The Gut Microbiome and DiseaseRole of the Microbiome in Energy Regulation and Metabolism
Section snippets
Alteration of the Gut Microbiota in Obesity and Diabetes
The intestinal microbiota is altered in humans and animal models of obesity.31 The intestinal (cecum-derived) microbiota of ob/ob mice has a 50% reduction in levels of Bacteroidetes and an increased proportion of Firmicutes compared with wild-type mice.32 The composition of the fecal microbiota of obese human subjects is similarly affected but changes with weight loss.33 Studies in germ-free mice provide insights into the effects of the intestinal microbiota on host metabolism. Germ-free mice
Microbiota and Bile Acids
Bile acids are secreted as glycine, taurine, or sulfate conjugates. Compounds excreted in bile reach the intestinal tract, where they can be deconjugated by gut microbiota, aided by populations of microorganisms with their own hydrolytic enzymes such as β-glucuronidase and sulfatases.39 Most liver-secreted bile acids (95%) are reabsorbed in the ileum to be taken up by the liver in the enterohepatic cycle. Only a small part of the bile acid pool escapes the enterohepatic cycle and travels toward
Intestinal Microbiota and Host Physiology and Diseases
Recent advances in sequencing technology and large-scale information processing have increased our understanding of the diversity of the intestinal microbiota and its relationship to host physiology and diseases. Comprehensive characterizations of the microbiota have revealed rapid and profound effects of environmental and physiological changes on the composition and metabolic activities of the microbiota. Conversely, the microbial ecology has been correlated with specific diseases such as
Luminal Factors That Regulate Host Metabolism
Commensal gut bacteria regulate immune and metabolic functions via several mechanisms.55 Bacteria release fatty acids, peroxidases, proteases, and bacteriocins that prevent pathogens from expanding in the intestinal community7; as previously mentioned, bacterial disaccharidases ferment unabsorbed dietary carbohydrates into SCFAs. Although increased generation of SCFAs could increase energy uptake from ingested plant carbohydrates, recent studies have shown that higher levels of SCFAs are
Therapeutic Potential of the Microbiota
The large amount of evidence that a healthy microbiota is required for human health and protects against disease has led to much interest in its therapeutic potential. Fecal microbial transplantation (FMT) has been shown to be an effective therapy for recurrent or refractory Clostridium difficile–induced colitis; its success in early trials has led to more widespread use.
The ability of the microbiota to transfer metabolic phenotypes among mice indicates the potential of FMT and related
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by the 2012 EU RESOLVE Consortium (grant FP7-EU 305707 to P.W.G.), National Institutes of Health grant DK088661 (to L.M.K.), and a Heart and Stroke Foundation of Canada Junior Personnel Grant (HSFCR5 to N.P.).