ingestion of probiotics modulates the processing of information that is strongly linked to anxiety and depression, and influences the neuroendocrine stress response. We have recently demonstrated that prebiotics (soluble fibres that augment the growth of indigenous microbiota) have significant neurobiological effects in rats, but their action in humans has not been reported. OBJECTIVES: The present study explored the effects of two prebiotics on the secretion of the stress hormone, cortisol and emotional processing in healthy volunteers. METHODS: Forty-five healthy volunteers received one of two prebiotics (fructooligosaccharides, FOS, or Bimuno®-galactooligosaccharides, B-GOS) or a placebo (maltodextrin) daily for 3 weeks. The salivary cortisol awakening response was sampled before and after prebiotic/placebo administration. On the final day of treatment, participants completed a computerised task battery assessing the processing of emotionally salient information. RESULTS: The salivary cortisol awakening response was significantly lower after B-GOS intake compared with placebo. Participants also showed decreased attentional vigilance to negative versus positive information in a dot-probe task after B-GOS compared to placebo intake. No effects were found after the administration of FOS. CONCLUSION: The suppression of the neuroendocrine stress response and the increase in the processing of positive versus negative attentional vigilance in subjects supplemented with B-GOS are consistent with previous findings of endocrine and anxiolytic effects of microbiota proliferation. Further studies are therefore needed to test the utility of B-GOS supplementation in the treatment of stress-related disorders.

StudyTop journalModerate

The potential application of probiotics and prebiotics for the prevention and treatment of COVID-19

Amin N. Olaimat, Iman Aolymat, Murad Al‐Holy +7 more · npj Science of Food · 2020 · 215 citations

COVID-19 is a pandemic disease caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This new viral infection was first identified in China in December 2019, and it has subsequently spread globally. The lack of a vaccine or curative treatment for COVID-19 necessitates a focus on other strategies to prevent and treat the infection. Probiotics consist of single or mixed cultures of live microorganisms that can beneficially affect the host by maintaining the intestinal or lung microbiota that play a major role in human health. At present, good scientific evidence exists to support the ability of probiotics to boost human immunity, thereby preventing colonization by pathogens and reducing the incidence and severity of infections. Herein, we present clinical studies of the use of probiotic supplementation to prevent or treat respiratory tract infections. These data lead to promising benefits of probiotics in reducing the risk of COVID-19. Further studies should be conducted to assess the ability of probiotics to combat COVID-19.

StudyLeading journalModerate

The Anti-Inflammatory and Curative Exponent of Probiotics: A Comprehensive and Authentic Ingredient for the Sustained Functioning of Major Human Organs

Muhammad Safiullah Virk, Muhammad Abdulrehman Virk, Yufeng He +9 more · Nutrients · 2024 · 110 citations

Several billion microorganisms reside in the gastrointestinal lumen, including viruses, bacteria, fungi, and yeast. Among them, probiotics were primarily used to cure digestive disorders such as intestinal infections and diarrhea; however, with a paradigm shift towards alleviating health through food, their importance is large. Moreover, recent studies have changed the perspective that probiotics prevent numerous ailments in the major organs. Probiotics primarily produce biologically active compounds targeting discommodious pathogens. This review demonstrates the implications of using probiotics from different genres to prevent and alleviate ailments in the primary human organs. The findings reveal that probiotics immediately activate anti-inflammatory mechanisms by producing anti-inflammatory cytokines such as interleukin (IL)-4, IL-10, IL-11, and IL-13, and hindering pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α by involving regulatory T cells (Tregs) and T helper cells (Th cells). Several strains of Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium longum, and Bifidobacterium breve have been listed among the probiotics that are excellent in alleviating various simple to complex ailments. Therefore, the importance of probiotics necessitates robust research to unveil the implications of probiotics, including the potency of strains, the optimal dosages, the combination of probiotics, their habitat in the host, the host response, and other pertinent factors.

StudyModerate

Next-Generation Probiotics as Novel Therapeutics for Improving Human Health: Current Trends and Future Perspectives

Mohamed E. Abouelela, Yosra A. Helmy · Microorganisms · 2024 · 187 citations

Next-generation probiotics (NGPs) represent an innovative group of beneficial bacteria that are currently undergoing research and development. NGPs are designed not only for conventional use as foods or dietary supplements but are also tailored for pharmaceutical applications. Research indicates that NGPs show therapeutic promise in addressing various chronic ailments. Offering multiple advantages over conventional probiotics, NGPs present opportunities for personalized probiotic therapies, involvement in synthetic biology and gene editing, participation in combination therapies, targeted delivery methods, and application in therapeutic settings. Our review discusses the potential therapeutic effect of the NGPs, covering diverse research trajectories for NGPs, including their identification, characterization, and targeted delivery. Furthermore, this review elucidates the influence of NGPs on critical aspects of human health, specifically, gut health, immune function, and broader health outcomes. Mechanistic insights encompass the production of bioactive compounds, competitive interactions with pathogenic bacteria, the modulation of immune cell activity, and the reinforcement of the gut barrier. What is noteworthy is that the current review points out the prevalent NGP strains and their diverse sources, providing a highlight for the comprehensive framework for understanding their potential applications and their future benefits in the domain of advanced therapeutics.

RCTHigh evidence score

Effect of probiotics on digestibility and immunity in infants

Lingli Xiao, Guodong Ding, Yifang Ding +8 more · Medicine · 2017 · 27 citations

The gastrointestinal (GI) tract of a fetus in utero is sterile but it becomes colonized with environmental microorganisms shortly after birth. Since the gut microbiota undergoes substantial changes in early life, healthy gut microflora is essential to an infant's gut health and immune system and probably also has an effect on overall health status in later life. Probiotics, defined as viable microbial preparations that have a beneficial effect on the health of the host, represent a rapidly expanding field. Although randomized controlled trials using probiotics in infants have shown promising results in the prevention and treatment of common diseases such as diarrhea and allergy, little is known about whether probiotics could offer benefits to healthy infants. We have designed a randomized controlled trial to test the hypothesis that an oral preparation of probiotics is superior to placebo in improving digestive and immune function in healthy infants.The trial will be a randomized, double-blind, placebo-controlled, 2-parallel-group study in Shanghai, China. After a 2-week run-in period, 200 exclusively formula-fed healthy infants aged 4 to 6 months will be randomly allocated to receive either a probiotic product containing Bifidobacterium infantis R0033, Bifidobacterium bifidum R0071, and Lactobacillus helveticus R0052 or an identical placebo once daily for 4 weeks and will be followed up for 8 weeks. The duration of the subject's participation will be 14 weeks, with a total of 5 visits: inclusion (Visit 1, Day 1), start of intervention (V2, D15), end of intervention (V3, D44), and follow-up (V4 and V5, D72 and D100). Stool and saliva samples will be collected at the first 3 visits to measure microbial populations and secretory immunoglobulin A (SIgA), respectively. Physical examination will be performed at each visit, and tolerance records will be completed 1 day prior to each visit. The primary endpoints will be the changes in the composition of fecal microbiota, particularly the Bifidobacterium bifidum population. The secondary endpoints will include the change in salivary SIgA level, growth parameters, digestive tolerance, and adverse events.An effective, practical, and acceptable probiotic intervention in manipulating the gut microbiota and boosting the immune system in formula-fed infants would represent a major clinical advance. The administration of probiotic supplementation or follow-on formula to infant may be associated with some clinic benefits.

