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Background There is substantial demand for gut health products incorporating probiotics and prebiotics. They are being delivered as ingredients in an increasing range of different product formulations. While new delivery matrices are assessed for their potential impact on cell viability and prebiotic degradation, it is unknown whether they should be expected to independently alter the clinical effect of a given probiotic and prebiotic. Scope and Approach We provide an overview of preclinical and clinical data to examine the degree to which probiotic and prebiotic efficacy may be altered by processing and incorporation into various delivery matrices. We also consider the impact of inter-individual host factors on product efficacy. We further review regulatory positions across the globe on substantiation of prebiotic and probiotic efficacy in the final product format. Key Findings and Conclusions In vitro data suggest that the delivery matrix may interact with prebiotic and probiotic functions via various physicochemical interactions with molecular and cellular structures and changes in cellular expression. However, direct evidence to suggest these changes have a significant in vivo impact is very limited. Indeed, meta-analyses suggest an elasticity robustness of effect across delivery matrices. Regulatory expectations vary among regions, but scope typically exists for adequate scientific justification to translate probiotic or prebiotic evidence across product formats. Early evidence suggests host factors such as diet, health and microbiome status are likely to play an important role in an individual’s response to a given probiotic and prebiotic.

An expert panel was convened in September 2019 by The International Scientific Association for Probiotics and Prebiotics (ISAPP) to develop a definition for fermented foods and to describe their role in the human diet. Although these foods have been consumed for thousands of years, they are receiving increased attention among biologists, nutritionists, technologists, clinicians and consumers. Despite this interest, inconsistencies related to the use of the term ‘fermented’ led the panel to define fermented foods and beverages as “foods made through desired microbial growth and enzymatic conversions of food components”. This definition, encompassing the many varieties of fermented foods, is intended to clarify what is (and is not) a fermented food. The distinction between fermented foods and probiotics is further clarified. The panel also addressed the current state of knowledge on the safety, risks and health benefits, including an assessment of the nutritional attributes and a mechanistic rationale for how fermented foods could improve gastrointestinal and general health. The latest advancements in our understanding of the microbial ecology and systems biology of these foods were discussed. Finally, the panel reviewed how fermented foods are regulated and discussed efforts to include them as a separate category in national dietary guidelines., Although fermented foods have been consumed for thousands of years, a clear definition has been lacking. This Consensus Statement outlines a definition for the term ‘fermented foods’ as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in September 2019.

The collective findings from human microbiome research, randomized controlled trials on specific microbes (i.e., probiotics), and associative studies of fermented dairy consumption provide evidence for the beneficial effects of the regular consumption of safe live microbes. To test the hypothesis that the inclusion of safe, live microbes in the diet supports and improves health, we propose assessment of the types and evidentiary quality of the data available on microbe intake, including the assembly and evaluation of evidence available from dietary databases. Such an analysis would help to identify gaps in the evidence needed to test this hypothesis, which can then be used to formulate and direct initiatives focused on prospective and randomized controlled trials on live microbe consumption. Outcomes will establish whether or not the evidence exists, or can be generated, to support the establishment of dietary recommendations for live microbes.

A history of safe use is a backbone of safety assessments for many current probiotic species, however, there is no global harmonization regarding requirements for establishing probiotic safety for use in foods and supplements. As probiotic manufacturers are increasingly seeking to use new strains, novel species, and next-generation probiotics, justification based on a significant history of use may be challenged. There are efforts underway by a variety of stakeholders, including the United States Pharmacopeia (USP), to develop best practices guidelines for assessing the quality and safety of probiotics. A current initiative of the USP seeks to provide expert advice specific to safety considerations for probiotics. Toward this goal, this review provides a helpful summary guide to global regulatory guidelines. We question the suitability of traditional animal toxicology studies designed for testing chemicals for relevance in assessing probiotic safety. This includes discussion of the use of excessive dose levels, the length of repeated dose toxicity studies needed, and the most suitable animal species used in toxicology studies. In addition, the importance of proper manufacturing practices with regard to final product safety are also included. Thus, an outline of essential parameters of a comprehensive safety assessment for a probiotic are provided.

In the original version of this Consensus Statement article published online, a bar in Figure 1 was incorrectly labelled as “parabiotics” when it should have been labelled as “paraprobiotics”. This error has now been corrected in the HTML and PDF version of the article. Figure 1 | Total number of mentions in the literature of different terms referring to inanimate microorganisms and/or their metabolites.

