Middle aged man with type 2 diabetes using blood sugar measurement device to monitor type 2 diabetes, which can be linked to changes in the gut microbiome.
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A study of more than 8,000 gut microbiome profiles sampled from people in eight different countries led by researchers based at Harvard University shows abnormal changes in 19 bacterial species are linked to increased risk of developing type 2 diabetes.

Of the 19 gut bacteria species identified, five were linked with type 2 diabetes alone and 14 with prediabetes and type 2 diabetes.

As reported in Nature Medicine, examples of the bacteria present at abnormal levels were higher levels of Clostridium bolteae and depleted Butyrivibrio crossotus. Low levels of the latter have been linked to obesity.

“The gut microbiome’s relationship to complex, chronic, heterogeneous diseases like type 2 diabetes is quite subtle,” said co-lead author Curtis Huttenhower, PhD, a professor at Harvard Chan School and the Broad Institute, in a press statement.

“Much like studies of large human populations have been crucial for understanding human genetic variation, large and diverse populations are necessary—and increasingly feasible—for detailed microbiome variation studies as well.”

Gut microbiome signatures have previously been linked to diabetes, but the small sizes and varying analytic approaches of previous studies mean that earlier results are inconsistent.

This study included microbiomes sampled from 8,117 people (54% female)—1,851 with type 2 diabetes, 2,770 with prediabetes, and 2,277 control participants with normal blood sugar. To try and make the results as diverse as possible, the samples came from people in the United States, Israel, Sweden, Finland, Denmark, Germany, France and China.

“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-lead author Daniel (Dong) Wang, an assistant professor at Brigham and Women’s Hospital, the Broad Institute, and Harvard Chan School of Public Health. “Our study is by far the largest and most diverse study of its kind.”

The investigators linked abnormal levels of 19 bacterial species to type 2 diabetes and/or prediabetes.  Of these, 14 species had not previously been identified, while five had been linked to type 2 diabetes in earlier research. The latter included higher levels of Clostridium citroniae, Clostridium bolteae and Escherichia coli, and lower levels of Coprococcus eutactus and Turicibacter sanguinis in people with type 2 diabetes.

The previously unidentified species included two oral Streptococcus species and Bacteroides fragilis all of which were higher in people with type 2 diabetes and are thought to trigger or add to inflammation in the body.

Prevotella copri—which produces large amounts of branched-chain amino acids (BCAAs)—was also high in people with high blood sugar. High levels of BCAAs have been linked to obesity and type 2 diabetes in the past.

“We believe that changes in the gut microbiome cause type 2 diabetes,” said Wang. “The changes to the microbiome may happen first, and diabetes develops later, not the other way around—although future prospective or interventional studies are needed to prove this relation firmly.”

This study is a step forward in collecting data on how the gut microbiome influences the development of this type of diabetes. More research is still needed, however. For example, studying how the gut microbiome changes over time in relation to diabetes risk or development would be very useful.

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