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    Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Ford Alexander C,Quigley Eamonn M M,Lacy Brian E,Lembo Anthony J,Saito Yuri A,Schiller Lawrence R,Soffer Edy E,Spiegel Brennan M R,Moayyedi Paul The American journal of gastroenterology OBJECTIVES:Irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC) are functional bowel disorders. Evidence suggests that disturbance in the gastrointestinal microbiota may be implicated in both conditions. We performed a systematic review and meta-analysis to examine the efficacy of prebiotics, probiotics, and synbiotics in IBS and CIC. METHODS:MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to December 2013). Randomized controlled trials (RCTs) recruiting adults with IBS or CIC, which compared prebiotics, probiotics, or synbiotics with placebo or no therapy, were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardized or weighted mean difference with a 95% CI. RESULTS:The search strategy identified 3,216 citations. Forty-three RCTs were eligible for inclusion. The RR of IBS symptoms persisting with probiotics vs. placebo was 0.79 (95% CI 0.70-0.89). Probiotics had beneficial effects on global IBS, abdominal pain, bloating, and flatulence scores. Data for prebiotics and synbiotics in IBS were sparse. Probiotics appeared to have beneficial effects in CIC (mean increase in number of stools per week=1.49; 95% CI=1.02-1.96), but there were only two RCTs. Synbiotics also appeared beneficial (RR of failure to respond to therapy=0.78; 95% CI 0.67-0.92). Again, trials for prebiotics were few in number, and no definite conclusions could be drawn. CONCLUSIONS:Probiotics are effective treatments for IBS, although which individual species and strains are the most beneficial remains unclear. Further evidence is required before the role of prebiotics or synbiotics in IBS is known. The efficacy of all three therapies in CIC is also uncertain. 10.1038/ajg.2014.202
    Recent developments in prebiotics to selectively impact beneficial microbes and promote intestinal health. Rastall Robert A,Gibson Glenn R Current opinion in biotechnology Prebiotics are non-digestible food ingredients that have a specific stimulatory effect upon selected populations of gut bacteria. The usual target microorganisms for prebiotic approaches are bifidobacteria. Numerous human feeding studies have shown the prebiotic influences that galactans and fructans can exert. Other candidate prebiotics are under investigation. The field is now moving towards identifying the health aspect associated with their use. Many avenues of gut related health are being researched, including reduction of diarrhoea, immune stimulation, and improved mineral bioavailability. Most current emphasis appears to be towards various parameters associated with metabolic syndrome. These include markers of insulin resistance, appetite, satiety, blood lipids and inflammatory status. 10.1016/j.copbio.2014.11.002
    Novel probiotics and prebiotics: road to the market. Kumar Himanshu,Salminen Seppo,Verhagen Hans,Rowland Ian,Heimbach Jim,Bañares Silvia,Young Tony,Nomoto Koji,Lalonde Mélanie Current opinion in biotechnology Novel probiotics and prebiotics designed to manipulate the gut microbiota for improving health outcomes are in demand as the importance of the gut microbiota in human health is revealed. The regulations governing introduction of novel probiotics and prebiotics vary by geographical region. Novel foods and foods with health claims fall under specific regulations in several countries. The paper reviews the main requirements of the regulations in the EU, USA, Canada and Japan. We propose a number of areas that need to be addressed in any safety assessment of novel probiotics and prebiotics. These include publication of the genomic sequence, antibiotic resistance profiling, selection of appropriate in vivo model, toxicological studies (including toxin production) and definition of target population. 10.1016/j.copbio.2014.11.021
    Prebiotics and Probiotics in Digestive Health. Quigley Eamonn M M Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association As the importance of the gut microbiota in health and disease is increasingly recognized interest in interventions that can modulate the microbiota and its interactions with its host has soared. Apart from diet, prebiotics and probiotics represent the most commonly used substances taken in an effort to sustain a healthy microbiome or restore balance when it is believed bacterial homeostasis has been disturbed in disease. While a considerable volume of basic science attests to the ability of various prebiotic molecules and probiotic strains to beneficially influence host immune responses, metabolic processes and neuro-endocrine pathways, the evidence base from human studies leaves much to be desired. This translational gap owes much to the manner in which this sector is regulated but also speaks to the challenges that confront the investigator who seeks to explore microbiota modulation in either healthy populations or those who suffer from common digestive ailments. For many products marketed as probiotics, some of the most fundamental issues relating to quality control, such as characterization, formulation, viability safety are scarcely addressed. 10.1016/j.cgh.2018.09.028