The value of exogenously supplied live bacteria for the maintenance of health in humans has been recognized both scientifically in the published literature and commercially in the availability of probiotic products. Although many bacteria characterized as probiotics are strains of Lactobacillus or Bifidobacterium, sporeforming bacteria, primarily of the genus Bacillus and related genera, have also been studied and commercialized as probiotics. This article reviews the characterization, efficacy, and safety of sporeformers used as probiotics.

In 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of experts specializing in nutrition, microbial physiology, gastroenterology, paediatrics, food science and microbiology to review the definition and scope of postbiotics. The term ‘postbiotics’ is increasingly found in the scientific literature and on commercial products, yet is inconsistently used and lacks a clear definition. The purpose of this panel was to consider the scientific, commercial and regulatory parameters encompassing this emerging term, propose a useful definition and thereby establish a foundation for future developments. The panel defined a postbiotic as a “preparation of inanimate microorganisms and/or their components that confers a health benefit on the host”. Effective postbiotics must contain inactivated microbial cells or cell components, with or without metabolites, that contribute to observed health benefits. The panel also discussed existing evidence of health-promoting effects of postbiotics, potential mechanisms of action, levels of evidence required to meet the stated definition, safety and implications for stakeholders. The panel determined that a definition of postbiotics is useful so that scientists, clinical triallists, industry, regulators and consumers have common ground for future activity in this area. A generally accepted definition will hopefully lead to regulatory clarity and promote innovation and the development of new postbiotic products.

In May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of nutritionists, physiologists and microbiologists to review the definition and scope of synbiotics. The panel updated the definition of a synbiotic to “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host”. The panel concluded that defining synbiotics as simply a mixture of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. Requiring that each component must meet the evidence and dose requirements for probiotics and prebiotics individually could also present an obstacle. Rather, the panel clarified that a complementary synbiotic, which has not been designed so that its component parts function cooperatively, must be composed of a probiotic plus a prebiotic, whereas a synergistic synbiotic does not need to be so. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the co-administered microorganisms. This Consensus Statement further explores the levels of evidence (existing and required), safety, effects upon targets and implications for stakeholders of the synbiotic concept., Gut microbiota can be manipulated to benefit host health, including the use of probiotics, prebiotics and synbiotics. This Consensus Statement outlines the definition and scope of the term ‘synbiotics’ as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in May 2019.

Still relevant after 19 years, the FAO/WHO definition of probiotics can be translated into four simple and pragmatic criteria allowing one to conclude if specific strains of microorganisms qualify as a probiotic for use in foods and dietary supplements. Probiotic strains must be (i) sufficiently characterized; (ii) safe for the intended use; (iii) supported by at least one positive human clinical trial conducted according to generally accepted scientific standards or as per recommendations and provisions of local/national authorities when applicable; and (iv) alive in the product at an efficacious dose throughout shelf life. We provide clarity and detail how each of these four criteria can be assessed. The wide adoption of these criteria is necessary to ensure the proper use of the word probiotic in scientific publications, on product labels, and in communications with regulators and the general public.

While probiotics have not been marketed as drugs, clinicians can still recommend them in an evidence-based manner.

Probiotic usage in food is widespread and growing. The objective of this study was to determine the percentage of probiotic food products sold in the refrigerated section of retail grocery stores in the Washington DC area that we could link to evidence of any health benefit. We surveyed refrigerated sections of eight large grocery stores representing five national chains for probiotic products. Based on declared probiotic composition (strain and count) for each product, we searched PubMed for controlled trials that provided evidence of any health benefit. Our assessment showed that 49% (22 out of 45 distinct probiotic foods) could be linked to evidence supporting a health benefit. All products indicating strain composition could be linked to evidence. Our study suggests that consumers have a reasonable likelihood of purchasing a refrigerated probiotic food with evidence, but room for improvement exists.

