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GutMicrobesandEndocrineCells

By James Porter,2015-04-02 21:15
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GutMicrobesandEndocrineCells

Gut Microbes and Endocrine Cells

    The gut communicates with the brain using endocrine signals to coordinate energy intake and expenditure. Enteroendocrine cells respond to nutrient intake by secreting incretin hormones, including glucagon-like peptides 1 and 2 (GLP-1 and GLP-2). GLP-1 stimulates insulin release from the pancreas, slows gastric emptying,

    [25•]and promotes satiety and weight loss;GLP-2 stimulates intestinal glucose

    [46]transport and reduces gut permeability. An earlier report indicated that gut

    microbiota can regulate enteroendocrine cells and influence the release of gut

    [47]hormones. Furthermore, the presence of microbes is necessary for the full

    [48]complement of enteroendocrine cells to be present in zebrafish. In a series of

    [49]studies, Cani et al.have shown a connection between gut microbes and levels of both GLP-1 and GLP-2. In rats, oligofructose treatment (which increases the proportion of Bifidobacteria) has been associated with a greater number of GLP-1 secreting enteroendocrine cells (L cells) in the colon. Ob/ob mice treated with

    prebiotic carbohydrates had altered gut microbiotas and increased levels of GLP-1

    [44] Thus, enteroendocrine cells represent a direct signaling pathway from and GLP-2.

    gut microbes to host metabolism.

    In yet another distinct pathway, gut microbes have been shown to stimulate gut

    [50]hormones. Samuel et al. recently showed that enteroendocrine cells express a

    receptor for SCFAs, GPR41, which is necessary for the full metabolic effect of these microbial metabolites. Mice lacking Gpr41 had reduced levels of the gut hormone

    PYY, greater gut transit time, lower recovery of SCFAs from the diet, and lower fat accumulation in fat pads. SCFAs are products of bacterial fermentation of carbohydrates from the diet: thus, they function both as an energy source and as a signaling molecule, and their abundance and type (e.g., butyrate, propionate, acetate) are directly related to the species composition of the microbiota and their syntrophic interactions. Again, it will be interesting to see whether other signaling pathways (such as through the SCFA receptor GPR43 for example) are similarly involved in host energy balance and whether different microbial communities interact differently with these molecules.

    Anecdotal evidence suggests that the gut microbes also affect gut hormones in humans. Gut hormones are implicated in the reduction of appetite and weight after

    [51,52]Roux-en-Y gastric bypass surgery (RYGP). In RYGP, a small gastric pouch is

    created from the proximal stomach and the distal stomach and proximal small

    intestine are bypassed. In a study of the effects of RYGP on the fecal microbes,

    [14•]Zhang et al. showed that members of the Gamma-Proteobacteria (and

    Verrucomicrobia) were enriched after gastric bypass, compared with lean and obese participants. In addition, the stomach chambers formed in RYGP surgery are

    [53]colonized by bacteria to a greater extent than the normal stomach.Interestingly,

    the administration of probiotic microbes after the procedure has been shown to

    [54]accelerate weight loss, supporting the notion that the gut bacteria may be

    modulating gut hormones.

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