Researchers Reveal Only a Modest Association Between Gene Expression and Microbiota in IBD Patients

Researchers Reveal Only a Modest Association Between Gene Expression and Microbiota in IBD Patients

shutterstock_227398606A study recently published in the journal Genome Biology analyzed the possible association between host gene expression, the mucosal microbiota and clinical outcome in patients with inflammatory bowel disease (IBD). The study was led by researchers at Harvard T. H. Chan School of Public Health, The Broad Institute of MIT and Harvard, and Zane Cohen Centre for Digestive Diseases in Toronto and is entitled “Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease.

IBD is a chronic inflammatory condition of the digestive tract that primarily comprises ulcerative colitis and Crohn’s disease. It is characterized by vomiting, abdominal pain, rectal bleeding, diarrhea, internal cramps in the pelvis region, fatigue and weight loss. It is estimated that 10 to 35% of patients with ulcerative colitis, will eventually require a colectomy (surgical removal of all or part of the colon) with subsequent ileal pouch-anal anastomosis (IPAA) construction, also known as “J pouch” (a surgical procedure to restore gastrointestinal continuity after colectomy). Half of the patients submitted to IPAA surgery due to ulcerative colitis will, however, experience at least one episode of pouchitis, an inflammation of the ileal pouch. Both microbiota and host genetics are thought to be involved in the development of pouchitis, although it is not clear how these host-microbe interactions are established.

In order to determine the relationship between the mucosal IPAA microbiota, host gene expression and clinical outcome, data from host transcriptome and microbial metagenome from a large cohort of patients submitted to IPAA at Mount Sinai Hospital in Toronto, Canada was analyzed.

Researchers found that host gene expression (in terms of RNA transcripts) varied primarily depending on biopsy location (pouch vs pre-pouch ileum). On the other hand, the mucosal microbiota varied primarily depending on the antibiotic use. Transcript-microbe associations were found to be only modest, with the strongest ones involving complement cascade genes and the interleukin-12 pathway. Host transcripts involved in inflammation were found to have a modest inverse association with Sutterella, Akkermansia and Bifidobacterium microbiota and a positive correlation with Escherichia abundance.

The research team concluded that gut host gene expression is not a major determinant of the pouch microbiota composition and that these two variables seem to be influenced by distinct factors. The authors believe that since the associations between gene expression and microbiota were found to be modest, other factors, like diet and initial host colonization, most likely influence the microbiota composition.