Microbiome Gene Signatures Linked to Multiple Diseases

Microbiome Gene Signatures Linked to Multiple Diseases

Going a step deeper in understanding how the microbiome influences disease, researchers at Harvard Medical School and Joslin Diabetes Center found that a group of bacterial genes of gut microbes, or genetic signatures, is associated with multiple diseases.

The team determined that a set of microbiome disease architectures linked more than one million microbial features, including species, pathways, and genes with several diseases: adenoma, colorectal cancer, liver cirrhosis, inflammatory bowel diseases (IBD), type 2 diabetes, otitis, and atherosclerotic cardiovascular disease.

Their work to identify gene-level, cross-disease associations is published in Nature Communications.

They found  that a set of Streptococcal-specific bacterial genes was associated with three conditions — coronary artery disease, IBD, and liver cirrhosis. Other unique sets of bacterial genes were linked to the presence of coronary artery disease, cirrhosis of the liver, IBD, and colon cancer. Only type 2 diabetes had its own unique genetic signature unlike any of the other conditions in the study. Otitis and adenomas had only weak associations with the microbiome. Otitis was specifically chosen as a fairly reliable negative control.

“This opens a window for the development of tests using cross-disease, gene-based indicators of patient health,” said first author Braden Tierney, a graduate student in the Biological and Biomedical Sciences program at HMS. “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.”

The analysis was based on studying more than 2,500 samples from 13 patient groups.  Focusing on seven diseases, the sorted through genetic information regarding millions of microbial species, microbial metabolic pathways, and microbial genes. Ultimately sorting through 67 million statistical approaches they made the connections to identify microbiome features that consistently emerged as the strongest disease-associated candidates. Of all the various microbial characteristics — species, pathways, and genes — microbial genes had the greatest predictive power.

Earlier studies have reported a connection between Solobacterium moorei and colorectal cancer. Although that association was not consistently found on the species-level in this study, the researchers did observe a group of robust, S. moorei-specific gene associations associated with colorectal cancer.

The team validated their findings regarding colorectal cancer and IBD in samples from patient cohorts by finding that most of the top gene candidates observed in the model were found in patients.

“Overall, our work is not only a step towards gene-based, cross-disease microbiome diagnostic indicators, but it also illuminates the nuances of the genetic architecture of the human microbiome, including tension between gene- and species-level associations,” the authors say.

The team plans on further studies to see if these results could be used to design new tests to categorize a person’s risk for a range of conditions based on analysis of a single fecal sample.