The administration of broad-spectrum antibiotics is often associated with antibiotic-associated diarrhea (AAD), and impacts gastrointestinal tract homeostasis, as evidenced by the following: (a) an overall reduction in both the numbers and diversity of the gut microbiota, and (b) decreased short-chain fatty acid (SCFA) production. Evidence in humans that probiotics may enhance the recovery of microbiota populations after antibiotic treatment is equivocal, and few studies have addressed if probiotics improve the recovery of microbial metabolic function. Our aim was to determine if Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-containing yogurt could protect against antibiotic-induced fecal SCFA and microbiota composition disruptions. We conducted a randomized, allocation-concealed, controlled trial of amoxicillin/clavulanate administration (days 1–7), in conjunction with either BB-12-containing or control yogurt (days 1–14). We measured the fecal levels of SCFAs and bacterial composition at baseline and days 7, 14, 21, and 30. Forty-two participants were randomly assigned to the BB-12 group, and 20 participants to the control group. Antibiotic treatment suppressed the fecal acetate levels in both the control and probiotic groups. Following the cessation of antibiotics, the fecal acetate levels in the probiotic group increased over the remainder of the study and returned to the baseline levels on day 30 (−1.6% baseline), whereas, in the control group, the acetate levels remained suppressed. Further, antibiotic treatment reduced the Shannon diversity of the gut microbiota, for all the study participants at day 7. The magnitude of this change was larger and more sustained in the control group compared to the probiotic group, which is consistent with the hypothesis that BB-12 enhanced microbiota recovery. There were no significant baseline clinical differences between the two groups. Concurrent administration of amoxicillin/clavulanate and BB-12 yogurt, to healthy subjects, was associated with a significantly smaller decrease in the fecal SCFA levels and a more stable taxonomic profile of the microbiota over time than the control group.

© 2019, Springer Nature Limited. Probiotics and prebiotics are microbiota-management tools for improving host health. They target gastrointestinal effects via the gut, although direct application to other sites such as the oral cavity, vaginal tract and skin is being explored. Here, we describe gut-derived effects in humans. In the past decade, research on the gut microbiome has rapidly accumulated and has been accompanied by increased interest in probiotics and prebiotics as a means to modulate the gut microbiota. Given the importance of these approaches for public health, it is timely to reiterate factual and supporting information on their clinical application and use. In this Review, we discuss scientific evidence on probiotics and prebiotics, including mechanistic insights into health effects. Strains of Lactobacillus, Bifidobacterium and Saccharomyces have a long history of safe and effective use as probiotics, but Roseburia spp., Akkermansia spp., Propionibacterium spp. and Faecalibacterium spp. show promise for the future. For prebiotics, glucans and fructans are well proven, and evidence is building on the prebiotic effects of other substances (for example, oligomers of mannose, glucose, xylose, pectin, starches, human milk and polyphenols).

Probiotics and prebiotics are microbiota-management tools for improving host health. They target gastrointestinal effects via the gut, although direct application to other sites such as the oral cavity, vaginal tract and skin is being explored. Here, we describe gut-derived effects in humans. In the past decade, research on the gut microbiome has rapidly accumulated and has been accompanied by increased interest in probiotics and prebiotics as a means to modulate the gut microbiota. Given the importance of these approaches for public health, it is timely to reiterate factual and supporting information on their clinical application and use. In this Review, we discuss scientific evidence on probiotics and prebiotics, including mechanistic insights into health effects. Strains of Lactobacillus, Bifidobacterium and Saccharomyces have a long history of safe and effective use as probiotics, but Roseburia spp., Akkermansia spp., Propionibacterium spp. and Faecalibacterium spp. show promise for the future. For prebiotics, glucans and fructans are well proven, and evidence is building on the prebiotic effects of other substances (for example, oligomers of mannose, glucose, xylose, pectin, starches, human milk and polyphenols).

Probiotic bacteria have long been believed to influence general health and well-being through their association with the gastrointestinal tract (GIT) and its normal microbiota. The microbiotas of humans, animals, and fowl vary considerably with the architecture of their GITs. Species of microorganisms are located at different locations throughout the GIT and include strains that are either harmful or beneficial to the host depending on the circumstances and specific strains involved. Probiotic microorganisms typically designed for delivery in dairy foods are most often members of the Lactobacillus or Bifidobacterium genus. This chapter discusses the effects of probiotics on GIT ecology, and deals with the appropriateness, technological suitability, competitiveness, and performance and functionality, as the criteria for selection of probiotic cultures. Prebiotics stimulate the growth and activity of beneficial bacteria in an individual’s intestinal microbiota. The best-known prebiotics are fructo-oligosaccharides derived from food sources. Production of designer prebiotics can offer multiple activities in retarding undesirable microorganisms, better promoting the native desirable microbiota, or stimulating the growth or activity of synbiotic cultures. Expansion of avenues for incorporation into appropriate food vehicles and improved stimulation of beneficial microfloras are some of the aspects that are good targets for development of prebiotics.

