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Sugar disrupts microbiome, removes protection against obesity and diabetes

Cell phone (2022). DOI: 10.1016/j.cell.2022.08.005″ width=”800″ height=”530″/>

Graphic abstract. Credit: Cell (2022). DOI: 10.1016/j.cell.2022.08.005

A study of mice found that dietary sugar ages the gut microbiome, triggering a chain of events that leads to metabolic disease, prediabetes, and weight gain.

The findings, published today in Cellsuggest that diet matters, but an optimal microbiome is equally important for the prevention of metabolic syndrome, diabetes, and obesity.

Diet Age Microbiome

A Western-style high-fat, high-sugar diet can lead to obesity, metabolic syndrome, and diabetes, but how the diet initiates unhealthy changes in the body is unknown.

The gut microbiome is indispensable to an animal’s nutrition, say Ivalyo Ivanov, Ph.D., associate professor of microbiology and immunology at Columbia University’s Vagelos College of Physicians and Surgeons, and colleagues investigated the early effects of Western-style diet on the microbiome of mice.

After four weeks on the diet, the animals showed features of the metabolic syndrome, including weight gain, insulin resistance, and glucose intolerance. And their microbiomes had changed dramatically, with the number of segmented filamentous bacteria, common in the gut microbiota of rodents, fish and chickens, dropping dramatically and other bacteria increasing in abundance.

Changes in the microbiome in altered Th17 cells

The researchers found that the reduction of filamentous bacteria was critical to the animals’ health through its effect on Th17 immune cells. The decrease in filamentous bacteria reduced the number of Th17 cells in the intestine, and further experiments revealed that it is the Th17 cells that are necessary to prevent metabolic diseases, diabetes and weight gain.

“These immune cells produce molecules that slow down the absorption of ‘bad’ lipids from the intestines and reduce intestinal inflammation,” says Ivanov. “In other words, they keep the gut healthy and protect the body from the absorption of pathogenic lipids.”

sugar vs fat

What component of the high-fat, high-sugar diet led to these changes? Ivanov’s team found that sugar was the culprit.

“The sugar kills the stringy bacteria, and as a consequence, the protective Th17 cells disappear,” says Ivanov. “When we fed mice a high-fat, sugar-free diet, they retained intestinal Th17 cells and were completely protected against developing obesity and prediabetes, despite consuming the same amount of calories.”

But cutting out the sugar didn’t help all the mice. For starters, among those lacking filamentous bacteria, removal of sugar had no beneficial effect, and the animals became obese and developed diabetes.

“This suggests that some popular dietary interventions, such as minimizing sugars, may only work in people who have certain bacterial populations within their microbiota,” says Ivanov.

In those cases, certain probiotics might be helpful. In Ivanov’s mice, supplementation of filamentous bacteria led to recovery of Th17 cells and protection against metabolic syndrome, despite the animals’ consumption of a high-fat diet.

Although people don’t have the same stringy bacteria as mice, Ivanov thinks other bacteria in people may have the same protective effects.

Providing Th17 cells to mice also provided protection and may also be therapeutic for people. “The microbiota is important, but the real protection comes from the bacteria-induced Th17 cells,” says Ivanov.

“Our study emphasizes that a complex interplay between diet, the microbiota, and the immune system plays a key role in the development of obesity, metabolic syndrome, type 2 diabetes, and other conditions,” says Ivanov. “It suggests that for optimal health it is important not only to modify the diet, but also to improve the gut microbiome or immune system, for example by increasing Th17 cell-inducing bacteria.”


A low-calorie diet alters the gut microbiome and delays immune aging


Information:
Yoshinaga Kawano et al, Dietary sugar-induced microbiota imbalance disrupts immune-mediated protection against metabolic syndrome, Cell (2022). DOI: 10.1016/j.cell.2022.08.005

Diary information:
Cell


Provided by Columbia University Irving Medical Center


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