Groundbreaking study shows link between sugar, gut and obesity

Dietary sugar alters the gut microbiome, setting off a chain of events that lead to metabolic disease, prediabetes, and weight gain. (CREDIT: Creative Commons)

A mouse study found that dietary sugar alters the gut microbiome, setting off a chain of events that lead to metabolic disease, prediabetes, and weight gain.

The results, published today in the journal Cell, show that diet matters, but an optimal microbiome is just as important in preventing metabolic syndrome, diabetes and obesity.

Diet changes the microbiome

A Western-style diet high in fat and sugar can lead to obesity, metabolic syndrome and diabetes, but it is not known how the diet triggers unhealthy changes in the body.

The gut microbiome is indispensable for animal nutrition, which is why Ivaylo Ivanov, MD, assistant professor of microbiology and immunology, Columbia University College of Physicians and Surgeons. Vagelos and colleagues investigated the initial impact of the Western diet on the microbiome of mice.

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After four weeks of the diet, the animals showed signs of the metabolic syndrome, such as weight gain, insulin resistance, and glucose intolerance. And their microbiomes have dramatically changed: the number of segmented filamentous bacteria common to the gut microbiota of rodents, fish and chickens has been dramatically reduced, while the number of other bacteria has increased.

Microbiome Changes Change Th17 Cells

Researchers have found that reducing filamentous bacteria is critical to animal health due to its effect on Th17 immune cells. The reduction in filamentous bacteria reduced the number of Th17 cells in the gut, and further experiments showed that Th17 cells are needed to prevent metabolic disease, diabetes, and weight gain.

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

Image of segmented filamentous bacteria in the mouse gut from Ivalho Ivanov, Columbia University Irving Medical Center.

Sugar versus fat

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

“Sugar destroys filamentous bacteria, and as a result, protective Th17 cells disappear,” says Ivanov. “When we fed mice a high-fat, sugar-free diet, they retained Th17 gut cells and were completely protected from developing obesity and prediabetes, despite consuming the same amount of calories.”

Microbiota-induced Th17 cells protect against diet-induced obesity and metabolic disease. Sugar destroys Th17 commensal cells, increasing the risk of metabolic disease. (CREDIT: Cellular)

But giving up sugar did not help all mice. In those initially deficient of filamentous bacteria, the elimination of sugar did not have a positive effect, and the animals became obese and developed diabetes.

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

In such cases, certain probiotics may help. In Ivanov mice, filamentous bacteria supplementation resulted in Th17 cell recovery and protection against metabolic syndrome, despite the animals consuming a high-fat diet.

While humans don’t have the same filamentous bacteria that mice do, Ivanov thinks that other bacteria in humans may have the same protective effect.

Giving mice Th17 cells has also provided protection and may be therapeutic in humans. “The microbiota is important, but the real protection comes from bacteria-induced Th17 cells,” says Ivanov.

“Our study highlights that the 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. “This suggests that for optimal health it is important not only to change your diet, but also to improve your microbiome or gut immune system, for example by increasing Th17 cell-inducing bacteria.”

To learn more about science and technology, visit our New Discoveries section at The bright side of the news.

Note. Materials provided by Columbia University Irving Medical Center. Content can be edited for style and length.

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