Acute respiratory tract infections (RTIs) of viral origin place a substantial burden on health care resources and society. Randomized controlled trials have shown positive effects of probiotics on clinical outcomes in these commonly occurring RTIs. Two meta-analyses published by the York Health Economics Consortium (YHEC) and Cochrane reported the efficacy of probiotics in reducing incidence and duration of RTIs, number of antibiotic courses, and days absent from work. The aim of this study was to assess the potential health-economic impact of probiotics on RTI-associated events and expenses in the US primary care setting. A state-transition microsimulation model reproduced a study population representative of the US national demographics for age and gender (1/1,000 sample). RTI incidence was based on the influenza-like illness outpatient consultation rate reported by the Centers for Disease Control and Prevention (CDC) FluView. Data on vaccination, on factors that negatively impact RTI outcomes, on resource utilization, and on productivity loss were obtained from US national databases. Analyses were performed for both meta-analyses independently. Outcomes included cost savings for the health care payer, related to a reduced number of RTI episodes, less outpatient consultations, and decreased medical prescriptions as well as cost savings from a broader societal perspective related to productivity loss. The analysis showed that generalized probiotic intake in the US population for 2017-2018 would have allowed cost savings for the health care payer of 4.6 million USD based on the YHEC scenario and 373 million USD for the Cochrane scenario, by averting 19 million and 54.5 million RTI sick days, respectively, compared to no probiotics. Antibiotic prescriptions decreased with 1.39-2.16 million courses, whereas absence from work decreased by 3.58-4.2 million days when applying the YHEC and Cochrane data, respectively. When productivity loss is included, total savings for society represented 784 million or 1.4 billion USD for the YHEC and Cochrane scenarios, respectively. Subgroup analyses demonstrated an incremental benefit of probiotics in at-risk groups, which might be of relevance for targeted interventions. Sensitivity analyses confirmed the robustness of the model outcomes. Our analysis demonstrated a positive impact of probiotics on the health care and economic burden of flu-like RTIs. Improved disease outcomes translated into considerable cost savings for both the payer and society.

This is a summary from a workshop convened as part of the 13th annual meeting of the International Scientific Association for Probiotics and Prebiotics. A group of 24 stakeholders, including clinical experts, researchers, federal government officials, funding agencies, lawyers and industry experts met to review the challenges of the current regulatory approach to human research on probiotics in the USA and to discuss ways to move research forward. There was agreement that some of the current regulatory requirements imposed on probiotic research in the United States hindered research progress and increased cost without improving study subject safety. Many situations were outlined by clinical investigators demonstrating the impact of regulatory delays on research progress. Additionally, research is compromised when study designs and outcomes require manipulation so as to invoke less burdensome regulatory requirements. These responses by investigators to regulatory requirements have placed United States' researchers at a disadvantage. The public ultimately suffer when research to clarify the role of these products on health is stalled. Workshop participants concurred that regulatory oversight should balance study subject vulnerability with documented safety for the intended use for the probiotic strain, and that human research on foods and supplements should not be be regulated as drug research. Challenges and potential improvement strategies are discussed.

The prebiotic concept was introduced twenty years ago, and despite several revisions to the original definition, the scientific community has continued to debate what it means to be a prebiotic. How prebiotics are defined is important not only for the scientific community, but also for regulatory agencies, the food industry, consumers and healthcare professionals. Recent developments in community-wide sequencing and glycomics have revealed that more complex interactions occur between putative prebiotic substrates and the gut microbiota than previously considered. A consensus among scientists on the most appropriate definition of a prebiotic is necessary to enable continued use of the term.

In a rapidly growing global probiotic market, end-users have difficulty distinguishing between high quality and poor quality products. This ambiguity threatens the trust consumers and healthcare providers have in probiotic products. To address this problem, we recommend that companies undergo third-party evaluations to certify probiotic quality and label accuracy. In order to communicate about product quality to end-users, indication of certification on product labels is helpful, although not all manufacturers choose to use this approach. Herein we discuss: third-party certification, the process of setting standards for identity, purity, and quantification of probiotics; some emerging methodologies useful for quality assessment; and some technical challenges unique to managing quality of live microbial products. This review provides insights of an Expert Panel engaged in this process and aims to update the reader on relevant current scientific methodologies. Establishing validated methodologies for all aspects of quality assessment is an essential component of this process and can be facilitated by established organizations, such as United States Pharmacopeia. Emerging methodologies including whole genome sequencing and flow cytometry are poised to play important roles in these processes.