    New approaches for bacteriotherapy: prebiotics, new-generation probiotics, and synbiotics. Patel Rachna,DuPont Herbert L Clinical infectious diseases : an official publication of the Infectious Diseases Society of America The gut microbiota has a significant role in human health and disease. Dysbiosis of the intestinal ecosystem contributes to the development of certain illnesses that can be reversed by favorable alterations by probiotics. The published literature was reviewed to identify scientific data showing a relationship between imbalance of gut bacteria and development of diseases that can be improved by biologic products. The medical conditions vary from infectious and antibiotic-associated diarrhea to obesity to chronic neurologic disorders. A number of controlled clinical trials have been performed to show important biologic effects in a number of these conditions through administration of prebiotics, probiotics, and synbiotics. Controlled clinical trials have identified a limited number of prebiotics, probiotic strains, and synbiotics that favorably prevent or improve the symptoms of various disorders including inflammatory bowel disease, irritable bowel syndrome, infectious and antibiotic-associated diarrhea, diabetes, nonalcoholic fatty liver disease, necrotizing enterocolitis in very low birth weight infants, and hepatic encephalopathy. Studies have shown that probiotics alter gut flora and lead to elaboration of flora metabolites that influence health through 1 of 3 general mechanisms: direct antimicrobial effects, enhancement of mucosal barrier integrity, and immune modulation. Restoring the balance of intestinal flora by introducing probiotics for disease prevention and treatment could be beneficial to human health. It is also clear that significant differences exist between different probiotic species. Metagenomics and metatranscriptomics together with bioinformatics have allowed us to study the cross-talk between the gut microbiota and the host, furthering insight into the next generation of biologic products. 10.1093/cid/civ177
    A Critical Look at Prebiotics Within the Dietary Fiber Concept. Verspreet Joran,Damen Bram,Broekaert Willem F,Verbeke Kristin,Delcour Jan A,Courtin Christophe M Annual review of food science and technology This article reviews the current knowledge of the health effects of dietary fiber and prebiotics and establishes the position of prebiotics within the broader context of dietary fiber. Although the positive health effects of specific fibers on defecation, reduction of postprandial glycemic response, and maintenance of normal blood cholesterol levels are generally accepted, other presumed health benefits of dietary fibers are still debated. There is evidence that specific dietary fibers improve the integrity of the epithelial layer of the intestines, increase the resistance against pathogenic colonization, reduce the risk of developing colorectal cancer, increase mineral absorption, and have a positive impact on the immune system, but these effects are neither generally acknowledged nor completely understood. Many of the latter effects are thought to be particularly elicited by prebiotics. Although the prebiotic concept evolved significantly during the past two decades, the line between prebiotics and nonprebiotic dietary fiber remains vague. Nevertheless, scientific evidence demonstrating the health-promoting potential of prebiotics continues to accumulate and suggests that prebiotic fibers have their rightful place in a healthy diet. 10.1146/annurev-food-081315-032749
    Prebiotics: why definitions matter. Hutkins Robert W,Krumbeck Janina A,Bindels Laure B,Cani Patrice D,Fahey George,Goh Yong Jun,Hamaker Bruce,Martens Eric C,Mills David A,Rastal Robert A,Vaughan Elaine,Sanders Mary Ellen Current opinion in biotechnology 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. 10.1016/j.copbio.2015.09.001
    Dietary fiber and prebiotics and the gastrointestinal microbiota. Holscher Hannah D Gut microbes The gastrointestinal microbiota has an important role in human health, and there is increasing interest in utilizing dietary approaches to modulate the composition and metabolic function of the microbial communities that colonize the gastrointestinal tract to improve health, and prevent or treat disease. One dietary strategy for modulating the microbiota is consumption of dietary fiber and prebiotics that can be metabolized by microbes in the gastrointestinal tract. Human alimentary enzymes are not able to digest most complex carbohydrates and plant polysaccharides. Instead, these polysaccharides are metabolized by microbes which generate short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate. This article reviews the current knowledge of the impact of fiber and prebiotic consumption on the composition and metabolic function of the human gastrointestinal microbiota, including the effects of physiochemical properties of complex carbohydrates, adequate intake and treatment dosages, and the phenotypic responses related to the composition of the human microbiota. 10.1080/19490976.2017.1290756
