Gauging disease risk by studying the gut microbiome's genetic features

Stomach with colon
Scientists at Harvard Medical School found links between the gut microbiome's genetic signatures and diseases such as coronary artery disease, inflammatory bowel disease and liver cirrhosis. ( Images)

Recent research suggests that microorganisms living in the human gut may play a role in diseases ranging from obesity to cancer. A team at Harvard Medical School has gone one step further, linking the microbiome’s genetic features to multiple diseases.

By using a variety of statistical models and machine learning, the Harvard scientists identified what they call “microbiome architectures” behind human diseases. They linked several sets of genetic features of the microbiome to many conditions, including coronary artery disease, inflammatory bowel disease, liver cirrhosis, Type 2 diabetes and others, according to a new study published in Nature Communications.

The findings could inform the design of tests that could more accurately predict disease risk based on bacterial genetic markers rather than merely the presence of certain bacterial species, the team suggested.

For the study, the researchers collected microbiome data from 13 groups of patients that contributed a total of 2,573 samples. After running the data against several models, they found that genetic features had the strongest associations with diseases. Microbial metabolic pathways and the species of microbe also had some role, but the associations weren't nearly as strong. This means that genetic architecture is a better predictor of disease than the mere existence of certain bacteria is, the researcher said.

The team found gene clusters in different human diseases. Coronary artery disease, inflammatory bowel disease and liver cirrhosis shared similar genetic signatures, the team found, suggesting that a person whose gut harbors those bacterial genes may be prone to developing all three conditions.

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The bacterium Solobacterium moorei had the most genes linked to disease, including IBD, atherosclerotic cardiovascular disease and colorectal cancer.

Previous studies have reported a link between S. moorei and colorectal cancer. But the Harvard team didn’t find a consistent link between the species and the cancer; instead, they that found genes in a particular S. moorei strain called F0204 were closely related to colorectal cancer, and genes from other bacteria, such as those from Firmicutes bacterium and Gemella haemolysans, also appear to play a part in the disease.

Other research groups have demonstrated the impact of gut microbial composition on diseases beyond the gastrointestinal tract. A team led by the Johannes Gutenberg-University Mainz in Germany recently found that interleukin-17, in its ability to regulate gut microbiome, may be a critical driver of multiple sclerosis.

Researchers at Baylor College of Medicine showed that the microbe-based probiotic Limosilactobacillus reuteri or a metabolite of it could restore normal social behavior in mice with a brain disease similar to autism.

Identification of genetic architectures in the microbiome could help guide the development of high-throughput diagnostic tools for specific diseases, the Harvard team suggested. 

“This opens a window for the development of tests using cross-disease, gene-based indicators of patient health,” Branden Tierney, the study’s first author, said in a statement. “We've identified genetic markers that we think could eventually lead to tests, or just one test, to identify associations with a number of medical conditions.”