Published in the journal Nature Communications, their groundbreaking finding highlighted the impact of a high-fat diet on gut bacteria. In particular, the team found that, compared with healthy mice, obese mice have fewer intestinal immune cells that produce the antibody, immunoglobulin A (IgA).
Meanwhile, mice deficient in IgA-producing intestinal immune cells that were fed a high-fat diet exhibited dysfunctional glucose metabolism. These results suggest that the intestinal immune system is a major contributor to obesity-related insulin resistance.
Obesity is marked by the abnormal accumulation of excess body fat. The presence of too much fat, particularly in the abdominal area, is said to upset the gut microbial balance and stimulate other factors that promote gut inflammation and the onset of insulin resistance.
To shed light on the mechanisms behind these events, researchers from Canada, Taiwan and the U.S. studied the changes in gut immunity caused by a high-fat diet and obesity using a mouse model and human stool samples from bariatric surgery patients.
The researchers found that feeding obese mice a high-fat diet disturbed their gut microbial composition and significantly reduced the amount of IgA-producing B cells -- a type of immune cells -- in their intestines. B cells are important components of the intestinal immune system and are crucial to regulating the bacteria that thrive in the gut.
As an antibody, IgA serves as the gut's first line of defense against harmful bacteria that might take advantage of metabolic changes, such as those triggered by the consumption of fatty foods. Therefore, having inadequate amounts of B cells and IgA can pose serious health risks.
For instance, the researchers found that feeding obese, IgA-deficient mice a high-fat diet caused the animals' blood glucose levels to rise and exacerbated their insulin resistance. The intestines of IgA-deficient mice also became permeable, meaning harmful bacteria and toxins could easily pass through the intestinal walls and enter the bloodstream.
When the researchers transplanted gut bacteria isolated from IgA-deficient mice into gut microbiota-depleted mice, they found that the latter developed insulin resistance. These results suggest that IgA is the missing link that connects poor diet and obesity to insulin resistance.
To check if their findings were also true for humans, the researchers analyzed stool samples from 14 adults taken before and after bariatric surgery. They reported a significant increase in these individuals' intestinal IgA levels after the procedure. (Related: Patients of weight-loss surgery are at triple the death risk from substance use, study says.)
This finding mirrors the results of their animal study, which showed that obese mice had fewer IgA-producing B cells than healthy mice. This also suggests that diet influences gut immunity, particularly the production of intestinal IgA, which is linked to metabolic function and the risk of metabolic conditions like insulin resistance.
According to senior author Daniel Winer, their next objective is to determine how to increase the amount of IgA-producing B cells in deficient individuals. He and his colleagues believe this strategy will not only improve gut immunity, but also help prevent insulin resistance by suppressing intestinal inflammation.