The gut bacteria that put the brakes on weight gain in mice

(Press-News.org) The gut microbiome is intimately linked to human health and weight. Differences in the gut microbiome—the bacteria and fungi in the gut—are associated with obesity and weight gain, raising the possibility that changing the microbiome could improve health. But any given person’s gut contains hundreds of different microbial species, making it difficult to tell which species could help.

Now, research at the University of Utah has identified a specific type of gut bacteria, called Turicibacter, that improves metabolic health and reduces weight gain in mice on a high-fat diet. People with obesity tend to have less Turicibacter, suggesting that the microbe may promote healthy weight in humans as well. The results could lead to new ways to control weight by adjusting gut bacteria.

The results are published in Cell Metabolism.

A microscopic needle in a haystack The researchers had known from previous work that a large group of about 100 bacteria was collectively able to prevent weight gain in mice, but finding a specific microbe that was key to weight maintenance was a laborious task. “The microbes that live in our gut don’t like to live outside the gut at all,” explains Kendra Klag, PhD, MD candidate at the Spencer Fox Eccles School of Medicine at the University of Utah and first author on the paper. Many are killed by the presence of oxygen and must be exclusively handled in airtight bubbles.

But after years of culturing individual microbes, Klag found that a rod-shaped bacterium called Turicibacter could single-handedly reduce blood sugar, levels of fat in the blood, and weight gain for mice on a high-fat diet.

“I didn’t think one microbe would have such a dramatic effect—I thought it would be a mix of three or four,” says June Round, PhD, professor of microbiology and immunology at U of U Health and senior author on the paper. “So when [Klag] brought me the first experiment with Turicibacter and the mice were staying really lean, I was like, ‘This is so amazing.’ It’s pretty exciting when you see those types of results.”

Turicibacter appears to promote metabolic health by producing fatty molecules that are absorbed by the small intestine. When the researchers added purified Turicibacter fats to a high-fat diet, they had the same weight-controlling effects as Turicibacter itself. They don’t yet know which fatty molecules are the important part—the bacterium produces thousands of different fats, in what Klag describes as a “lipid soup”—but they hope to narrow down on the most important molecules in future work for potential therapeutic use.

A fatty feedback loop Turicibacter appears to improve metabolic health by affecting how the host produces a fatty molecule called ceramides, the researchers found. Ceramide levels increase on a high-fat diet, and high levels of ceramides are associated with many metabolic disorders, including type 2 diabetes and heart disease. But the fats produced by Turicibacter are able to keep ceramide levels low, even for mice on a high-fat diet.

Turicibacter levels are themselves affected by how much fat the host eats, the researchers discovered. The bacterium won’t grow if there’s too much fat in its environment, so mice fed a high-fat diet will lose Turicibacter from their gut microbiome unless their diet is regularly supplemented with the microbe.

The results point to a complex feedback loop, in which a fatty diet inhibits Turicibacter and fats produced by Turicibacter improve how the host responds to dietary fats.

Future directions The researchers say that Turicibacter’s effects are unlikely to be unique; many different gut bacteria probably contribute to metabolic health. And results based in animal models may not apply to people. “We have improved weight gain in mice, but I have no idea if this is actually true in humans,” Round says.

But they’re hopeful that Turicibacter could provide a starting point for developing treatments that promote healthy metabolism and prevent excessive weight gain.

“Identifying what lipid is having this effect is going to be one of the most important future directions,” Round says, “both from a scientific perspective because we want to understand how it works, and from a therapeutic standpoint. Perhaps we could use this bacterial lipid, which we know really doesn't have a lot of side effects because people have it in their guts, as a way to keep a healthy weight.”

“With further investigation of individual microbes, we will be able to make microbes into medicine and find bacteria that are safe to create a consortium of different bugs that people with different diseases might be lacking,” Klag says. “Microbes are the ultimate wealth of drug discovery. We just know the very tip of the iceberg of what all these different bacterial products can do.”

###

The results are published in Cell Metabolism as “Dietary fat disrupts a commensal-host lipid network that promotes metabolic health.”

This work was supported by the National Institutes of Health, including the National Cancer Institute (grant number F32CA243501), the National Institute of Diabetes and Digestive and Kidney Disorders (grant numbers 5F30DK127846-04, R01DK124336, and R01DK124317), and the National Center for Complementary and Integrative Health (R01AT011423), as well as the Helmsley Foundation, the Burroughs Wellcome Fund, and the Keck Foundation. Content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

END