The gut microbiome is closely related 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 person’s gut contains hundreds of different kinds of microbes, making it hard to tell which kind might help.
Now, research at the University of Utah has identified a specific type of gut bacteria, called Turicibacterthat improves metabolic health and reduces weight gain in mice fed a high-fat diet. Obese people tend to have less Turicibactersuggesting 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 Cellular Metabolism.
A tiny needle in a haystack
The researchers knew from previous work that a large group of about 100 bacteria were collectively able to prevent weight gain in mice, but finding a specific microbe that was key to weight maintenance was a painstaking task. “The microbes that live in our gut don’t like living outside the gut at all,” explains Kendra Klag, PhD, MD at the Spencer Fox Eccles School of Medicine at the University of Utah and first author of the paper. Many are killed by the presence of oxygen and must be handled exclusively in air-tight bubbles.
But after years of cultivating individual microbes, Klag found that a rod-shaped bacterium called Turicibacter could alone reduce blood sugar, blood fat levels, and weight gain for mice fed a high-fat diet.
“I didn’t think one microbe would have such a dramatic effect—I thought it would be a combination of three or four,” says June Round, PhD, professor of microbiology and immunology at U of U Health and senior author of the paper. “So when? [Klag] brought me the first experiment with Turicibacter and the mice were getting very thin, I said, “This is so amazing.” It’s very exciting when you see these kinds of results.”
Turicibacter appears to promote metabolic health by producing fat molecules that are absorbed by the small intestine. When researchers added purified Turicibacter fats on a high-fat diet, had the same weight control effects as Turicibacter himself. They don’t yet know which fat 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 the most important molecules in future work for potential therapeutic use.
A greasy feedback loop
Turicibacter appears to improve metabolic health by affecting the way the host produces a fatty molecule called ceramides, the researchers found. Ceramide levels increase in a high-fat diet, and high ceramide levels 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 affected by how much fat the host eats, the researchers found. The bacterium will not grow if there is a lot of 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 microbiome.
The results indicate a complex feedback loop in which a high-fat diet inhibits Turicibacter and fats produced by Turicibacter improve how the host responds to dietary fat.
Future directions
Researchers say that TuricibacterIts effects are unlikely to be unique. many different gut bacteria likely contribute to metabolic health. And results based on animal models may not apply to humans. “We’ve improved weight gain in mice, but I have no idea if that’s really true in humans,” Round says.
But they hope so Turicibacter could be a starting point for developing treatments that promote healthy metabolism and prevent excessive weight gain.
“Identifying the lipid that has this effect is going to be one of the most important future directions,” says Round, “both from a scientific point of view, because we want to understand how it works, and from a therapeutic point of view. Maybe we could use this bacterial lipid, which we know doesn’t have many side effects because people have it in their gut at a healthy weight.”
“By further investigating individual microbes, we will be able to turn microbes into drugs and find bacteria that are safe to create a consortium of different microbes that may be missing in people with different diseases,” Klag says. “Microbes are the ultimate wealth of drug discovery. We just know the tip of the iceberg of what all these different bacterial products can do.”
The results are published in Cellular Metabolism as “Dietary fat disrupts a 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 Diseases (grant numbers 5F30DK127846-04, R01DK124336, and R01DK123), and the National Center for Health and Supplemental (R01AT011423), as well as the Helmsley Foundation, the Burroughs Wellcome Fund, and the Keck Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
