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October 4, 2022
Western-style diets, which are high in fat and sugar, are linked to weight gain. In turn, excess weight and obesity can lead to metabolic diseases such as type 2 diabetes. The mechanisms in the body that underlie these relationships aren’t fully understood. They’re thought to involve the immune system and the microbes that live in the gut.
NIH-funded researchers led by Dr. Ivaylo Ivanov from Columbia University have been using mice to look at these complex relationships. In their new study, they carefully compared mice fed a diet high in fat and sugar with mice fed a low-sugar diet. Results were published on September 15, 2022, in Cell.
Mice fed a chow high in fat and sugar gained weight compared with mice fed a normal grain-based chow. They also developed early signs of diabetes. After only a week on the high-fat, high-sugar diet, the mice had changes in the immune cells in their guts. Notably, they had fewer Th17 immune cells, which are thought to help protect against weight gain and metabolic problems.
Previous studies have shown that a specific type of bacteria in the gut called segmented filamentous bacteria promotes the production of Th17 cells in mice. The team found that, in mice fed the high-fat, high-sugar diet, levels of these bacteria decreased sharply, followed by a drop in production of Th17 cells.
When the researchers engineered mice unable to produce Th17 cells, the presence of the helpful bacteria didn’t protect the animals from weight gain and signs of metabolic disease. Conversely, when the researchers restored Th17 cells into the mice, the mice maintained a healthy weight and didn’t develop early signs of diabetes. Transplanting the helpful bacteria into normal mice on the high-fat, high-sugar diet had a similar protective effect.
Further work implicated sugar—specifically sucrose, a major component of table sugar—as driving these effects. When mice with the helpful bacteria were fed a high-fat diet where all of the sugar was replaced with starch, they remained at a healthy weight and didn’t develop early signs of diabetes. When mice on this sugar-free diet received sucrose in their drinking water, their Th17 cells dropped, and they gained weight.
The researchers next looked at changes in the gut microbes of mice on the high-sugar diet. They found that dietary sucrose greatly increased the amount of bacteria from a family called Erysipelotrichaceae in the gut. These bacteria, in turn, appeared to push out the helpful bacteria that trigger Th17 cell production.
Finally, the researchers looked at how Th17 cells might help prevent weight gain and metabolic disease. They found that, normally, Th17 cells help slow the uptake of certain dietary fats into intestinal cells and decrease inflammation in the gut. Without the Th17 cells, fat absorption and gut inflammation increased.
“Our study emphasizes that a complex interaction between diet, microbiota, and the immune system plays a key role in the development of obesity, metabolic syndrome, type 2 diabetes, and other conditions,” Ivanov says.
Gut microbes differ between people and mice. However, an analysis of past studies found that adults with metabolic syndrome had fewer gut microbes known to induce the production of Th17 cells. More work is needed to understand the effects of dietary sugar on gut microbes in humans.
—by Sharon Reynolds
References: Microbiota imbalance induced by dietary sugar disrupts immune-mediated protection from metabolic syndrome. Kawano Y, Edwards M, Huang Y, Bilate AM, Araujo LP, Tanoue T, Atarashi K, Ladinsky MS, Reiner SL, Wang HH, Mucida D, Honda K, Ivanov II. Cell. 2022 Sep 15;185(19):3501-3519.e20. doi: 10.1016/j.cell.2022.08.005. Epub 2022 Aug 29. PMID: 36041436.
Funding: NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), and National Institute of Biomedical Imaging and Bioengineering (NIBIB); Burroughs Wellcome Fund; MSD Life Science Foundation; Russell Berrie Foundation; Naomi Berrie Diabetes Center; Japan Society for the Promotion of Science; National Science Foundation; Irma T. Hirschl Trust.
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How diet may disrupt gut microbes to promote weight gain – National Institutes of Health (.gov)
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Oct 11, 2022