[This corrects the article DOI: 10.3389/fphar.2019.00980.].

Background Overall reduction of antibiotic use is a widely adopted public health goal. Given evidence that consuming probiotics reduce the incidence, duration and/or severity of certain types of common acute infections, we hypothesized that probiotics are associated with reduced antibiotic use. This systematic review of randomized controlled trials (RCTs) assessed the impact of probiotic supplementation (any strain, dose or duration), compared to placebo, on antibiotic utilization for common, acute infections in otherwise healthy people of all ages. Methods We searched 13 electronic databases including MEDLINE, Embase and CENTRAL from inception to 17th January 2017. Backward and forward citation searches were also conducted. Two reviewers independently selected studies for inclusion and extracted study data. We assessed risk of bias for individual studies using criteria adapted from the Centre for Reviews and Dissemination, and the quality of evidence for each outcome was assessed using the GRADE system. Studies that evaluated similar outcomes were pooled statistically in meta-analyses using a random-effects model. Results We screened 1533 citations, and of these, 17 RCTs met our predefined inclusion criteria. All 17 were conducted in infants and/or children with a primary aim of preventing acute respiratory tract infections, acute lower digestive tract infections or acute otitis media. Included studies used 13 probiotic formulations, all comprising single or combination Lactobacillus and Bifidobacterium delivered in a range of food or supplement products. Mean duration of probiotic supplementation ranged from 4 days to 9 months. Trial quality was variable. Meta-analysis demonstrated that infants and children who received probiotics to prevent acute illnesses had a lower risk of being prescribed antibiotics, relative to those who received placebo (Pooled Relative Risk = 0.71, 95% CI: 0.54–0.94). When restricted to five studies with a low risk of bias, the pooled relative risk was 0.46 (95% CI: 0.23–0.97). Significant statistical heterogeneity was present in effect size estimates, which appeared to be due to one trial which could partly be considered as an outlier. Conclusions Probiotics, provided to reduce the risk for common acute infections, may be associated with reduced antibiotic use in infants and children. Additional well-designed studies are needed to substantiate these findings in children and explore similar findings in other population groups.

Strain-specificity of probiotic effects has been a cornerstone principle of probiotic science for decades. Certainly, some important mechanisms are present in only a few probiotic strains. But scientific advances now reveal commonalities among members of certain taxonomic groups of probiotic microbes. Some clinical benefits likely derive from these shared mechanisms, suggesting that sub-species-specific, species specific or genus-specific probiotic effects exist. Human trials are necessary to confirm specific health benefits. However, a strain that has not been tested in human efficacy trials may meet the minimum definition of the term `probiotic' if it is a member of a well-studied probiotic species expressing underlying core mechanisms and it is delivered at an effective dose.

With the continued interest in the role of the gut microbiota in health, attention has now turned to how to harness the microbiota for the benefit of the host. This Consensus Statement outlines the definition and scope of the term 'prebiotic' as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in December 2016. In December 2016, a panel of experts in microbiology, nutrition and clinical research was convened by the International Scientific Association for Probiotics and Prebiotics to review the definition and scope of prebiotics. Consistent with the original embodiment of prebiotics, but aware of the latest scientific and clinical developments, the panel updated the definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit. This definition expands the concept of prebiotics to possibly include non-carbohydrate substances, applications to body sites other than the gastrointestinal tract, and diverse categories other than food. The requirement for selective microbiota-mediated mechanisms was retained. Beneficial health effects must be documented for a substance to be considered a prebiotic. The consensus definition applies also to prebiotics for use by animals, in which microbiota-focused strategies to maintain health and prevent disease is as relevant as for humans. Ultimately, the goal of this Consensus Statement is to engender appropriate use of the term 'prebiotic' by relevant stakeholders so that consistency and clarity can be achieved in research reports, product marketing and regulatory oversight of the category. To this end, we have reviewed several aspects of prebiotic science including its development, health benefits and legislation.

