Changes to Gut Microbiome May Increase Type 2 Diabetes Risk

The composition of the gut microbiome may affect the likelihood of developing type 2 diabetes, according to the largest and most ethnically and geographically comprehensive study of its kind to date.

Scientists investigated the gut microbiome — the collection of bacteria, fungi, and viruses in our intestines — of people with type 2 diabetes, prediabetes, or healthy blood glucose levels. They found that specific viruses and genetic variants within bacteria correspond with changes in gut microbiome function and an increased risk of type 2 diabetes.

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If further research confirms that these changes indeed contribute to the development of type 2 diabetes, researchers could use that knowledge to try to manipulate the microbiome to reduce type 2 diabetes risk, the authors said.

Research over the past decade had linked changes in the gut microbiome to the development of type 2 diabetes, but scientists had not been able to draw significant conclusions because of those studies’ small size and varied design.

“The microbiome is highly variable across different geographic locations and racial and ethnic groups. If you only study a small, homogeneous population, you will probably miss something,” said co-corresponding author Daniel (Dong) Wang, Harvard Medical School assistant professor of medicine at Brigham and Women’s Hospital.

“The gut microbiome's relationship to complex, chronic, heterogeneous diseases like type 2 diabetes is quite subtle,” added co-corresponding author Curtis Huttenhower, professor of computational biology and bioinformatics at the Harvard T.H. Chan School of Public Health and the Broad Institute of MIT and Harvard. “Large and diverse populations are necessary — and increasingly feasible — for detailed microbiome variation studies.”

The new study, a collaboration between researchers at HMS, Brigham and Women’s, the Broad Institute, and Harvard Chan School, published June 25 in Nature Medicine.

Drawing connections

In type 2 diabetes, which affects approximately 537 million people worldwide, a person’s body gradually loses its ability to effectively regulate blood sugar. Although prior research has connected changes in the gut microbiome to type 2 diabetes, a diverse large-scale study has been lacking.

To address this need, researchers analyzed data from the newly established Microbiome and Cardiometabolic Disease Consortium (MicroCardio). The dataset included genomic information from the gut microbiomes of 8,117 people. Participants had type 2 diabetes, prediabetes, or normal blood glucose levels, and were ethnically and geographically diverse, hailing from the United States, Israel, Sweden, Finland, Denmark, Germany, France, and China.

The researchers found a consistent set of microbial species that were linked to type 2 diabetes across their study populations, including many that had never been reported before. To understand the role of these microbes in the gut, the researchers analyzed the species’ functional abilities. They found that certain strains of microbes had functions that may be linked to varied type 2 diabetes risk.

For example, a strain of Prevotella copri — a common gut microbe ​​that has the capacity to produce large quantities of branched-chain amino acids — was more commonly seen in the gut microbiomes of people with type 2 diabetes. Previous studies have shown that people with chronically high levels of branched-chain amino acids in their blood have a higher risk of obesity and type 2 diabetes.

The researchers also found evidence suggesting that bacteriophages — viruses that infect bacteria — could be driving some of the changes they detected within certain strains of gut bacteria.

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

The team also studied a small subset of samples from people newly diagnosed with type 2 diabetes, whose microbiomes were less likely to have been affected by medication use or long-term high glucose levels. The results were similar to the broader findings of the study.

“We believe that changes in the gut microbiome cause type 2 diabetes — the changes to the microbiome may happen first, and diabetes develops later, not the other way around,” said Wang, who is also an assistant professor in the department of nutrition at the Harvard T.H. Chan School of Public Health. He pointed out, however, that prospective or interventional studies are needed to confirm this relationship.

If the relationship is confirmed, Wang thinks that it may be possible to reduce risk of type 2 diabetes by altering the microbiome.

“The microbiome is amenable to intervention, meaning you can change your microbiome, for example, with dietary changes, probiotics, or fecal transplants,” he said.

A major limitation of the study is that it primarily looked at patients' microbiomes at one point in time, rather than looking at changes to the microbiome or disease status over time. Thus, further studies are needed that assess how changes over an extended period lead to type 2 diabetes.

“A benefit and a challenge of the human microbiome is that it is highly personalized,” Huttenhower said. “Very large population studies are needed to find consistent patterns, but once we do, individual microbiomes have the potential to be reshaped to help reduce disease risk.”

Adapted from a Brigham and Women’s news release.