Editors' ChoiceMetabolism

Boosting Metabolism by Sweetening the Gut

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Science Translational Medicine  19 Feb 2014:
Vol. 6, Issue 224, pp. 224ec32
DOI: 10.1126/scitranslmed.3008647

Dietary fiber has beneficial effects on body weight and blood glucose control, but how fiber works to promote health remains unclear. Now, De Vadder et al. report that dietary fiber improves several aspects of metabolism through chemical signaling of the gut microbiota.

Soluble dietary fibers, such as galacto-oligosaccharides and fructo-oligosaccarides (FOS), are readily used by intestinal bacteria and converted to the short-chain fatty acids, acetate, propionate, and butyrate. Propionate, butyrate, and FOS are known to increase glucose tolerance and insulin sensitivity and to prevent rats from becoming overweight. However, the mechanisms underlying these effects are not well understood. De Vadder et al. show that rats fed propionate, butyrate, and FOS had increased production of glucose in the gut due to up-regulation of intestinal gluconeogenesis genes. Whereas butyrate could directly up-regulate genes, a neural circuit involving periportal nerve fibers, the propionate receptor (FFAR3), and discrete areas in the brainstem and spinal cord, was required for up-regulation by propionate. Using genetically modified mice, the authors show that the metabolic benefits caused by propionate, butyrate, and FOS only occurred in animals with normal intestinal gluconeogenesis genes. They conclude that intestinal gluconeogenesis genes are necessary for the beneficial metabolic effects of short-chain fatty acids and FOS. Last, the authors demonstrate that feeding FOS to mice with or without defects in intestinal gluconeogenesis genes resulted in pronounced alterations in the gut microbiota, with decreases in Firmicutes and increases in Bacteroidetes. As expected, the altered microbiota was associated with increases in short-chain fatty acids in portal and peripheral blood of both strains of mice.

The study by De Vadder et al. is important because it reveals a remarkable complexity in microbiota-host interactions and also provides new targets for therapeutic intervention for obesity and type II diabetes.

F. De Vadder et al., Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156, 84 (2014). [Abstract]

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