- Researchers from Columbia University (USA) highlight the importance of Th17 cells in the prevention of metabolic diseases.

Several pieces of pastries, in a file image.

Sugar alters microbiome and removes protection against obesity and diabetes, study finds

It is known that a diet rich in fats and sugars can lead to metabolic diseases, diabetes, and overweight, but what happens in our body for this to happen? A study from Columbia University (United States) carried out on mice has discovered that sugar and the microbiome are to blame.

Precisely, dietary sugar alters the gut microbiome, setting off a chain of events that leads to metabolic disease, prediabetes, and weight gain. The results, published in Cell, suggest that diet is important, but an optimal microbiome is equally essential for the prevention of metabolic syndrome, diabetes, and obesity.

"A diet high in fats and sugars can lead to obesity, metabolic syndrome, and diabetes, but how the diet triggers unhealthy changes in the body is unknown," the researchers said.

The gut microbiome is critical to animal nutrition, so Dr. Ivalyo Ivanov, associate professor of microbiology and immunology at Columbia University's Vagelos College of Physicians and Surgeons, and colleagues investigated the early effects of the western-style diet on the microbiome of mice.

After four weeks on the diet, the animals showed features of metabolic syndrome, including weight gain, insulin resistance, and glucose intolerance. Furthermore, their microbiome had changed dramatically, as the number of segmented filamentous bacteria (common in the gut microbiota of rodents, fish, and chickens) was drastically reduced and the abundance of other bacteria increased.

Changes in the microbiome alter 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 gut, and further experiments revealed that it is Th17 cells that are needed to prevent metabolic diseases, diabetes, and weight gain.

"These immune cells produce molecules that slow down the absorption of 'bad' lipids from the intestine and decrease intestinal inflammation," says Ivanov. "In other words, they keep the intestine healthy and protect the body from the absorption of pathogenic lipids," he adds.

Sugar versus fat

But what component of the high-fat, high-sugar diet caused these changes? Ivanov's team discovered that it was sugar. "The sugar kills the filamentous bacteria and, as a consequence, the protective Th17 cells disappear," explains Ivanov.

"When we fed mice a high-fat, sugar-free diet, they preserved intestinal Th17 cells and were completely protected against developing obesity and prediabetes, even though they ate the same number of calories," he explains.

But removing the sugar didn't help all the mice. Among those that lacked any stringy bacteria, to begin with, removing the sugar had no beneficial effect, and the animals became obese and developed diabetes.

"This suggests that some popular dietary interventions, such as minimization of sugars, may only work in people who have certain bacterial populations within their microbiota," Ivanov adds.

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

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

Likewise, the supply of 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 underscores that a complex interplay between diet, 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."

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