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WGO Handbook on Diet and the Gut_2016_Final

World Digestive Health Day WDHD – May 29, 2016 ALESSIO FASANO, MD Director Mucosal Immunology and Biology Research Center Massachusetts General Hospital for Children Boston, Massachusetts, USA STATE OF THE ART Microbial cells in the human body outnumber human cells by about ten to one. The vast majority of these reside in the gastrointestinal tract. Non-culture based technologies have evolved over the past several years, revolutionizing the feasibility and accuracy of the human microbiome analysis. There had been longstanding belief that the fetus resides in a sterile environment, but this has been challenged in recent years with microbial discoveries in both the placenta and meconium1 thanks to these advanced technologies. It is also now well established that mode of delivery, maternal diet, infant diet, antibiotic exposure, and the home environment can all have significant impact on the early development of the infant intestinal microbiome2 (See Figure 1). The intestinal microbiome of the infant and young child is susceptible to dramatic shifts secondary to environmental exposures until 1-3 years of age. This implies that disruptions in normal, healthy microbiota development in infancy can have lasting effects even in adulthood.3 Increased hygiene and a lack of exposure to various microorganisms have been held responsible for the “epidemic” of chronic inflammatory diseases that over the past 30-40 years has been recorded in industrialized countries. That is the essence of the hygiene hypothesis that argues that rising incidence of asthma, inflammatory bowel disease (IBD), multiple sclerosis, type 1 diabetes, irritable bowel syndrome (IBS), celiac disease (CD), and other chronic inflammatory diseases may be, at least in part, the result of lifestyle and environmental changes that have made us too “clean” for our own good. The hygiene hypothesis, first proposed by Greenwood in 1968 and subsequently by Strachan in 1989, suggested lack of early childhood infections in the developed world might be responsible for this rise in allergic and autoimmune diseases.4 Over the past several years, knowledge of the human microbiome has been rapidly accelerating thanks to the Human THE HUMAN GUT MICROBIOME Microbiome Project Initiative. As our understanding of the human microbiome expands, the hygiene hypothesis continues to be revised and frequently challenged and was recast more recently as the “microflora hypothesis.”5 This suggested that Western lifestyle alters exposure to microbes (rather than infection per se), causing perturbations in the colonization of the intestinal mucosa and affecting mucosal immune system development and predisposition to cause inflammation through mechanisms that are still being elucidated, and thus increasing the risk for chronic diseases. Specifically, there is mounting evidence suggesting that microbiome-mediated maturation of gut epithelial barrier and of the immune system impact capacity for the host to develop responses that maintain immune tolerance and prevent aberrant pro-inflammatory or allergic responses. Indeed, it appears that there is a two-way connection between the microbiota and immune dysfunction, with both influencing and shaping each other, and a complex relationship maintained to ensure homeostasis. Additionally, by causing increased gut permeability, gut dysbiosis may lead to passage of endotoxins and/or food- Figure 1: Factors influencing the epidemics of chronic inflammatory diseases by affecting microbiome composition. Prenatal, perinatal, and postnatal factors play a key role in shaping gut microbiome composition and, in turn, the proper maturation of the gut associated lymphoid tissue (GALT) to exert either a tolerogenic or pro-inflammatory function that, together with genetic predisposition, may lead to a state of health or diseases, respectively. 50 WGO Handbook on DIET AND THE GUT World Digestive Health Day WDHD May 29, 2016


WGO Handbook on Diet and the Gut_2016_Final
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