Editors' ChoiceHost-Microbe Interactions

Bugs–blood–brain–β cell signaling axis

Sci. Signal.  14 Jun 2016:
Vol. 9, Issue 432, pp. ec140
DOI: 10.1126/scisignal.aag3264

Short-chain fatty acids (SCFAs), such as acetate and butyrate, are bacterial metabolites that affect gut health and host metabolism. Changes in both fecal and plasma SCFA concentrations are associated with metabolic disorders. Perry et al. found that feeding rats or mice a high-fat diet (HFD) increased acetate concentrations in the plasma, feces, and brain. Metabolic labeling and experiments with antibiotics suggested that the excess acetate in HFD-fed rats was produced by the gut microbiota, and germ-free mice did not have acetate in their plasma or feces whether fed normal chow or a HFD. HFD or administration of acetate, but not butyrate, increased glucose-stimulated insulin secretion in rats. Transplanting fecal material from HFD-fed rats into rats fed normal chow increased whole-body acetate turnover and glucose-stimulated insulin secretion, whereas the reverse (fecal material from chow-fed rats into HFD-fed rats) normalized acetate turnover and glucose-stimulated insulin secretion. Pancreatic β cells secrete insulin in response to glucose or stimulation by the vagus nerve, part of the parasympathetic nervous system. Acetate did not induce β cells isolated from rats to secrete insulin, but injecting acetate into the brain increased glucose-stimulated insulin secretion. Furthermore, ligating the vagus nerve or treating rats with parasympathetic blockers prevented acetate from increasing glucose-stimulated insulin secretion. Chronic acetate treatment of rats fed a normal diet induced insulin resistance, ghrelin production, overeating, weight gain, and hypertriglyceridemia, but not if the vagus nerve was ligated before treatment. Thus, a HFD can promote obesity not just by providing the host with excess nutrients, but also by causing gut microbes to produce more acetate, which stimulates the parasympathetic nervous system to promote hyperinsulinemia and energy storage (see also Trajkovski and Wollheim).

R. J. Perry, L. Peng, N. A. Barry, G. W. Cline, D. Zhang, R. L. Cardone, K. F. Petersen, R. G. Kibbey, A. L. Goodman, G. I. Shulman, Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome. Nature 534, 213–217 (2016). [PubMed]

M. Trajkovski, C. B. Wollheim, Microbial signals to the brain control weight. Nature 534, 185–187 (2016). [PubMed]