StudyModerate

Probiotic Bifidobacterium breve in Improving Cognitive Functions of Older Adults with Suspected Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Trial

Jin‐zhong Xiao, Noriko Katsumata, François P. Bernier +6 more · Journal of Alzheimer s Disease · 2020 · 189 citations

BACKGROUND: Probiotics use has been associated with modulation of inflammation and considered as a possible intervention for CNS diseases such as mild cognitive impairment (MCI) and dementia. OBJECTIVE: We aimed to test the effect of the probiotic strain, Bifidobacterium breve A1 (MCC1274), to restore cognition in a physically healthy, suspected MCI population. METHODS: In this randomized, double-blind, placebo-controlled trial, 80 healthy older adults suffering from MCI were divided into two even groups to receive once daily either probiotic (B. breve A1, 2×1010 CFU) or placebo for 16 weeks using a computer-generated algorithm. Cognitive functions were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Japanese version of the MCI Screen (JMCIS) tests before and after the study as primary and secondary endpoints, respectively. RESULTS: 79 participants completed the study, and no adverse events were observed. RBANS total score was significantly improved in probiotic group compared with placebo (mean between-group difference 11.3 [95% CI 6.7 to 15.8]; p < 0.0001) after 16 weeks of consumption, in particular with significant improvement in domain scores of immediate memory, visuospatial/constructional, and delayed memory (p < 0.0001), in both intention-to-treat (ITT) analysis and per-protocol (PP) analysis. JMCIS score was also improved versus placebo in ITT analysis (p = 0.052) and PP analysis (p = 0.036). CONCLUSION: Study results indicate B. breve A1 is a safe and effective approach for improving memory functions of suspected MCI subjects.

RCTModerate

Probiotics: health benefits in the mouth.

Iva Stamatova, Jukka H. Meurman · PubMed · 2009 · 149 citations

Probiotics or health-beneficial bacteria have only recently been introduced in dentistry and oral medicine after years of successful use in mainly gastro-intestinal disorders. The concept of bacteriotherapy and use of health-beneficial micro-organisms to heal diseases or support immune function was first introduced in the beginning of the 20th century. Later the concept lead to the development of modem dairy industry and even today most probiotic strains are lactobacilli or bifidobacteria used in milk fermentation. The mechanisms of probiotic action are mainly unknown but the inter-microbial species interactions are supposed to play a key role in this together with their immuno-stimulatory effects. The introduction of probiotic bacteria in the mouth calls for ascertainment of their particular safety. Since acid production from sugar is detrimental to teeth, care must be taken not to select strains with high fermentation capacity. The first randomized controlled trials have nevertheless shown that probiotics may control dental caries in children due to their inhibitory action against cariogenic streptococci. Less evidence exists on their role in periodontal disease or oral yeast infections. Furthermore the best vehicles for oral probiotic applications need to be assessed. So far mainly dairy products have been investigated but other means such as probiotics in chewing gums or lozenges have also been studied. From the clinical practitioner's point of view direct recommendations for the use of probiotics cannot yet be given. However, scientific evidence so far indicates that probiotic therapy may be a reality also in dentistry and oral medicine in the future.

StudyModerate

Intestinal microbiota in human health and disease: the impact of probiotics

Jacoline Gerritsen, Hauke Smidt, Ger T. Rijkers +1 more · Genes & Nutrition · 2011 · 716 citations

The complex communities of microorganisms that colonise the human gastrointestinal tract play an important role in human health. The development of culture-independent molecular techniques has provided new insights in the composition and diversity of the intestinal microbiota. Here, we summarise the present state of the art on the intestinal microbiota with specific attention for the application of high-throughput functional microbiomic approaches to determine the contribution of the intestinal microbiota to human health. Moreover, we review the association between dysbiosis of the microbiota and both intestinal and extra-intestinal diseases. Finally, we discuss the potential of probiotic microorganism to modulate the intestinal microbiota and thereby contribute to health and well-being. The effects of probiotic consumption on the intestinal microbiota are addressed, as well as the development of tailor-made probiotics designed for specific aberrations that are associated with microbial dysbiosis.

StudyLeading journalModerate

Postbiotics: From emerging concept to application

Sunita Aggarwal, Vandana Sabharwal, Pragya Kaushik +3 more · Frontiers in Sustainable Food Systems · 2022 · 142 citations

The microbiome innovation has resulted in an umbrella term, postbiotics, which refers to non-viable microbial cells, metabolic byproducts and their microbial components released after lysis. Postbiotics, modulate immune response, gene expression, inhibit pathogen binding, maintain intestinal barriers, help in controlling carcinogenesis and pathogen infections. Postbiotics have antimicrobial, antioxidant, and immunomodulatory properties with favorable physiological, immunological, neuro-hormonal, regulatory and metabolic reactions. Consumption of postbiotics relieves symptoms of various diseases and viral infections such as SARS-CoV-2. Postbiotics can act as alternatives for pre-probiotic specially in immunosuppressed patients, children and premature neonates. Postbiotics are used to preserve and enhance nutritional properties of food, elimination of biofilms and skin conditioning in cosmetics. Postbiotics have numerous advantages over live bacteria with no risk of bacterial translocation from the gut to blood, acquisition of antibiotic resistance genes. The process of extraction, standardization, transport, and storage of postbiotic is more natural. Bioengineering techniques such as fermentation technology, high pressure etc., may be used for the synthesis of different postbiotics. Safety assessment and quality assurance of postbiotic is important as they may induce stomach discomfort, sepsis and/or toxic shock. Postbiotics are still in their infancy compared to pre- and pro- biotics but future research in this field may contribute to improved physiological functions and host health. The current review comprehensively summarizes new frontiers of research in postbiotics.

