What is already known
A high-fat, high-sugar diet can lead to metabolic syndrome — a series of conditions, including excess weight, high cholesterol, high blood pressure and high sugar levels, that predispose a person to developing diabetes and cardiovascular diseases. Some studies suggested that alterations in the gut microbiota are a risk factor for metabolic syndrome, but how gut microbes influence the condition is poorly understood.
What this research adds
Working in mice, researchers found that a high-fat, high-sugar diet changes the composition of the mice’s gut microbiota dramatically, with the levels of beneficial bacteria declining sharply. The drop in these bacteria resulted in reduced gut levels of specific immune cells that regulate the absorption of fatty molecules across the intestinal barrier and decrease intestinal inflammation. Further analyses showed that high sugar was responsible for the decrease in beneficial bacteria.
Conclusions
The findings suggest that the interplay between diet, microbiota and intestinal immunity regulates obesity, diabetes and other metabolic conditions.
A high-fat, high-sugar diet can lead to metabolic syndrome — a series of conditions, including excess weight, high cholesterol, high blood pressure and high sugar levels, that predispose a person to developing diabetes and cardiovascular diseases. These conditions may be the result of alterations of the gut microbiota that are triggered by dietary sugar, according to a new study in mice.
The findings, published in Cell, suggest that the interplay between diet, microbiota and intestinal immunity regulates obesity, diabetes and other metabolic conditions. The results also indicate that “for optimal health it is important not only to modify your diet but also improve your microbiome or intestinal immune system,” says study senior author Ivaylo Ivanov at Columbia University.
Previous studies suggested that alterations in the gut microbiota are a risk factor for metabolic syndrome, but how gut microbes influence the condition is poorly understood. To address this question, Ivanov and his colleagues investigated the effects of a high-fat, high-sugar Western-style diet on the microbiota of mice.
Western diet
After four weeks on the diet, the mice showed weight gain and high levels of blood glucose, which are characteristics of metabolic syndrome. The animals also showed changes in their gut microbiotas.
In the guts of mice fed a Western-style diet, the levels of filamentous bacteria declined sharply, whereas other bacteria increased in abundance. In mice, filamentous bacteria are known to induce specific immune cells called Th17 cells, which play a key role in the intestinal barrier integrity as well as in immune responses.
Microbiota-induced Th17 cells regulate the absorption of fatty molecules across the intestinal barrier and decrease intestinal inflammation, the researchers found. The loss of protective Th17 cells was mediated by the presence of sugar in the mice’s diet.
High sugar
When the mice were fed a low-sugar, high-fat diet, they retained the intestinal Th17 cells and were protected from obesity and metabolic syndrome, the researcher found.
However, mice lacking filamentous bacteria in their guts didn’t appear to benefit from the low-sugar, high-fat diet, as they developed metabolic syndrome and gained excess weight. “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.
Sugar also promoted the growth of Faecalibaculum rodentium — a commensal bacterium found in the mice gut — that displaced Th17-inducing bacteria in the gut. These findings, the authors say, “highlight an elaborate interaction between diet, microbiota, and intestinal immunity in regulation of metabolic disorders.”
