Studies on chronic inflammatory disease and the human microbiome move WAY beyond just species composition:

The human microbiome (Image: https://www.biocote.com)

Several times this past year I’ve been told that studies connecting microbiome dysbiosis (imbalance) to chronic inflammatory disease “haven’t moved beyond association.” I disagree. In fact, for years now, teams have been using computer modeling, metabolomics and a range of other methods to dissociate “cause from effect” in microbiome-based analyses. These three 2018 studies are excellent examples of the trend (while they involve the gut microbiome, similar studies have been also been conducted on microbiome ecosystems in other body sites):

Gut microbiota composition and functional changes in inflammatory bowel disease and irritable bowel syndrome

Lead author: Rinse K. Weersma, University of Groningen and University Medical Center Groningen

The team characterized gut microbiome dysbiosis in patients with IBD/IBS using a computer-based tool called shotgun sequencing. BUT, they also analyzed bacterial taxonomy, metabolic functions, antimicrobial resistance genes, virulence factors, and growth rates. Thanks to this extra information, they were able to identify key bacterial species that may be involved in both disorders.

Pathogenic Functions of Host Microbiota

Lead author: Marius Vital, Helmholtz Centre for Infection Research, Germany

Co-occurrence analysis of individual pathofunctions (Vital et al)

The team studied the gut microbiome, and found that different groups of bacteria often exhibit redundant pathogenic functions (they called them “pathofunctions”). These pathofunctions include the production of common metabolites (like trimethylamine, secondary bile acids, and hydrogen sulfide). This functional redundancy has implications for the study of chronic inflammatory disease tied to microbiome dysbiosis: it suggests that metabolic dysfunction driven by different groups of organisms can result in similar clusters of inflammatory symptoms. 

Distinct Microbes, Metabolites, and Ecologies Define the Microbiome in Deficient and Proficient Mismatch Repair Colorectal Cancers

Lead author: Nicholas Chia, The Ohio State University College of Veterinary Medicine

The team combined tumor biology, metagenomics, metabolomics and modeling approaches to study the impact of the gut microbiome on colon cancer. They demonstrated distinct roles for microbes and their metabolites in colon cancer mismatch repair status. For example, highly influential microbes included many butyrate producers.