RCTHigh evidence score

Probiotics, Prebiotics, and Synbiotics

Lauri Jacobs · Journal of Pediatric Surgical Nursing · 2017 · 44 citations

For decades, scientists have known that the human body is host to trillions of commensal microbes, bacteria, yeast, and other organisms living in our bodies that confer benefits and cause no harm (Ciorba, 2012). The human gut is home to so many bacteria that bacterial cells outnumber host cells by 10 times. Different strains of bacteria offer different benefits. Bacteria may assist with digestion, immune function, and even production of some vitamins. Byproducts of bacterial fermentation may even provide 10% of a person's energy needs. Interestingly, poor nutrition, antibiotic use, and other factors may kill off these helpful bacteria causing a variety of problems. Only recently has the relationship between the microbiota of the gut and obesity been studied (Bäckhed et al., 2004). Some scientists argue that the fetus is sterile and that, through the process of natural childbirth, breastfeeding, and introduction of foods, the gut becomes populated with a healthy microbial flora (Dai & Walker, 1999). The types of bacteria living in the gut can be grouped into two subcategories: Bacteroidetes and Firmicutes. Observations in both animals and human research suggest that leaner individuals have more Bacteroidetes and a lower ratio of Firmicutes/Bacteroidetes than subjects who are affected by obesity (Sanchez, Panahi, & Tremblay, 2014). Studies also show that dietary changes influence these levels and that changing the ratio of these types of bacteria in the gut influences food intake, appetite, and body composition (Sanchez, Panahi, et al., 2014). Microbes that are purposely introduced to the gut for health benefits are called probiotics. This column provides a brief overview of what are probiotics, as well as related prebiotics and synbiotics, and how they affect obesity as well as safety, recommendations, and food sources. Probiotics are live microorganisms that are thought to impart health benefits to the host (National Center for Complimentary and Integrative Health, National Institutes of Health, 2016). They may be supplemented in the host via fermented foods or via dietary supplements. Probiotics must survive transit through the gastrointestinal tract and reach the intestine alive to impart these benefits (Ciorba, 2012). Fermented foods rich in probiotics include kefir (fermented yogurt drink), yogurt, miso, tempeh, and sauerkraut. Not all yogurts with live cultures are considered probiotic foods as many contain insufficient microbes to impart health benefits; on the other hand, some yogurt is specifically supplemented with additional bacteria and is deemed probiotic food. Prebiotics can be thought of as the “fertilizer” for the gut microbiota. Prebiotics are the nondigestible fibers or foods that promote the growth of the gut flora and help it to thrive. However, not all fibers are prebiotics. Examples of prebiotics are inulin and oligosaccharides (Niness, 1999). Foods naturally high in prebiotics include artichokes, onions, garlic, leeks, legumes, chicory root, peaches, nectarines, bananas, soy beans, asparagus, grapefruit, and watermelon. Chicory root and inulin are also used to increase fiber levels in processed foods such as high-fiber snack bars and pastas. Finally, synbiotics are combinations of probiotics and prebiotics that work together synergistically (Sáez-Lara, Robles-Sanchez, Ruiz-Ojeda, Plaza-Diaz, & Gil, 2016). In a 6-month, randomized controlled clinical trial of 225 volunteers in Finland, diets supplemented with a probiotic (Bifidobacterium animalis ssp. lactis 420) decreased body fat mass and body weight versus placebo (Stenman et al., 2016). Supplementing with a probiotic and a prebiotic synergistically decreased fat mass and increased lean body mass versus placebo. Participants showed positive improvement in waist circumference in those treated with probiotic (with or without prebiotic) and decreased energy intake in the probiotic groups (with or without prebiotic) after 6 months. Sanchez et al. in Canada randomized a group of adult men and women to receive a probiotic supplement (Lactobacillus rhamnosus CGMCC1.3724 [LPR]) with prebiotics (to help improve survival of the bacteria) twice daily versus a control group treated with placebo (Sanchez et al., 2014). Both groups were placed on energy-restricted diets (500 calories less than each individual's measured resting energy expenditure and predicted energy for activity). After 12 weeks of restriction, subjects were given a new meal plan for weight maintenance and were followed for an additional 12 weeks. Interestingly, the group as a whole did not lose weight, but there was a distinct difference in the men and women in the study group versus their counterparts in the control group. The women lost a significant amount of weight and kept losing weight in the subsequent 12 weeks after the probiotic was ceased versus female controls. In men, there was no significant difference between the control and treatment groups. This suggests a positive weight loss benefit for women taking this particular probiotic, with potentially lasting effects for sustained weight loss. Prebiotics alone have shown some positive effects promoting healthier weights. In another Canadian randomized controlled clinical trial, subjects were randomized to receive a placebo or prebiotic fiber (oligofructose) 21 g per day (Parnell & Reimer, 2009). After 12 weeks, participants had statistically significant weight loss in the treatment group, whereas controls gained weight. The weight loss was primarily fat loss and came from the trunk region of the body. Furthermore, the treatment group reduced their caloric intake and experienced decreases in ghrelin (a gut hormone that stimulates appetite) and increases in PYY (gut hormone that increases satiety). These studies along with numerous related research suggest promising effects with supplementing the diet with probiotics and prebiotics. Mechanisms proposed to explain these beneficial effects include decreasing insulin resistance, improved carbohydrate metabolism, increasing leptin levels, decreasing ghrelin levels, increasing PYY levels, and improving gut barrier function (Sáez-Lara et al., 2016; Stenman et al., 2016). In summary, probiotics and prebiotics, suggested in numerous studies, have a positive, albeit small, effect on improving body composition, although more research is needed to determine how they work and what barriers may keep them from working. Probiotics are generally considered as safe to use with most populations and have few complications. However, exceptions to this rule would include critically ill and immune-compromised patients and those with indwelling central vein catheters or possibly cardiac valve disease as there have been a few case reports of systemic infections and endocarditis (Doron & Snydman, 2015). Although prebiotics are safe to use in most populations, there are some individuals with certain gastrointestinal conditions that may not tolerate large amounts of prebiotic fibers. In addition, it is important to keep in mind that probiotics do not always colonize the gut; therefore, to see lasting effects, one needs to continue eating the probiotic foods or taking the probiotic supplements indefinitely (Ciorba, 2012), while eating a diet rich in prebiotic fibers to provide the “fertilizer” to help feed these microbes needed nutrients. Finally, probiotics are a dietary supplement, which means that they are not closely regulated by the Food and Drug Administration for quality and purity; the Food and Drug Administration relies on manufacturer's quality control testing. Eating a diet rich in probiotic foods and prebiotics may help you and your patients maintain a healthy gut microflora and a healthy weight.

