Among the worst things about coming back to work after summer holidays is acknowledging you have gained some extra weight. Too much indulgence, you may guiltily think. But is that the whole story? According to new research published in the journal Nature, your gut microbiota might have had a role to play.
Several studies have already linked changes in the microbial community inhabiting the intestines to metabolic diseases, such as obesity and insulin resistance. Nevertheless, the mechanisms underlying this relationship—and whether it is causal—remained unclear.
Now, a study led by Yale and Howard Hughes Medical Institute researchers may shed light on the subject. Researchers found that some microbe-made molecules in mice tell the brain to change digestion and to boost insulin and ghrelin, the so-called hunger hormone, thus prompting you to eat more.
The hint to discovering this chain of events came from a previous study. Researcher Gerald Shulman, M.D., from Yale School of medicine and Howard Hughes Medical Institute, was conducting an experiment and observed that acetate, which is a short-chain fatty acid, stimulated the secretion of insulin in rodents; insulin tells the fat cells to store more energy, which leads to fat build-up and, ultimately, to obesity. Shulman also saw that high-fat diets elevated levels of acetate in the animals’ blood.
To learn more, the research team decided to conduct new experiments with mouse models of obesity. First, they discovered that animals fed with a high-fat diet presented elevated levels of acetate.
Secondly, for 10 days they directly injected acetate into the rodents’ brains and saw the animals turned into obese “eating machines”, secreting more insulin and also ghrelin.
They saw that acetate did not directly stimulate pancreatic cells to produce insulin; instead this molecule triggered a signal from the brain to the pancreas through the vagus nerve -a major nerve connecting the brain with internal organs- to increase the production of insulin. In fact, when the researchers cut the vagus nerve or blocked its function with drugs, acetate did not elevate insulin levels.
“Acetate stimulates beta cells to secrete more insulin in response to glucose through a centrally mediated mechanism. It also stimulates the secretion of hormones gastrin and ghrelin, which lead to increased food intake”, says Shulman in a statement.
Finally, in germ-free mice raised in sterile conditions and rodents treated with antibiotics to eliminate their gut microbes, researchers saw that the animals did not produce much acetate. But, when they transferred in fecal matter to restore their gut microbes, the production of acetate and insulin were again stimulated.
“Taken together these experiments demonstrate a causal link between alterations in gut microbiota in response to changes in the diet and increased acetate production”, says Shulman in a statement. And the increased acetate in turn leads to increased food intake, setting off a positive feedback loop that drives obesity and insulin resistance, he adds. This does not mean acetate causes obesity in humans, however; the picture is complicated because the gut microbiota rapidly transform acetate into other short-chain fatty acids. The beneficial or detrimental effects of acetate are still debated in the scientific community.
The next step, researchers say, will be to examine whether this mechanism they have discovered in rodents, explaining how an altered gut microbiota is linked to obesity and metabolic syndrome, could be translated to humans.
References:
Perry, RJ, et al. Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome. Nature. 2016; 534:213–217. DOI: 10.1038/nature18309
