Gastroenterology

Gastroenterology

Volume 146, Issue 6, May 2014, Pages 1525-1533
Gastroenterology

The Gut Microbiome and Disease
Role of the Microbiome in Energy Regulation and Metabolism

https://doi.org/10.1053/j.gastro.2014.02.008Get rights and content

Intestinal microbes regulate metabolic function and energy balance; an altered microbial ecology is believed to contribute to the development of several metabolic diseases. Relative species abundance and metabolic characteristics of the intestinal microbiota change substantially in those who are obese or have other metabolic disorders and in response to ingested nutrients or therapeutic agents. The mechanisms through which the intestinal microbiota and its metabolites affect host homeostasis are just beginning to be understood. We review the relationships between the intestinal microbiota and host metabolism, including energy intake, use, and expenditure, in relation to glucose and lipid metabolism. These associations, along with interactions among the intestinal microbiota, mucus layer, bile acids, and mucosal immune responses, reveal potential mechanisms by which the microbiota affect metabolism. We discuss how controlled studies involving direct perturbations of microbial communities in human and animal models are required to identify effective therapeutic targets in the microbiota.

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.).

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