StudyModerate

Lactobacilli and bifidobacteria ameliorate memory and learning deficits and oxidative stress in β-amyloid (1–42) injected rats

Somayeh Athari Nik Azm, Abolghassem Djazayeri, Majid Safa +5 more · Applied Physiology Nutrition and Metabolism · 2018 · 255 citations

The gastrointestinal microbiota affects brain function, including memory and learning. In this study we investigated the effects of probiotics on memory and oxidative stress biomarkers in an experimental model of Alzheimer’s disease. Sixty rats were randomly divided into 5 groups: control; control-probiotics, which received probiotics for 8 weeks; sham operation, which received an intrahippocampal injection of phosphate-buffered saline; Alzheimer, which received an intrahippocampal injection of β-amyloid (Aβ1–42); and Alzheimer-probiotics, which in addition to being injected with Aβ1–42, received 2 g (1 × 10 10 CFU/g) of probiotics (Lactobacillus acidophilus, L. fermentum, Bifidobacterium lactis, and B. longum) for 8 weeks. Memory and learning were measured using the Morris water maze, and oxidative stress biomarkers in the hippocampus were measured using ELISA kits. Morris water maze results indicated that compared with the Alzheimer group, the Alzheimer-probiotics group had significantly improved spatial memory, including shorter escape latency and travelled distance and greater time spent in the target quadrant. There was also improvement in oxidative stress biomarkers such as increased malondialdehyde levels and superoxide dismutase activity following the β-amyloid injection. Overall, it seems that probiotics play a role in improving memory deficit and inhibiting the pathological mechanisms of Alzheimer’s disease by modifying microbiota.

StudyModerate

Acne vulgaris, probiotics and the gut-brain-skin axis - back to the future?

Whitney P. Bowe, Alan Logan · Gut Pathogens · 2011 · 287 citations

Over 70 years have passed since dermatologists John H. Stokes and Donald M. Pillsbury first proposed a gastrointestinal mechanism for the overlap between depression, anxiety and skin conditions such as acne. Stokes and Pillsbury hypothesized that emotional states might alter the normal intestinal microflora, increase intestinal permeability and contribute to systemic inflammation. Among the remedies advocated by Stokes and Pillsbury were Lactobacillus acidophilus cultures. Many aspects of this gut-brain-skin unifying theory have recently been validated. The ability of the gut microbiota and oral probiotics to influence systemic inflammation, oxidative stress, glycemic control, tissue lipid content and even mood itself, may have important implications in acne. The intestinal microflora may also provide a twist to the developing diet and acne research. Here we provide a historical perspective to the contemporary investigations and clinical implications of the gut-brain-skin connection in acne.

RCTHigh evidence score

Probiotics for photoprotection

Audrey Guéniche, David Philippe, Batien Philippe +3 more · Dermato-Endocrinology · 2009 · 64 citations

Specific strains of probiotic, have been identified as beneficial to influence the composition and/or metabolic activity of the endogenous microbiota and some of these strains have been also shown to inhibit the growth of a wide range of enteropathogens. The first aim of using probiotics has been to improve the composition of the intestinal microbiota from a potentially harmful composition towards a composition that would be beneficial to the host.Beyond their capacity to influence positively the composition of the intestinal microbiota, several lines of evidence suggest that some probiotic bacteria can modulate the immune system both at the local and systemic levels thereby improving immune defense mechanisms and/or downregulate immune disorders such as allergies or intestinal inflammation.Skin reflects the general health status and aging. Different human trials widely suggest that probiotic supplementation might be useful in the management of atopic dermatitis. Based on these properties it appears that, beyond the gut, probiotics might exert their benefits at the skin level.In a randomized double blind placebo-controlled clinical trial, we investigated whether the probiotic bacteria Lactobacillus johnsonii NCC 533 (La1) could modulate the cutaneous immune homeostasis altered by solar-simulated UV exposure in humans. After, UV exposure to twice 1.5 MED, we demonstrated that La1 intake facilitated an earlier recovery of Epidermal cells allostimulatory function. Thus, this clinical data strengthen the assumption that certain probiotics can contribute to modulate skin immune system leading to the preservation of the skin homeostasis. Altogether the data affords the possibility of designing new strategies based on a nutritional approach for the prevention of UV-induced damaging effects.

RCTModerate

Probiotics and prebiotics in gastrointestinal disorders

Richard N. Fedorak, Karen Madsen · Current Opinion in Gastroenterology · 2004 · 149 citations

PURPOSE OF REVIEW: This review summarizes the clinical efficacy of probiotics and prebiotics in gastrointestinal disorders and examines the mechanisms of action related to their therapeutic effect. RECENT FINDINGS: The demonstration that immune and epithelial cells can discriminate between different microbial species has extended the known mechanism(s) of action of probiotics beyond simple barrier and antimicrobial effects. It has also confirmed that probiotic bacteria modulate mucosal and systemic immune activity and epithelial function. The progressive unraveling of these mechanisms of action has led to new credence for the use of probiotics and prebiotics in clinical medicine. Level I evidence now exists for the therapeutic use of probiotics in infectious diarrhea in children, recurrent Clostridium difficile-induced infections and postoperative pouchitis. Level II evidence is emerging for the use of probiotics in other gastrointestinal infections, prevention of postoperative bacterial translocation, irritable bowel syndrome, and in both ulcerative colitis and Crohn disease. Nevertheless, one consistent feature has emerged over the past year: Not all probiotic bacteria have similar therapeutic effects. Future clinical trials will need to incorporate this fact into trial planning and design. SUMMARY: The use of probiotics and prebiotics as therapeutic agents for gastrointestinal disorders is rapidly moving into the "mainstream." Mechanisms of action explain the therapeutic effects and randomized; controlled trials provide the necessary evidence for their incorporation into the therapeutic armamentarium.

StudyLeading journalModerate

The Preventive and Curative Effects of Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98 on Immobilization Stress-Induced Anxiety/Depression and Colitis in Mice

Hyo‐Min Jang, Kyung‐Eon Lee, Dong‐Hyun Kim · Nutrients · 2019 · 201 citations

The gut dysbiosis by stressors such as immobilization deteriorates psychiatric disorders through microbiota-gut-brain axis activation. To understand whether probiotics could simultaneously alleviate anxiety/depression and colitis, we examined their effects on immobilization stress (IS)-induced anxiety/depression and colitis in mice. The probiotics Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98 were isolated from healthy human feces. Mice with anxiety/depression and colitis were prepared by IS treatment. NK33 and NK98 potently suppressed NF-κB activation in lipopolysaccharide (LPS)-induced BV-2 cells. Treatment with NK33 and/or NK98, which were orally gavaged in mice before or after IS treatment, significantly suppressed the occurrence and development of anxiety/depression, infiltration of Iba1+ and LPS+/CD11b+ cells (activated microglia) into the hippocampus, and corticosterone, IL-6, and LPS levels in the blood. Furthermore, they induced hippocampal BDNF expression while NF-κB activation was suppressed. NK33 and/or NK98 treatments suppressed IS-induced colon shortening, myeloperoxidase activity, infiltration of CD11b+/CD11c+ cells, and IL-6 expression in the colon. Their treatments also suppressed the IS-induced fecal Proteobacteria population and excessive LPS production. They also induced BDNF expression in LPS-induced SH-SY5Y cells in vitro. In conclusion, NK33 and NK98 synergistically alleviated the occurrence and development of anxiety/depression and colitis through the regulation of gut immune responses and microbiota composition.