OBJECTIVES Probiotics are live microorganisms that may provide health benefits to the individual when consumed in sufficient quantities. For studies conducted on health or disease endpoints on probiotics in the United States, the Food and Administration has required those studies to be conducted as investigational new drugs. This phase I, double-blinded, randomized, controlled safety study represents the first requirement of this pathway. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp. lactis (B lactis) strain BB-12 (BB-12)-supplemented yogurt when consumed by a generally healthy group of children. The secondary aim was to assess the effect of BB-12-supplemented yogurt on the gut microbiota of the children. METHODS Sixty children ages 1 to 5 years were randomly assigned to consume 4 ounces of either BB-12-supplemented yogurt or nonsupplemented control yogurt daily for 10 days. The primary outcome was to assess safety and tolerability, as determined by the number of reported adverse events. RESULTS A total of 186 nonserious adverse events were reported, with no significant differences between the control and BB-12 groups. No significant changes due to probiotic treatment were observed in the gut microbiota of the study cohort. CONCLUSIONS BB-12-supplemented yogurt is safe and well-tolerated when consumed by healthy children. The present study will form the basis for future randomized clinical trials investigating the potential effects of BB-12-supplemented yogurt in different disease states.

An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic--"live microorganisms which when administered in adequate amounts confer a health benefit on the host"--was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.

Recent systematic reviews have reported a positive, although modest, effect of probiotics in terms of preventing common cold symptoms. In this systematic review, the effect of probiotics, specifically Lactobacillus and Bifidobacterium strains, on the duration of acute respiratory infections in otherwise healthy children and adults was evaluated. To identify relevant trials, eight databases, including MEDLINE, Embase, the Cochrane Database of Systematic Reviews (CDSR), the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), Science Citation Index (SCI) and OAISTER, were searched from inception to 20 July 2012. Details regarding unpublished studies/databases were also obtained from probiotic manufacturers. Study selection, data extraction and quality assessment were carried out by two reviewers. Risk of bias was assessed using criteria adapted from those published by the Centre for Reviews and Dissemination. In this review, twenty randomised controlled trials (RCT) were included, of which twelve were considered to have a low risk of bias. Meta-analysis revealed significantly fewer numbers of days of illness per person (standardised mean difference (SMD) − 0·31 (95 % CI − 0·41, − 0·11), I2= 3 %), shorter illness episodes by almost a day (weighted mean difference − 0·77 (95 % CI − 1·50, − 0·04), I2= 80 %) (without an increase in the number of illness episodes), and fewer numbers of days absent from day care/school/work (SMD − 0·17 (95 % CI − 0·31, − 0·03), I2= 67 %) in participants who received a probiotic intervention than in those who had taken a placebo. Reasons for heterogeneity between the studies were explored in subgroup analysis, but could not be explained, suggesting that the effect sizes found may differ between the population groups. This systematic review provides evidence from a number of good-quality RCT that probiotics reduce the duration of illness in otherwise healthy children and adults.

Commercial probiotic strains for food or supplement use can be altered in different ways for a variety of purposes. Production conditions for the strain or final product may be changed to address probiotic yield, functionality, or stability. Final food products may be modified to improve flavor and other sensory properties, provide new product formats, or respond to market opportunities. Such changes can alter the expression of physiological traits owing to the live nature of probiotics. In addition, genetic approaches may be used to improve strain attributes. This review explores whether genetic or phenotypic changes, by accident or design, might affect the efficacy or safety of commercial probiotics. We highlight key issues important to determining the need to re-confirm efficacy or safety after strain improvement, process optimization, or product formulation changes. Research pinpointing the mechanisms of action for probiotic function and the development of assays to measure them are greatly needed to better understand if such changes have a substantive impact on probiotic efficacy.

Probiotics and prebiotics are useful interventions for improving human health through direct or indirect effects on the colonizing microbiota. However, translation of these research findings into nutritional recommendations and public health policy endorsements has not been achieved in a manner consistent with the strength of the evidence. More progress has been made with clinical recommendations. Conclusions include that beneficial cultures, including probiotics and live cultures in fermented foods, can contribute towards the health of the general population; prebiotics, in part due to their function as a special type of soluble fiber, can contribute to the health of the general population; and a number of challenges must be addressed in order to fully realize probiotic and prebiotic benefits, including the need for greater awareness of the accumulated evidence on probiotics and prebiotics among policy makers, strategies to cope with regulatory roadblocks to research, and high-quality human trials that address outstanding research questions in the field.

