Study links changes in gut microbiome to increased risk of type 2 diabetes

The largest and most ethnically and geographically comprehensive investigation to date of the gut microbiome of people with type 2 diabetes (T2D), prediabetes, and healthy glycemic status, found that specific viruses and genetic variants within bacteria correspond to changes in gut microbiome function and T2DM. risk.

The results of the study, which represents a collaboration between Brigham and Women’s Hospital, the Broad Institute of MIT and Harvard, and the Harvard TH Chan School of Public Health, are published in Natural medicine.

“The microbiome is highly variable across geographic areas and racial and ethnic groups. If you only study a small, homogenous population, you’ll likely miss something,” said co-corresponding author Daniel (Dong) Wang, MD, ScD , of the study. Channing Division of Network Medicine at Brigham and Women’s Hospital, Broad and Harvard Chan School. “Our study is by far the largest and most diverse study of its kind.”

“The relationship of the gut microbiome to complex, chronic, and heterogeneous diseases like T2D is quite subtle,” said co-corresponding author Curtis Huttenhower, Ph.D. of the Harvard Chan School and Broad. “Just as studies of large human populations have been crucial to understanding human genetic variation, large and diverse populations are also necessary – and increasingly feasible – for detailed studies of microbiome variation.”

T2D affects approximately 537 million people worldwide. In T2D, the body gradually loses its ability to effectively regulate blood sugar. Research over the past decade has linked changes in the gut microbiome (the collection of bacteria, fungi, and viruses that inhabit our intestines) to the development of T2D. However, previous studies of the gut microbiome and its role in T2D have been too limited and varied in design to draw meaningful conclusions.

This article analyzed data from the new Microbiome and Cardiometabolic Disease Consortium (MicroCardio). The survey included newly generated data and those initially captured during several other experiments, encompassing a total of 8,117 gut microbiome metagenomes from ethnically and geographically diverse participants.

People included in the study had T2DM, prediabetes, or no changes in their blood sugar levels and were from the United States, Israel, Sweden, Finland, Denmark, Germany , from France and China. Co-first authors of the paper are Zhendong Mei, Ph.D., of the Channing Division of Network Medicine at Brigham and Women’s Hospital and Broad, as well as Fenglei Wang, Ph.D., of the Harvard Chan School and Broad.

“As part of this large study, we asked two questions. The first is: ‘What are the roles of the species and strains that make up the gut microbiome in type 2 diabetes?’ The other question is: ‘What are these microbes doing?'” Wang said. “When we analyzed these data, we found a relatively consistent set of microbial species linked to type 2 diabetes in our study populations. Many of these species have never been reported before.”

To understand the role of these microbes in the gut, the team analyzed the functional capacities of the species. Different strains of a microbial species can have varying functions, such as the ability to make a specific amino acid. The team found that certain strains had functions that could be linked to varying risk of T2DM.

A major functional difference they found was that a strain of Prevotella copri – a common microbe in the gut that has the ability to produce large amounts of branched-chain amino acids (BCAAs) – was more frequently seen in the intestinal microbiomes of diabetic patients. Previous studies have shown that people with chronically high blood levels of BCAA are at higher risk of obesity and T2DM.

The researchers also found evidence to suggest that bacteriophages – viruses that infect bacteria – could be behind some of the changes detected within certain strains of gut bacteria.

“Our findings regarding bacteriophages were very surprising,” Wang said. “This could mean that the virus infects the bacteria and changes its function in a way that increases or decreases the risk of type 2 diabetes, but more work is needed to understand this link.”

In another analysis, the team studied a small subset of samples from patients newly diagnosed with T2D to assess microbiomes that are less likely to have been affected by medication use or high blood sugar. long-term. Their results were similar to their broader findings, according to Wang.

“We think changes in the gut microbiome cause type 2 diabetes,” Wang said. “Changes in the microbiome may occur first, and diabetes will develop later, not the other way around, although future prospective or interventional studies are needed to firmly prove this relationship.”

“If these microbial features are causal, we may find a way to modify the microbiome and reduce the risk of type 2 diabetes,” he added. “The microbiome is amenable to intervention, meaning you can change your microbiome, for example with dietary changes, probiotics or fecal transplants.”

A major limitation of the study is that, for the most part, it looked at patients’ microbiome at a single point in time. It did not look at changes in the gut microbiome or disease status over time. Future studies that build on this work include investigating this link over an extended period of time and examining strain-specific functions to better understand how they lead to T2D.

“An advantage and challenge of the human microbiome is that it is highly personalized,” Huttenhower said. “The fact that we each have very distinct microbial communities and microbial genetics means that very large population studies are needed to find consistent patterns. But once we do, individual microbiomes have the potential to be remodeled to help reduce the risk of disease.”