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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.

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.

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.

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).

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.

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 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.

Presented by the New York Academy of Sciences, the U.S. Food and Drug Administration (FDA), and the U.S. Office of Dietary Supplements of the National Institutes of Health, the symposium “Probiotic Foods and Supplements: The Science and Regulations of Labeling,” was held on June 12, 2010 at the New York Academy of Sciences, New York, NY, the goals of which were to facilitate the exchange of ideas regarding labeling and substantiation of claims for probiotics among academic, industry, and regulatory professionals, and to discuss ways to translate and communicate research results in a truthful way to the consumer and to such health professionals as physicians, pharmacists, and dieticians. The target audience for this symposium included academicians interested in conducting research on the health benefits of probiotics; scientists; communications personnel, and regulatory specialists from companies involved in, or interested in, the marketing of probiotics; U.S. government regulatory experts tasked with oversight of probiotic foods and dietary supplement products; and other experts in the field interested in the development of probiotics for the U.S. market.

Fecal microbiota transplantation (FMT) has emerged as an effective treatment for C. difficile infection (CDI) refractory to antibiotic therapy alone. Given the important roles of microbiota in the function of the gastrointestinal tract and other aspects of human physiology, there is also growing interest in studying FMT for other clinical indications. The U.S. Food and Drug Administration has determined that FMT constitutes a drug and is an investigational agent; as such an investigational new drug application (IND) is encouraged in treatment of recurrent CDI and required to administer FMT for any other indications. Most physicians and investigators do not have the regulatory experience necessary to navigate the IND process easily. Our aim is to provide guidance to others who are interested in obtaining an IND to perform or study FMT.

“Probiotics: From Bench to Market” was a one-day conference convened by the New York Academy of Sciences on June 11, 2010, with the goal of stimulating discussion of the physiological effects of probiotics on the gastrointestinal, nervous, and immune systems. The program included speakers from academia, industry, and government to give conference participants a full understanding of the state of the field of probiotics. The overall goal of the program was to increase communication and collaboration among these groups to advance probiotic research and probiotic contributions to public health. The conference was divided into three sessions and included both oral and visual presentations as well as panel discussions.

Background: To evaluate whether a fermented dairy drink containing the probiotic strain Lactobacillus casei DN-114 001 could reduce the incidence of common infectious diseases (CIDs) and the change of behavior because of illness in children. Subjects/Methods: We conducted a double-blinded, randomized, placebo-controlled allocation concealment clinical trial in the Washington, DC metropolitan area. Participants were 638 children 3–6 years old in daycare/schools. The intervention was a fermented dairy drink containing a specific probiotic strain or matching placebo with no live cultures for 90 consecutive days. Two primary outcomes were assessed: incidence of CIDs and change of behavior because of illness (both assessed by parental report). Results: The rate of change of behavior because of illness was similar among active and control groups. However, the incidence rate for CIDs in the active group (0.0782) is 19% lower than that of the control group (0.0986) (incidence rate ratio=0.81, 95% CI: 0.65, 099) P=0.046. Conclusions: Daily intake of a fermented dairy drink containing the probiotic strain L. casei DN-114 001 showed some promise in reducing overall incidence of illness, but was primarily driven by gastrointestinal infections and there were no differences in change of behavior.

uses of probiotics along with current knowledge of probiotic organisms, their properties, and their mechanisms of action. The program included scientific presentations about advances in understanding of the relationship between the gastrointestinal microbiota and the development of the innate and adaptive immune system, as well as the implications of this relationship for current uses of and research on probiotics (table 1). Unlike other workshops held to date, the program examined the critically important interface between science and regulation. Speakers addressed the impact that science has on the way in which products are regulated and the equally important impact that regulations have on how research is planned and conducted, how product information is conveyed to consumers and health care professionals, and how products are ultimately marketed. The articles and discussions in this supplement address these topics that were presented in each panel. This article summarizes the findings of the conference and the recommendations made for future directions relating to research on probiotics.

Interest in probiotics is at an all-time high in the United States, driven in part by new products emerging in the market, by US researchers eager to evaluate efficacy claims rigorously, and by consumers interested in potential therapeutic and preventive health benefits. The US marketplace is a mixed bag of products, some well-defined and properly evaluated in controlled clinical studies and others with unsubstantiated claims of efficacy. Validation of probiotic contents in commercial products is needed to ensure consumer confidence. The term "probiotic" should be used only for products that meet the scientific criteria for this term-namely, products that contain an adequate dose of live microbes that have been documented in target-host studies to confer a health benefit. Probiotics must be identified to the level of strain, must be characterized for the specific health target, and must be formulated into products using strains and doses shown to be efficacious. Several characteristics commonly presumed to be essential to probiotics, such as human origin and the ability to improve the balance of the intestinal microbiota, are discussed.