The effects of probiotic supplementation on fecal microbiota composition in healthy adults have not been well established. We aimed to provide a systematic review of the potential evidence for an effect of probiotic supplementation on the composition of human fecal microbiota as assessed by high-throughput molecular approaches in randomized controlled trials (RCTs) of healthy adults.The survey of peer-reviewed papers was performed on 17 August 2015 by a literature search through PubMed, SCOPUS, and ISI Web of Science. Additional papers were identified by checking references of relevant papers. Search terms included healthy adult, probiotic, bifidobacterium, lactobacillus, gut microbiota, fecal microbiota, intestinal microbiota, intervention, and (clinical) trial. RCTs of solely probiotic supplementation and placebo in healthy adults that examined alteration in composition of overall fecal microbiota structure assessed by shotgun metagenomic sequencing, 16S ribosomal RNA sequencing, or phylogenetic microarray methods were included. Independent collection and quality assessment of studies were performed by two authors using predefined criteria including methodological quality assessment of reports of the clinical trials based on revised tools from PRISMA/Cochrane and by the Jadad score.Seven RCTs investigating the effect of probiotic supplementation on fecal microbiota in healthy adults were identified and included in the present systematic review. The quality of the studies was assessed as medium to high. Still, no effects were observed on the fecal microbiota composition in terms of α-diversity, richness, or evenness in any of the included studies when compared to placebo. Only one study found that probiotic supplementation significantly modified the overall structure of the fecal bacterial community in terms of β-diversity when compared to placebo.This systematic review of the pertinent literature demonstrates a lack of evidence for an impact of probiotics on fecal microbiota composition in healthy adults. Future studies would benefit from pre-specifying the primary outcome and transparently reporting the results including effect sizes, confidence intervals, and P values as well as providing a clear distinction of between-group and within-group comparisons.

The scientific literature has demonstrated that probiotics have a broad spectrum of activity, although often the results are contradictory. This study provides a critical overview of the current meta-analyses that have evaluated the efficacy of probiotics in physiologic and pathological conditions, such as metabolic disease, antibiotic-associated and Clostridium difficile-associated diarrhea, IBS, constipation, IBD, chemotherapy-associated diarrhea, respiratory tract infection, ventilator-associated pneumonia, NAFLD, liver encephalopathy, periodontitis, depression, vaginosis, urinary tract infections, pancreatitis, incidence of ventilator-associated pneumonia, hospital infection and stay in ICU, mortality of post-trauma patients, necrotising enterocolitis in premature infants. Only for antibiotic- and Clostridium difficile-associated diarrhea, and respiratory tract infections the effects of probiotics are considered "evidence-based." Concerning other fields, meta-analyses lacks to define type and biologic effect of probiotic strains, as well as the outcome in a disease state. Therefore, the results presented should be a stimulus for further studies which will provide clinical recommendations.

Although precise mechanisms responsible for all demonstrations of probiotic health benefits are not known, many lines of evidence suggest that probiotics function through direct or indirect impact on colonizing microbiota of the gut. Probiotics can directly influence colonizing microbes through multiple mechanisms, including the production of inhibitory compounds (bacteriocins, short chain fatty acids, and others), by producing substrates that might promote the growth of colonizing microbes (secreted exopolysaccharides, vitamins, fatty acids, sugars from undigested carbohydrates and others), and by promoting immune responses against specific microbes. Indirectly, probiotics can influence colonizing microbes by inhibiting attachment through stimulated mucin production, reinforcing gut barrier effects, and downregulation of gut inflammation, thereby promoting microbes that are associated with a healthier gut physiology. Although the value of targeted changes in populations of gut bacteria is a matter of debate, increased levels of Bifidobacterium and Lactobacillus in the gut correlate with numerous health endpoints. Microbiota changes due to probiotic intake include increased numbers of related phylotypes, decreasing pathogens and their toxins, altering bacterial community structure to enhance evenness, stabilizing bacterial communities when perturbed (eg, with antibiotics), or promoting a more rapid recovery from a perturbation. Further research will provide insight into the degree of permanence of probiotic-induced changes, although research to date suggests that continued probiotic consumption is needed for sustained impact.