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Study indicates gut microbiome, host gene affect GI disorders

In a new study published in Nature Microbiology, researchers demonstrated the power of integrating the microbiome and host gene expression data tpo provide insights into their combined role in gastrointestinal diseases. The microbiome consists of all microbes in the gut including bacteria, fungi, and viruses. This study focused on bacteria.

"We identified a common set of host genes and pathways, including pathways that regulate gastrointestinal inflammation, gut barrier protection and energy metabolism that are associated with gut microbiome composition," says Ran Blekhman, Ph.D., a University of Minnesota researcher and corresponding author of the study.

The researchers studied 416 colonic mucosal samples from patients with colorectal cancer, inflammatory bowel disease and irritable bowel syndrome, in addition to nondisease controls. 

According to Purna Kashyap, M.B.B.S., a Mayo Clinic gastroenterologist, most studies focus on examining associations in a single disease at a time. As a result, common and unique patterns of host-microbiome associations across multiple disease states remain poorly characterized. Dr. Kashyap is a co-author of the study. 

"We found that gut microbes that have been previously implicated in all three diseases, including Streptococcus, associate with different host pathways in each disease," says Dr. Kashyap. "This suggests that both common and disease-specific interplay between gut microbes and host gene regulation may contribute to the underlying causes of gastrointestinal disorders."

The team developed a machine learning framework for integrating multi-omic high-dimensional datasets, such as host gene expression and gut microbiome abundance, to identify relevant host genes and pathways associated with gut microbes in each disease. They used this framework across the three diseases to find new insights into the molecular mechanisms underlying the causes of these gastrointestinal diseases.

"Gastrointestinal disorders are characterized by a complex network of associations between microbes and host genes," says Dr. Kashyap. "Our results represent an important step toward characterizing the association between the gut microbiome and host genomics data, providing invaluable information on the potential mechanisms through which the microbiome can affect health and the causes of disease."

"Although these associations can be disease-specific, we found cases where the same microbes are associated with different host genes in each disease and cases where the same host pathway is associated with different microbes in each disease."

The full listing of authors and their affiliations for this study is as follows:

  • Sambhawa Priya, Ph.D., Postdoctoral Associate at the Broad Institute at MIT and Harvard
  • Michael Burns, Ph.D.: Loyola University Chicago
  • Tonya Ward, Ph.D.: University of Minnesota
  • Ruben Mars, Ph.D.: Mayo Clinic
  • Beth Adamowicz, Ph.D.: University of Minnesota
  • Eric Lock, Ph.D.: University of Minnesota
  • Purna Kashyap, M.B.B.S.: Mayo Clinic
  • Dan Knights, Ph.D.: University of Minnesota
  • Ran Blekhman, Ph.D.: University of Minnesota

Competing Interests Statement

Dan Knights serves as senior scientific adviser to Diversigen, a company involved in the commercialization of microbiome analysis. Dr. Kashyap is an ad hoc consultant for Pendulum Therapeutics, IP Group Inc., Novome Biotechnologies Inc. and Intrinsic Medicine Inc. The remaining authors declare no competing interests.


Reprinted with permission from Mayo Clinic Center for Individualized Medicine

Posted 
May, 2022