The field of probiotics continues to evolve and progress. This paper reviews several situations within the probiotic field that are of current interest, including review of the scope of the proper use of the term "probiotic," use of systematic reviews and meta-analyses for probiotics, regulatory challenges to doing human research on probiotics in the United States, medical recommendations for probiotic use, and safety assurance for probiotics used for vulnerable populations. The greatest need in the probiotic field remains well-conducted and well-reported human trials, to better define the functionality of probiotics for different indications and populations.

The role that functional foods might play in enhancing human health is continuing to develop. Comprehensive approaches, which will enable scientists both to understand the total human physiological response to diet (through application of human genomics and metabolomics) and evaluate health maintenance rather than disease incidence, will advance this field greatly. In the United States, functional foods remain of interest to consumers, although there is currently no legal definition of a functional food. One functional ingredient, probiotics, shows much promise as a health-promoting addition to foods, or as a basis for dietary supplements. A growth industry in the United States, the probiotics industry must develop a proactive policy in order to bolster consumer confidence in commercial probiotic products. Many publications suggest that commercial probiotic products do not comply with label claims. This article seeks to examine probiotics as functional food ingredients and the regulatory framework for labelling and describing the benefits of functional foods, as well as dietary supplements.

Probiotics are live microorganisms that, when administered in sufficient doses, provide health benefits on the host. The United States Food and Drug Administration (FDA) requires phase I safety studies for probiotics when the intended use of the product is as a drug. 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 adults who were prescribed a 10-day course of antibiotics for a respiratory infection. Secondary aims were to assess the ability of BB-12 to affect the expression of whole blood immune markers associated with cell activation and inflammatory response. A phase I, double-blinded, randomized controlled study was conducted in compliance with FDA guidelines for an Investigational New Drug (IND). Forty participants were randomly assigned to consume 4 ounces of either BB-12 -supplemented yogurt or non-supplemented control yogurt daily for 10 d. The primary outcome was to assess safety and tolerability, assessed by the number of reported adverse events. A total of 165 non-serious adverse events were reported, with no differences between the control and BB-12 groups. When compared to the control group, B lactis fecal levels were modestly higher in the BB-12-supplemented group. In a small subset of patients, changes in whole blood expression of genes associated with regulation and activation of immune cells were detected in the BB-12-supplemented group. BB-12-supplemented yogurt is safe and well tolerated when consumed by healthy adults concurrently taking antibiotics. This study will form the basis for future randomized clinical trials investigating the potential immunomodulatory effects of BB-12-supplemented yogurt in a variety of disease states.

This paper describes the consensus opinion of the participants in the 4th Triennial Yale/Harvard Workshop on Probiotic Recommendations. The recommendations update those of the first 3 meetings that were published in 2006, 2008, and 2011. Recommendations for the use of probiotics in necrotizing enterocolitis, childhood diarrhea, inflammatory bowel disease, irritable bowel syndrome and Clostridium difficile diarrhea are reviewed. In addition, we have added recommendations for liver disease for the first time. As in previous publications, the recommendations are given as A, B, or C ratings.

Oral consumption of probiotic bacteria has the potential to support the health of American consumers. This paper will discuss the rationale of the probiotic theory, several health targets for probiotic bacteria, probiotic products in the U.S. and, finally, issues pertaining to communication about probiotic products to the consumer.

Curiosity about probiotic bacteria is high. This is not surprising given the rapid growth of the natural products market in the USA, which was 22% in 1995 (New Hope Natural Media, Boulder, CO). Although probiotic cultures are only one component of that market, this trend shows that consumers in the USA are increasingly taking a pro-active stance towards their health and are purchasing products not only to eliminate what is perceived as dietary negatives but to increase the levels of dietary positives (Wrick, 1995). This shift in consumer attitude bodes well for the development of the American probiotic market. This article describes the composition, promotion and labelling of probiotic-containing products, discusses attributes of commercial probiotic bacteria, and estimates the size of the probiotic market in the USA. This market information was obtained from several published (Anon, 1996a,b)and unpublished but commercially available (SPINS Information Services, San Francisco, CA and New Hope Natural Media, Boulder, CO) sources.

Foods which promote health beyond providing basic nutrition are termed ‘functional foods’. These foods have potential to promote health in ways not anticipated by traditional nutrition science. The international marketplace is the development ground for these products, even though scientific or regulatory consensus on their definition or significance has not been advanced. This article defines, provides examples of, discusses the consumer interest in, and considers the difficulty of developing scientific substantiation for effectiveness of functional foods. Probiotic bacteria are specifically used as an example in scientific approaches toward determining efficacy.