StudyModerate

Probiotics-induced changes in gut microbial composition and its effects on cognitive performance after stress: exploratory analyses

Mirjam Bloemendaal, Joanna Szopinska-Tokov, Clara Belzer +6 more · Translational Psychiatry · 2021 · 121 citations

Abstract Stress negatively affects cognitive performance. Probiotics remediate somatic and behavioral stress responses, hypothetically by acting on the gut microbiota. Here, in exploratory analyses, we assessed gut microbial alterations after 28-days supplementation of multi-strain probiotics (EcologicBarrier consisting of Lactobacilli , Lactococci , and Bifidobacteria in healthy, female subjects (probiotics group n = 27, placebo group n = 29). In an identical pre-session and post-session, subjects performed a working memory task before and after an acute stress intervention. Global gut microbial beta diversity changed over time, but we were not able to detect differences between intervention groups. At the taxonomic level, Time by Intervention interactions were not significant after multiple comparison correction; the relative abundance of eight genera in the probiotics group was higher (uncorrected) relative to the placebo group: Butyricimonas, Parabacteroides, Alistipes, Christensenellaceae_R-7_group, Family_XIII_AD3011_group, Ruminococcaceae_UCG-003, Ruminococcaceae_UCG-005 , and Ruminococcaceae_UCG-010 . In a second analysis step, association analyses were done only within this selection of microbial genera, revealing the probiotics-induced change in genus Ruminococcaceae_UCG-003 was significantly associated with probiotics’ effect on stress-induced working memory changes ( r spearman (27) = 0.565; pFDR = 0.014) in the probiotics group only and independent of potential confounders (i.e., age, BMI, and baseline dietary fiber intake). That is subjects with a higher increase in Ruminococcaceae_UCG-003 abundance after probiotics were also more protected from negative effects of stress on working memory after probiotic supplementation. The bacterial taxa showing an increase in relative abundance in the probiotics group are plant fiber degrading bacteria and produce short-chain fatty acids that are known for their beneficial effect on gut and brain health, e.g., maintaining intestinal-barrier and blood–brain-barrier integrity. This study shows that gut microbial alterations, modulated through probiotics use, are related to improved cognitive performance in acute stress circumstances.

StudyLeading journalModerate

Probiotic mediated intestinal microbiota and improved performance, egg quality and ovarian immune function of laying hens at different laying stage

Hengyong Xu, Yuxiang Lu, Dan Li +11 more · Frontiers in Microbiology · 2023 · 69 citations

In order to investigate the effects of dietary probiotics supplementation on laying performance, egg quality, serum hormone levels, immunity, antioxidant, and gut microbiota of layers at different laying stages, a total of 168 Tianfu green shell laying hens (28-day-old) were randomly divided into 2 treatments: a non-supplemented control diet (NC), and diet supplemented with 10 g/kg of probiotics, respectively. Each treatment had 6 replicates with 14 hens per replicate. The feeding trial lasted for 54 weeks. The results showed that the supplementation of probiotics significantly increased the average egg weight, improved egg quality ( p &amp;lt; 0.05) and ovarian development. Meanwhile, probiotics increased the serum hormone levels of E 2 and FSH, and antioxidant indices T-AOC and T-SOD ( p &amp;lt; 0.05) of laying hens at different laying stages ( p &amp;lt; 0.05), decreased the expression of proinflammatory factors including IL-1, IL-6 and TNF- α ( p &amp;lt; 0.05). Furthermore, using 16S rRNA sequencing, we observed that the addition of probiotics increased the distribution of Firmicutes , Bacteroidota and Synergistota at early laying period. Meanwhile, Bacteroidota , Actinobacteriota , Verrucomicrobiota and Deferribacterota showed an increasing trend at the peak of egg production. The relative abundance of Firmicutes , Desulfobacterota and Actinobacteriota were significantly increased at the late laying period. Moreover, PICRUSt2 and BugBase analysis revealed that at the late laying period, the probiotics supplementation not only enriched many significant gene clusters of the metabolism of terpenoids and polyketide, genetic information processing, enzyme families, translation, transcription, replication and repair, and nucleotide metabolism, but also decreased the proportion of potential pathogenic bacteria. To sum up, these data show that the addition of probiotics not only improves the performance, egg quality, ovarian development and immune function of laying hens at different laying period, but also improves the gut microbiota of layers, thus enhances production efficiency.

StudyTop journalModerate

Beneficial Properties of Probiotics

Lye Huey Shi, Balakrishnan Kunasundari, Kokila Thiagarajah +2 more · Tropical Life Sciences Research · 2016 · 224 citations

Probiotics are live microorganisms that can be found in fermented foods and cultured milk, and are widely used for the preparation of infant food. They are well-known as “health friendly bacteria”, which exhibit various health beneficial properties such as prevention of bowel diseases, improving the immune system, for lactose intolerance and intestinal microbial balance, exhibiting antihypercholesterolemic and antihypertensive effects, alleviation of postmenopausal disorders, and reducing traveller’s diarrhoea. Recent studies have also been focused on their uses in treating skin and oral diseases. In addition to that, modulation of the gut-brain by probiotics has been suggested as a novel therapeutic solution for anxiety and depression. Thus, this review discusses on the current probiotics-based products in Malaysia, criteria for selection of probiotics, and evidences obtained from past studies on how probiotics have been used in preventing intestinal disorders via improving the immune system, acting as an antihypercholesterolemic factor, improving oral and dermal health, and performing as anti-anxiety and anti-depressive agents. Probiotik ialah mikroorganisma hidup yang boleh didapati dalam makanan fermentasi dan susu kultur, dan digunakan secara meluas dalam penyediaan makanan bayi. Probiotik dikenali sebagai “bakteria baik” yang memiliki pelbagai manfaat untuk kesihatan seperti pencegahan penyakit usus, peningkatan sistem imun, intoleransi laktosa dan keseimbangan mikrob usus, menunjukkan kesan antihiperkolesterolemik dan antihipertensi, meredakan gangguan menopaus, dan mengurangkan cirit-birit pengembara. Kajian baru-baru ini juga telah memberi tumpuan kepada kegunaan probiotik dalam merawati penyakit kulit dan mulut. Di samping itu, modulasi paksi gut-otak dengan probiotik telah dicadangkan sebagai penyelesaian terapeutik baru bagi gejala kebimbangan dan kemurungan. Oleh itu, kajian ini membincangkan mengenai produk-produk semasa yang mengandungi probiotik di Malaysia, kriteria pemilihan probiotik, dan bukti-bukti yang diperolehi daripada kajian lepas tentang bagaimana probiotik telah digunakan untuk mencegah gangguan usus melalui peningkatan sistem imun, bertindak sebagai faktor antihiperkolesterolemik, meningkatkan kesihatan mulut dan kulit, dan berperanan sebagai ejen anti-kebimbangan dan anti-kemurungan.