    Can prebiotics and probiotics improve therapeutic outcomes for undernourished individuals? Sheridan Paul O,Bindels Laure B,Saulnier Delphine M,Reid Gregor,Nova Esther,Holmgren Kerstin,O'Toole Paul W,Bunn James,Delzenne Nathalie,Scott Karen P Gut microbes It has become clear in recent years that the human intestinal microbiota plays an important role in maintaining health and thus is an attractive target for clinical interventions. Scientists and clinicians have become increasingly interested in assessing the ability of probiotics and prebiotics to enhance the nutritional status of malnourished children, pregnant women, the elderly, and individuals with non-communicable disease-associated malnutrition. A workshop was held by the International Scientific Association for Probiotics and Prebiotics (ISAPP), drawing on the knowledge of experts from industry, medicine, and academia, with the objective to assess the status of our understanding of the link between the microbiome and under-nutrition, specifically in relation to probiotic and prebiotic treatments for under-nourished individuals. These discussions led to four recommendations:   (1) The categories of malnourished individuals need to be differentiated To improve treatment outcomes, subjects should first be categorized based on the cause of malnutrition, additional health-concerns, differences in the gut microbiota, and sociological considerations. (2) Define a baseline "healthy" gut microbiota for each category Altered nutrient requirement (for example, in pregnancy and old age) and individual variation may change what constitutes a healthy gut microbiota for the individual. (3) Perform studies using model systems to test the effectiveness of potential probiotics and prebiotics against these specific categories These should illustrate how certain microbiota profiles can be altered, as members of different categories may respond differently to the same treatment. (4) Perform robust well-designed human studies with probiotics and/or prebiotics, with appropriate, defined primary outcomes and sample size These are critical to show efficacy and understand responder and non-responder outcomes. It is hoped that these recommendations will lead to new approaches that combat malnutrition. This report is the result of discussion during an expert workshop titled "How do the microbiota and probiotics and/or prebiotics influence poor nutritional status?" held during the 10th Meeting of the International Scientific Association for Probiotics and Prebiotics (ISAPP) in Cork, Ireland from October 1-3, 2012. The complete list of workshop attendees is shown in Table 1. 10.4161/gmic.27252
    From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Koh Ara,De Vadder Filipe,Kovatcheva-Datchary Petia,Bäckhed Fredrik Cell A compelling set of links between the composition of the gut microbiota, the host diet, and host physiology has emerged. Do these links reflect cause-and-effect relationships, and what might be their mechanistic basis? A growing body of work implicates microbially produced metabolites as crucial executors of diet-based microbial influence on the host. Here, we will review data supporting the diverse functional roles carried out by a major class of bacterial metabolites, the short-chain fatty acids (SCFAs). SCFAs can directly activate G-coupled-receptors, inhibit histone deacetylases, and serve as energy substrates. They thus affect various physiological processes and may contribute to health and disease. 10.1016/j.cell.2016.05.041
    The Impact of Dietary Fiber on Gut Microbiota in Host Health and Disease. Makki Kassem,Deehan Edward C,Walter Jens,Bäckhed Fredrik Cell host & microbe Food is a primordial need for our survival and well-being. However, diet is not only essential to maintain human growth, reproduction, and health, but it also modulates and supports the symbiotic microbial communities that colonize the digestive tract-the gut microbiota. Type, quality, and origin of our food shape our gut microbes and affect their composition and function, impacting host-microbe interactions. In this review, we will focus on dietary fibers, which interact directly with gut microbes and lead to the production of key metabolites such as short-chain fatty acids, and discuss how dietary fiber impacts gut microbial ecology, host physiology, and health. Hippocrates' notion "Let food be thy medicine and medicine be thy food" remains highly relevant millennia later, but requires consideration of how diet can be used for modulation of gut microbial ecology to promote health. 10.1016/j.chom.2018.05.012