New discovery reveals how sugar disrupts gut bacteria, leading to obesity
A new animal study has demonstrated one way sugar can contribute to metabolic diseases such as diabetes is by causing disruptions to the gut microbiome. The novel findings home in on exactly how certain gut bacteria can protect against the harmful effects of a high-fat diet, and how dietary sugar can disrupt those protective mechanisms.
It’s certainly not breaking news to suggest a high-fat, high-sugar diet can lead to a variety of health problems. But as scientists learn more about the ways trillions of bacteria in our gut can influence our general health we are also gathering some unique insights into exactly how poor dietary choices are causing particular health problems.
In this new study, researchers first focused on what a high-fat, high-sugar diet did to the microbiome of mice, with an eye on a specific kind of immune cell. Called Th17, these immune cells are a specialized subset of T cells that help protect the gut from certain pathogenic bacteria. Low levels of Th17 cells has been associated with metabolic disease and inflammatory conditions.
“These immune cells produce molecules that slow down the absorption of ‘bad’ lipids from the intestines and they decrease intestinal inflammation,” explained Ivaylo Ivanov, lead researcher on the project. “In other words, they keep the gut healthy and protect the body from absorbing pathogenic lipids.”
So what happened to Th17 cells in mice guts when fed high-fat, high-sugar diets? The animals rapidly developed several characteristics of metabolic disease (weight gain, glucose intolerance), and showed reductions in gut Th17 cells.
But even more specifically, the researchers discovered the reduction in Th17 levels was due to diet-induced changes to the gut microbiome. Bacteria known to promote Th17 were replaced by other species of gut bacteria. And it was sugar in particular that seemed to increase populations of harmful gut bacteria that ultimately lowered levels of Th17.
Interestingly, Ivanov said as long as the animals retained high levels of gut bacteria known to induce Th17, a fatty diet did not lead to negative metabolic effects.
“Sugar eliminates the filamentous bacteria, and the protective Th17 cells disappear as a consequence,” said Ivanov. “When we fed mice a sugar-free, high-fat diet, they retain the intestinal Th17 cells and were completely protected from developing obesity and pre-diabetes, even though they ate the same number of calories.”
However, any metabolic health benefits gained by removing sugar from the mouse diet were only apparent in the presence of Th17-inducing gut bacteria. Without that particular microbial composition the animals on adjusted high-fat, low-sugar diets still gained weight and developed metabolic syndrome.
“This suggests that some popular dietary interventions, such as minimizing sugars, may only work in people who have certain bacterial populations within their microbiota,” Ivanov added.
According to Ivanov, some people may benefit from probiotics that help boost levels of Th17-inducing gut bacteria. But because mouse microbiomes are different to humans, it is unclear exactly what types of bacteria would be optimal, and even with that knowledge a targeted probiotic would only be useful in scenarios where clinicians could be sure a person would need these particular microbes.
Perhaps the most overt takeaway from the findings is that one of the ways dietary sugar can lead to metabolic problems is by changing Th17 levels in the gut. And Ivanov speculates a future where Th17 is directly therapeutically targeted, instead of trying to modulate the bacterial middlemen.
“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 said. “It suggests that for optimal health it is important not only to modify your diet but also improve your microbiome or intestinal immune system, for example, by increasing Th17 cell-inducing bacteria.”
The new study was published in Cell.