StudyModerate

Diet-Induced Gut Dysbiosis and Leaky Gut Syndrome

Yu-Rim Chae, Yu Ra Lee, Young‐Soo Kim +1 more · Journal of Microbiology and Biotechnology · 2024 · 77 citations

Chronic gut inflammation promotes the development of metabolic diseases such as obesity. There is growing evidence which suggests that dysbiosis in gut microbiota and metabolites disrupt the integrity of the intestinal barrier and significantly impact the level of inflammation in various tissues, including the liver and adipose tissues. Moreover, dietary sources are connected to the development of leaky gut syndrome through their interaction with the gut microbiota. This review examines the effects of these factors on intestinal microorganisms and the communication pathways between the gut-liver and gut-brain axis. The consumption of diets rich in fats and carbohydrates has been found to weaken the adherence of tight junction proteins in the gastrointestinal tract. Consequently, this allows endotoxins, such as lipopolysaccharides produced by detrimental bacteria, to permeate through portal veins, leading to metabolic endotoxemia and alterations in the gut microbiome composition with reduced production of metabolites, such as short-chain fatty acids. However, the precise correlation between gut microbiota and alternative sweeteners remains uncertain, necessitating further investigation. This study highlights the significance of exploring the impact of diet on gut microbiota and the underlying mechanisms in the gut-liver and gut-brain axis. Nevertheless, limited research on the gut-liver axis poses challenges in comprehending the intricate connections between diet and the gut-brain axis. This underscores the need for comprehensive studies to elucidate the intricate gut-brain mechanisms underlying intestinal health and microbiota.

StudyModerate

Probiotics, Prebiotics, Synbiotics, and Fermented Foods as Potential Biotics in Nutrition Improving Health via Microbiome-Gut-Brain Axis

Divakar Dahiya, Poonam Singh Nee Nigam · Fermentation · 2022 · 142 citations

Biological, social, and psychological practices greatly affect the dietary intake of people; as a result, health-related complexities occur. Functional food and supplements have become popular due to their nutraceutical benefits, which make different choices of fermented food and beverages available to people. This review describes the characteristics of probiotics, prebiotics, post- and paraprobiotics, and their role in nutrition and in the sustainability of health. Currently, several synbiotic supplements have attracted consumers in the nutraceutical market to offer a number of health benefits, which are complementary mixtures of selected characterized probiotic cultures and prebiotic substrates. Traditional fermented foods consumed in different cultures are different than probiotics and symbiotic preparations, though these could be considered potential biotics in nutrition. Fermented foods are part of a staple diet in several countries and are cost-effective due to their preparation using seasonal raw materials available from local agriculture practices. Intake of all biotics discussed in this article is intended to improve the population of beneficial microbiota in the gut, which has proved important for the microbiome–gut–brain axis, influencing the activity of vagus nerve.

StudyModerate

Para‐psychobiotic <i>Lactobacillus gasseri</i> <scp>CP</scp> 2305 ameliorates stress‐related symptoms and sleep quality

Kensei Nishida, Daisuke Sawada, Tomoko Kawai +3 more · Journal of Applied Microbiology · 2017 · 152 citations

AIMS: To confirm the stress-relieving effects of heat-inactivated, enteric-colonizing Lactobacillus gasseri CP2305 (paraprobiotic CP2305) in medical students taking a cadaver dissection course. METHODS AND RESULTS: Healthy students (21 males and 11 females) took paraprobiotic CP2305 daily for 5 weeks during a cadaver dissection course. The General Health Questionnaire and the Pittsburgh Sleep Quality Index were employed to assess stress-related somatic symptoms and sleep quality respectively. The aggravation of stress-associated somatic symptoms was observed in female students (P = 0·029). Sleep quality was improved in the paraprobiotic CP2305 group (P = 0·038), particularly in men (P = 0·004). Among men, paraprobiotic CP2305 shortened sleep latency (P = 0·035) and increased sleep duration (P = 0·048). Diarrhoea-like symptoms were also effectively controlled with CP2305 (P = 0·005) in men. Thus, we observed sex-related differences in the effects of paraprobiotic CP2305. In addition, CP2305 affected the growth of faecal Bacteroides vulgatus and Dorea longicatena, which are involved in intestinal inflammation. CONCLUSIONS: CP2305 is a potential paraprobiotic that regulates stress responses, and its beneficial effects may depend on specific cell component(s). SIGNIFICANCE AND IMPACT OF THE STUDY: This study characterizes the effects of a stress-relieving para-psychobiotic in humans.

StudyLeading journalModerate

Exploring the Potential of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 as Promising Psychobiotics Using SHIME

Fellipe Lopes de Oliveira, Mateus Kawata Salgaço, Marina Toscano de Oliveira +5 more · Nutrients · 2023 · 49 citations

Psychobiotics are probiotics that have the characteristics of modulating central nervous system (CNS) functions or reconciled actions by the gut–brain axis (GBA) through neural, humoral and metabolic pathways to improve gastrointestinal activity as well as anxiolytic and even antidepressant abilities. The aim of this work was to evaluate the effect of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 on the gut microbiota of mildly anxious adults using SHIME®. The protocol included a one-week control period and two weeks of treatment with L. helveticus R0052 and B. longum R0175. Ammonia (NH4+), short chain fatty acids (SCFAs), gamma-aminobutyric acid (GABA), cytokines and microbiota composition were determined. Probiotic strains decreased significantly throughout the gastric phase. The highest survival rates were exhibited by L. helveticus R0052 (81.58%; 77.22%) after the gastric and intestinal phase when compared to B. longum (68.80%; 64.64%). At the genus level, a taxonomic assignment performed in the ascending colon in the SHIME® model showed that probiotics (7 and 14 days) significantly (p &lt; 0.005) increased the abundance of Lactobacillus and Olsenella and significantly decreased Lachnospira and Escheria-Shigella. The probiotic treatment (7 and 14 days) decreased (p &lt; 0.001) NH4+ production when compared to the control period. For SCFAs, we observed after probiotic treatment (14 days) an increase (p &lt; 0.001) in acetic acid production and total SCFAs when compared to the control period. Probiotic treatment increased (p &lt; 0.001) the secretion of anti-inflammatory (IL-6 and IL-10) and decreased (p &lt; 0.001) pro-inflammatory cytokines (TNF-alpha) when compared to the control period. The gut–brain axis plays an important role in the gut microbiota, producing SCFAs and GABA, stimulating the production of anti-anxiety homeostasis. The signature of the microbiota in anxiety disorders provides a promising direction for the prevention of mental illness and opens a new perspective for using the psychobiotic as a main actor of therapeutic targets.

