New Research Reveals Gut Microbiome-Diabetes Link

The role of altered gut microbiota on functions, ranging from hormone secretion to metabolic function, remains unclear.

New research on the gut microbiome and the pancreas could lead to new treatments for diabetes and other diseases.

In the study published in the journal Diabetes,1 a team of researchers from Boston College and Maastricht University in the Netherlands investigated the role of gut microbes on pancreas function using mouse models of obesity and diabetes.

The investigators found that alterations in gut microbiota in obesity can alter pancreatic growth, exocrine function, and gut endocrine function and may contribute to the alterations observed in patients with obesity and diabetes.

“Our results are quite novel and very exciting. To our knowledge, this is the first study showing that gut microbes play this important role in regulating pancreas function, size and secretion of gut hormones in mice,” said Emrah Altindis, co-author of the report and assistant professor of biology at Boston College, in a Boston College news release.2

While previous studies have shown that the composition of the gut microbiota alters with these diabetes and obesity, the role of altered gut microbiota on the host functions—ranging from hormone secretion to metabolic functions—remain unclear, Boston College said.

The pancreas was the central focus because the organ secretes hormones that regulate host metabolism as well as enzymes for digestion and its function is impaired in diabetes, Altindis said.

The team utilized two commonly used antibiotics—vancomycin and metronidazole—to “remodel” the gut microbiota in mice that had been fed a high-fat diet and a control group fed a balanced food chow product.

All mice on the high-fat diet became obese, compared to the control group. A subgroup of the obese mice was treated either with the vancomycin or metronidazole antibiotics—which effectively remodeled the gut microbiota—and while this sub-group remained obese, these mice showed increased insulin sensitivity.

The mice with remodeled gut microbiota were less diabetic, and more glucose tolerant compared to obese mice that did not receive the antibiotics, said Altindis.

Likewise, antibiotics treatment made lean mice even more insulin sensitive.

“This consistency in our results in both lean and obese mice suggest that the effects on host metabolism are independent from the diet and/or fat mass, but directly related to the altered gut microbiota composition,” Altindis said.

The high-fat diet increased the size of the pancreas in the obese mice group. However, after antibiotic treatment, the pancreas size returned to normal. “Notably, pancreatic enzymes essential to digestion were altered by the high-fat diet but returned to normal levels or were further altered following antibiotic treatment,” the press release noted.

This alteration of pancreatic enzymes was specific to “obese” mice and it was not observed in the lean mice, indicating that lean mice did not have similar alterations in pancreas function with the antibiotics, Altindis said. The finding further confirmed the harmful effects of a high-fat diet on pancreatic function.

Among obese mice treated with antibiotics, the team found that gut hormones produced by the gastrointestinal system—which are central to regulating metabolism—returned to normal levels comparable to those of lean mice.

In order to test that the effects on gut hormones are 100% gut microbiota-driven, the researchers turned to a germ-free mouse model, one that does not carry any microbes, Altindis said.

“When we transferred the gut microbiota of antibiotic-treated mice to germ-free mice gut, they showed all the effects observed in the donor mice, proving that gut microbes are responsible for these effects on the gut hormones and directly regulating host gut hormone production processes,” Altindis said.

The team then replicated the findings in human patients. They studied fecal samples obtained from men with insulin resistance and obesity who had been treated with vancomycin for 1 week.

“We showed that 1 week of vancomycin treatment was sufficient to alter their pancreas enzyme levels, a very similar result to our findings in mice,” Altindis said. “We are working on follow up studies to better understand the underlying mechanisms and identify specific bacterial species and products leading these functional alterations.”

Importantly, the findings have the potential to help develop novel gut microbiota-based therapies to normalize pancreas function in obese diabetes patients, according to Altindis.

The research was supported by the National Institutes of Health, the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases, the G. Harold & Leila Y. Mathers Foundation, Joslin Diabetes Center, and TI Food and Nutrition of the Netherlands.

References

  1. Girdhar K, Soto M, Huang Q, et al. Gut microbiota regulate pancreatic growth, exocrine function, and gut hormones. Diabetes. 2022;71(5):945-960. doi:10.2337/db21-03822.
  2. Diabetes researchers find gut microbiota regulate pancreatic growth, exocrine function, and gut hormones. News release. Boston College. April 13, 2022. Accessed May 2, 2022. https://www.eurekalert.org/news-releases/949597