How altered gut microbes cause obesity

Study reveals how altered gut microbes cause obesity

June 8, 2016
Obesity is linked to changes in our gut microbes — the trillions of tiny organisms that inhabit our intestines. But the mechanism has not been clear. In a new study published in Nature, a Yale-led team of researchers has identified how an altered gut microbiota causes obesity.

In an earlier study, Dr. Gerald I. Shulman, the George R. Cowgill Professor of Medicine, observed that acetate, a short-chain fatty acid, stimulated the secretion of insulin in rodents. To learn more about acetate’s role, Shulman, who is also an investigator of the Howard Hughes Medical Institute, and a team of Yale researchers conducted a series of experiments in rodent models of obesity.

The research team compared acetate to other short-chain fatty acids and found higher levels of acetate in animals that consumed a high-fat diet. They also observed that infusions of acetate stimulated insulin secretion by beta cells in the pancreas, but it was unclear how.

Next, the researchers determined that when acetate was injected directly into the brain, it triggered increased insulin by activating the parasympathetic nervous system. “Acetate stimulates beta cells to secrete more insulin in response to glucose through a centrally mediated mechanism,” said Shulman. “It also stimulates secretion of the hormones gastrin and ghrelin, which lead to increased food intake.”

Finally, the research team sought to establish a causal relationship between the gut microbiota and increased insulin. After transferring fecal matter from one group of rodents to another, they observed similar changes in the gut microbiota, acetate levels, and insulin.

“Taken together these experiments demonstrate a causal link between alterations in the gut microbiota in response to changes in the diet and increased acetate production,” said Shulman. The increased acetate in turn leads to increased food intake, setting off a positive feedback loop that drives obesity and insulin resistance, he explained.

The study authors suggest that this positive feedback loop may have served an important role in evolution, by prompting animals to fatten up when they stumbled across calorically dense food in times of food scarcity.

“Alterations in the gut microbiota are associated with obesity and the metabolic syndrome in both humans and rodents,” Shulman noted. “In this study we provide a novel mechanism to explain this biological phenomenon in rodents, and we are now examining whether this mechanism translates to humans.”

Additional authors include Rachel J. Perry, Liang Peng, Natasha A. Barry, Gary W. Cline, Dongyan Zhang, Rebecca L. Cardone, Kitt Falk Petersen, Richard G. Kibbey, and Andrew L. Goodman.

This study was funded by grants from the Howard Hughes Medical Institute, the National Institutes of Health, and the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.

http://news.yale.edu/2016/06/08/study-reveals-how-altered-gut-microbes-cause-obesity

Great stuff as always, Yoly. The next step should be to look at what dietary factors produce these changes in gut microbiota.

The research is in infancy and is very complex. Everything you eat or drink affect your microbe eco system. Every time you poop you lose gut bacteria. Your gut eco system is unique is not just the history of your food, water, medications and every environment exposure you had but also your mother and father.

Increasing the production of butyric acid help and that can be increased by more fiber. But is complex because is an eco system and what is good or bad depend on the eco system you have. Like a animal kingdom eco system a predator can be good or bad depending if you have too little or too much it can affect the balance and do harm. The same with gut microbes you have both "good" and "bad" bacteria's if you feed them the results may vary since it is an eco system the results may be unpredictable.

One major thing I noticed was that not only low carbing but giving up wheat seems to have had permanent and long lasting improvements on my gut functioning. Very occasionally I miss a day or two but even then when the turd arrives it is nothing out of the ordinary. Can't remember when I last had the squits.

Purely from the functioning point of view my gut flora and I seem to be singing off the same hymn sheet.

It took careful work by a dietician removing every trace of fat from my diet and replacing it with carbs before I finally gained some weight, so she could then accuse me of "failing to comply" with the diet. On the other side I just visited the supermarket and the night staff were mostly under 30. Hardly any of them weren't fat. I bet they all eat low fat.

Thinking about it further, a lot of research is pointing at gut microbes, and also mitochondria, which could be said to be bacteria living within our cells that produce our energy for us. Maybe we are just containers for a community of other life.