StudyModerate

Effect of Probiotic Supplementation on Schizophrenia Symptoms and Association With Gastrointestinal Functioning

Faith Dickerson, Cassie Stallings, Andrea Origoni +6 more · The Primary Care Companion For CNS Disorders · 2014 · 166 citations

Article Abstract Objective: A range of immune system abnormalities have been associated with schizophrenia. Probiotic compounds modulate the immune response and offer a potential treatment strategy for schizophrenia. Probiotic compounds have also been observed to improve gastrointestinal dysfunction, which is a common problem in individuals with schizophrenia. We performed a randomized, double-blind, placebo-controlled trial to examine whether probiotic supplementation can reduce symptom severity in patients with schizophrenia receiving antipsychotic treatment and also whether probiotics are associated with bowel functioning. Methods: Outpatients with schizophrenia (N = 65) meeting DSM-IV criteria and with at least moderately severe psychotic symptoms were enrolled in the study from December 2010-August 2012. Following a 2-week placebo run-in period, patients were randomly assigned to 14 weeks of double-blind adjunctive probiotic (combined Lactobacillus rhamnosus strain GG and Bifidobacterium animalis subsp. lactis strain Bb12) or placebo therapy. Psychiatric symptoms were assessed biweekly with the Positive and Negative Syndrome Scale (PANSS), and patients were queried weekly about their gastrointestinal functioning. Results: Repeated-measures analysis of variance showed no significant differences in the PANSS total score between probiotic and placebo supplementation (F = 1.28, P = .25). However, patients in the probiotic group were less likely to develop severe bowel difficulty over the course of the trial (hazard ratio = 0.23; 95% CI, 0.09-0.61, P = .003). Conclusions: Probiotic supplementation may help prevent a common somatic symptom associated with schizophrenia. Trial Registration: ClinicalTrials.gov identifier: NCT01242371 Prim Care Companion CNS Disord 2014;16(1):doi:10.4088/PCC.13m01579 © Copyright 2014 Physicians Postgraduate Press, Inc. Submitted: September 6, 2013; accepted October 18, 2013. Published online: February 13, 2014. Corresponding author: Faith B. Dickerson, PhD, Stanley Research Program at Sheppard Pratt, Sheppard Pratt Health System, 6501 North Charles St, Baltimore, MD 21204 (fdickerson@sheppardpratt.org).

RCTHigh evidence score

Effect of Probiotic Supplementation on Maternal Depression, Anxiety and Attachment in Gestational Diabetes by Improving Mediterranean Diet Quality: A Randomized Controlled Trial

Fatma Bengü Kuyulu Bozdoğan, Seray Kabaran, Aybala Tazeoğlu · Clinical and Experimental Obstetrics & Gynecology · 2024 · 3 citations

Background: Factors such as the coronavirus disease 2019 (COVID-19) pandemic quarantine, economic decline, and unemployment have an impact on mental health, and have made mental illnesses an important public health problem worldwide. According to the World Health Organization, depression is currently the fourth reason of the global burden of diseas. Evidence shows that women with gestational diabetes (GDM) are at higher risk of developing depression during pregnancy. Despite extensive research carried out by the probiotic industry in recent years, there is a lack of consensus on the available evidence on how best to use probiotics in mental health. Considering the impact of probiotics on mental health, our study aimed to answer the question of whether probiotic supplementation is effective on depression and anxiety in women with gestational diabetes. Methods: In this randomized controlled study with an allocation ratio of 1:1, the participants were divided into two groups: control group, received standard diet compatible with Mediterranean diet (MD) while the probiotic supplementation group received both the standard diet compatible with MD and probiotic supplementation (Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum, Bifidobacterium longum and Enterococcus faecium). The participants’ sociodemographic data, medical history, pregnancy data, and adherence to the Mediterranean diet at 24 and 36 weeks of pregnancy were recorded. Edinburgh Postnatal Depression Scale (EPDS), Pregnancy-Related Anxiety Scale (PrAS), and Maternal Antenatal Attachment Scale (MAAS) scales were used. Two-way repeated measures analysis of variance was used to examine group and time effects and group-time interactions. Additionally, sleep problems, stressful events, and sedentary physical activity were added as exclusion criteria to optimize the impact of potential problems on depression. Results: In the control and probiotic groups, anxiety scores at 36 weeks of gestation were found to be 16.53 ± 3.49 and 16.27 ± 3.62, respectively (p = 0.771). Maternal attachment scores at 36 weeks of gestation were found to be 67.39 ± 7.56 and 69.29 ± 5.89 in the control and probiotic groups, respectively (p = 0.266). Depression (8.24 ± 2.48; 8.56 ± 2.75, p = 0.627) and anxiety scores during pregnancy and weight gain (12.80 ± 2.97 and 12.07 ± 2.41, p = 0.284) were lower in the probiotic supplementation group at 36 weeks of gestation compared to the control group. The Mediterranean diet score was higher in the probiotic supplement group (33.64 ± 4.92) compared to the control group (31.97 ± 5.18) at week 36. Multiple regression analysis was performed to examine the prediction of depression risk based on the scores obtained from the Med-diet (Mediterranean diet) scale. Accordingly, EPDS (β = –0.57, p = 0.001), PrAS (β = –0.32, p = 0.004), and MAAS (β = 0.78, p = 0.003) significantly predicted the Med-diet score. A one-unit improvement in the Med-diet score resulted in a decrease of 0.57 units in depression, a decrease of 0.3 units in anxiety and an increase of 0.78 units in maternal attachment in both groups. Conclusions: In GDM, the Mediterranean diet quality had a significant negative relationship with depression and anxiety, and a positive relationship with maternal attachment. The group receiving probiotic supplementation had lower scores for depression and anxiety and lower gestational weight gain. However, the Mediterranean diet score was higher in the probiotic group at week 36. Clinical Trial Registration: Registered under ISRCTN registry (https://www.isrctn.com/ISRCTN96215615) identifier no. ISRCTN96215615.

StudyLeading journalModerate

The Efficacy, Safety, and Tolerability of Probiotics on Depression: Clinical Results From an Open-Label Pilot Study

Caroline Wallace, Roumen Milev · Frontiers in Psychiatry · 2021 · 113 citations

Background: A growing body of research has shown that consumption of probiotics can improve symptoms associated with mood and anxiety disorders through activity of the gut-brain axis. However, the effects of probiotics have yet to be tested in a clinical sample of treatment-naïve patients diagnosed with Major Depressive Disorder (MDD). The aim of this 8-week, open-label pilot study is to examine changes in depressive symptoms before and after the introduction of a probiotic supplement in 10 treatment-naïve MDD patients and to provide data on the feasibility of conducting a larger double-blind, randomized, placebo-controlled trial in the same patient population. Here we report on the clinical outcome measures of the study. Methods: Participants recruited from the community in Kingston, Ontario, Canada consumed a probiotic supplement containing Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (CEREBIOME ® ) at a dose of 3 × 10 9 CFU once per day for 8 weeks. Clinical symptoms of depression were measured using a validated battery of clinical scales and self-report questionnaires (CAN-BIND protocol). Data was collected at baseline, week 4, and week 8. Results: Significant improvements in affective clinical symptoms were observed at week 4 and were sustained at week 8. Significant improvements in subjective sleep quality were observed by week 8. No side effects or adverse effects associated with the probiotic supplement were observed. Conclusions: The findings from this study support the existing evidence in this emerging field for probiotics having a role in alleviating symptoms of depression in treatment-naïve, moderately depressed patients and indicate that the probiotic supplement is safe and well-tolerated in this population. However, further comprehensive studies are required to draw conclusions.