Recent advances in our understanding of the community structure and function of the human microbiome have implications for the potential role of probiotics and prebiotics in promoting human health. A group of experts recently met to review the latest advances in microbiota/microbiome research and discuss the implications for development of probiotics and prebiotics, primarily as they relate to effects mediated via the intestine. The goals of the meeting were to share recent advances in research on the microbiota, microbiome, probiotics, and prebiotics, and to discuss these findings in the contexts of regulatory barriers, evolving healthcare environments, and potential effects on a variety of health topics, including the development of obesity and diabetes; the long-term consequences of exposure to antibiotics early in life to the gastrointestinal (GI) microbiota; lactose intolerance; and the relationship between the GI microbiota and the central nervous system, with implications for depression, cognition, satiety, and mental health for people living in developed and developing countries. This report provides an overview of these discussions.

Probiotic bacteria are increasingly incorporated into food products intended to confer health benefits in the human gut and beyond. Little is known about how the food matrix and product formulation impacts probiotic functionality, even though such information is essential to scientific understanding and regulatory substantiation of health benefits. The food format has the potential to affect probiotic survival, physiology, and potentially efficacy, but few comparative studies in humans have been conducted. Human studies should account for the effects of the food base on human health and the bioactive components present in the foods that may augment or diminish interactions of the probiotic with the human host. Some studies show that food ingredients such as prebiotics and milk components can improve probiotic survival during the shelf life of foods, which may enhance probiotic efficacy through increased dose effects. Furthermore, there are indications that synbiotic products are more effective than either probiotics or prebiotics alone. Identification of probiotic adaptations to the food and gut environments holds promise for determining the specific cell components and potential bacterial-food interactions necessary for health benefits and determining how these factors are affected by changes in food formulation and host diet. These studies, combined with controlled human studies, are important future research activities for advancing this field.

This study describes the consensus opinion of the participants of the third Yale Workshop on probiotic use. There were 10 experts participating. The recommendations update those of the first 2 meetings that were published in 2005 and 2008. The workshop presentations and papers in this supplement relate to the involvement of normal microbiota involved in intestinal microecology, how the microbes interact with the intestine to affect our immunologic responses, the stability and natural history of probiotic organisms, and the role of the intestinal microbatome with regard to affecting cardiac risk factors and obesity. Recommendations for the use of probiotics in necrotizing enterocolitis, childhood diarrhea, inflammatory bowel disease, irritable bowel syndrome, and Clostridium difficile diarrhea are reviewed. As in previous publications, the recommendations are given as A, B, or C ratings. The recent positive experiences with bacteriotherapy (fecal microbiome transplant) are also discussed in detail and a positive recommendation is made for use in severe resistant C. difficile diarrhea.

To determine if consumption of yogurt containing a high dose of probiotic (1 × 1010 colony-forming unit per 100 ml), Bifidobacterium animalis subsp. lactis (B. lactis), decreases absences in children 2–4 years attending daycare/school centers. We conducted a double-blinded, randomized, placebo-controlled, allocation concealment clinical trial in the Washington, DC area. Our active intervention was a strawberry yogurt-based drink supplemented with B. lactis BB-12. The placebo was indistinguishable from the active drink, differing only in absence of the probiotic BB-12. A total of 172 children between the ages of 2 and 4 from the Washington, DC area were enrolled. The primary outcome, missed days of school because of illness per 100 days, was similar in both the active (2.54 days absent/100 school days) and control groups (2.42 days absent/100 school days) (P=0.873). The probiotic-containing yogurt-based beverage studied did not decrease absences because of illnesses in daycare/school for healthy children ages 2–4 years.

Probiotic functional foods are widely advertised to consumers primarily based on probiotic supplements. Determine if consumption of yogurt containing a high dose of probiotics improves health in children ages 1–3 years attending daycare/school centers. Double-blinded, randomized, placebo-controlled, allocation concealment clinical trial. Setting: Outpatient participants in the Washington, DC area. Participants: 182 healthy children between the age of 1 and 3 years attending daycare/school at least 3 days a week. Intervention: Active was a strawberry yogurt-based drink supplemented with Bifidobacterium animalis ssp. lactis (B. lactis) BB-12. The placebo was indistinguishable from the active drink, differing only in absence of the probiotic BB-12. Primary objective was to determine if consumption of a probiotic-containing yogurt-based drink decreases absences due to illnesses from daycare for children ages 1–3 years. Secondary was to determine if probiotic-containing yogurt-based drink improves overall parental satisfaction due to decreased absences from work and an overall healthier child. There were no significant differences in the days of missed school per group, with 51.9% in the active group and 47.1% in the placebo group missing at least 1 day of school throughout the study. Additionally, there were no differences in any secondary outcomes among the groups. Consumption of a yogurt-based drink delivering 1010 CFU of Bifidobacterium animalis ssp. lactis (B. lactis) BB-12 per day did not decrease the number of days missed of school due to an illness. Additional independent research on the potential of BB-12 to reduce illness in children needs to be conducted.