StudyLeading journalModerate

Xylo-oligosaccharides alone or in synbiotic combination with<i>Bifidobacterium animalis</i>subsp.<i>lactis</i>induce bifidogenesis and modulate markers of immune function in healthy adults: a double-blind, placebo-controlled, randomised, factorial cross-over study

Caroline E. Childs, Henna Röytiö, Esa Alhoniemi +10 more · British Journal Of Nutrition · 2014 · 156 citations

Prebiotics, probiotics and synbiotics are dietary ingredients with the potential to influence health and mucosal and systemic immune function by altering the composition of the gut microbiota. In the present study, a candidate prebiotic (xylo-oligosaccharide, XOS, 8 g/d), probiotic (Bifidobacterium animalis subsp. lactis Bi-07, 109 colony-forming units (CFU)/d) or synbiotic (8 g XOS+109 CFU Bi-07/d) was given to healthy adults (25-65 years) for 21 d. The aim was to identify the effect of the supplements on bowel habits, self-reported mood, composition of the gut microbiota, blood lipid concentrations and immune function. XOS supplementation increased mean bowel movements per d (P= 0·009), but did not alter the symptoms of bloating, abdominal pain or flatulence or the incidence of any reported adverse events compared with maltodextrin supplementation. XOS supplementation significantly increased participant-reported vitality (P= 0·003) and happiness (P= 0·034). Lowest reported use of analgesics was observed during the XOS+Bi-07 supplementation period (P= 0·004). XOS supplementation significantly increased faecal bifidobacterial counts (P= 0·008) and fasting plasma HDL concentrations (P= 0·005). Bi-07 supplementation significantly increased faecal B. lactis content (P= 0·007), lowered lipopolysaccharide-stimulated IL-4 secretion in whole-blood cultures (P= 0·035) and salivary IgA content (P= 0·040) and increased IL-6 secretion (P= 0·009). XOS supplementation resulted in lower expression of CD16/56 on natural killer T cells (P= 0·027) and lower IL-10 secretion (P= 0·049), while XOS and Bi-07 supplementation reduced the expression of CD19 on B cells (XOS × Bi-07, P= 0·009). The present study demonstrates that XOS induce bifidogenesis, improve aspects of the plasma lipid profile and modulate the markers of immune function in healthy adults. The provision of XOS+Bi-07 as a synbiotic may confer further benefits due to the discrete effects of Bi-07 on the gut microbiota and markers of immune function.

StudyLeading journalModerate

Combination of <i>Lactobacillus helveticus R0052</i> and <i>Bifidobacterium longum R0175</i> reduces post-myocardial infarction depression symptoms and restores intestinal permeability in a rat model

Jessica Arseneault-Bréard, Isabelle Rondeau, Gilbert Kim +4 more · British Journal Of Nutrition · 2011 · 203 citations

Myocardial infarction (MI) in rats is accompanied by apoptosis in the limbic system and a behavioural syndrome similar to models of depression. We have already shown that probiotics can reduce post-MI apoptosis and designed the present study to determine if probiotics can also prevent post-MI depressive behaviour. We also tested the hypothesis that probiotics achieve their central effects through changes in the intestinal barrier. MI was induced in anaesthetised rats via 40-min transient occlusion of the left anterior coronary artery. Sham rats underwent the same surgical procedure without actual coronary occlusion. For 7 d before MI and between the seventh post-MI day and euthanasia, half the MI and sham rats were given one billion live bacterial cells of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 per d dissolved in water, while the remaining animals received only the vehicle (maltodextrin). Depressive behaviour was evaluated 2 weeks post-MI in social interaction, forced swimming and passive avoidance step-down tests. Intestinal permeability was evaluated by oral administration with fluorescein isothiocyanate-dextran, 4 h before euthanasia. MI rats displayed less social interaction and impaired performance in the forced swimming and passive avoidance step-down tests compared to the sham controls (P < 0·05). Probiotics reversed the behavioural effects of MI (P < 0·05), but did not alter the behaviour of sham rats. Intestinal permeability was increased in MI rats and reversed by probiotics. In conclusion, L. helveticus R0052 and B. longum R0175 combination interferes with the development of post-MI depressive behaviour and restores intestinal barrier integrity in MI rats.

StudyTop journalModerate

Dietary Prebiotics and Bioactive Milk Fractions Improve NREM Sleep, Enhance REM Sleep Rebound and Attenuate the Stress-Induced Decrease in Diurnal Temperature and Gut Microbial Alpha Diversity

Robert S. Thompson, Rachel Roller, Agnieszka Mika +5 more · Frontiers in Behavioral Neuroscience · 2017 · 111 citations

Severe, repeated or chronic stress produces negative health outcomes including disruptions of the sleep/wake cycle and gut microbial dysbiosis. Diets rich in prebiotics and glycoproteins impact the gut microbiota and may increase gut microbial species that reduce the impact of stress. This experiment tested the hypothesis that consumption of dietary prebiotics, lactoferrin, and milk fat globule membrane will reduce the negative physiological impacts of stress. Male F344 rats, postnatal day (PND) 24, received a diet with prebiotics, lactoferrin, and milk fat globule membrane (test) or a calorically matched control diet. Fecal samples were collected on PND 35/70/91 for 16S rRNA sequencing to examine microbial composition and, in a subset of rats; Lactobacillus rhamnosus was measured using selective culture. On PND 59, biotelemetry devices were implanted to record sleep/wake EEG. Rats were exposed to an acute stressor (100, 1.5mA, tail shocks) on PND 87 and recordings continued until PND 94. Test diet, compared to control diet, increased fecal Lactobacillus rhamnosus colony forming units, facilitated NREM sleep consolidation (PND 71/72) and enhanced REM sleep rebound after stressor exposure (PND 87). Rats fed control diet had stress-induced reductions in alpha diversity and diurnal amplitude of temperature, which were attenuated by the test diet (PND 91). Stepwise multiple regression analysis revealed a significant linear relationship between early-life Deferribacteres (PND 35) and longer NREM sleep episodes (PND 71/72). A diet containing prebiotics, Lf and MFGM enhanced sleep quality, which was related to changes in gut bacteria and modulated the impact of stress on sleep, diurnal rhythms and the gut microbiota.