Research Overview by Dr. Katie Golden MD: Dynamics of Metatranscription in the Inflammatory Bowel Disease Gut Microbiome (Schirmer M., et al., Nat Microbiol. 2018 Jan 8)

Scientists have identified several genetic mutations implicated in Inflammatory Bowel Disease (IBD), and recent research has focused on defining those environmental factors that affect expression of these genes. Over the past decade, investigators have to come to realize that the gut microbiome plays a central role in IBD development and progression. The relationship between variations in gut microbial communities and aberrant immune responses, however, remains enigmatic, and therefore has been a focus of study for immunologists, biologists, and clinical researchers alike.

The Human Microbiome Project is an attempt to understand how dynamic fluctuations in the microbiome affect IBD pathophysiology by collecting and analyzing longitudinal data of over 100 individuals over 1 year. In this study, Schirmer present the first results from this initiative, and in turn discover that it is not only abundance of bacterial populations, but also their activity that play a critical role in IBD phenotypic variation. They compared the functional potential of gut microbial communities (from shotgun metagenomics, aka DNA) to a direct measure of functional activities (from metatranscriptomics, aka RNA) in fecal samples from both IBD and control individuals over a year, and highlight the importance of both bacterial abundance and activity in IBD progression.

Researchers found dramatic differences in transcriptional behavior in gut microbial species, encouraging the importance of measuring both functional potential and activity together. D.invisus, for example, has been detected in the gut microbiome of IBD patients specifically, and while its DNA abundance was comparable to other significant microbial communities, it was largely absent from the metatranscriptomic data, suggesting it is a dead or dormant population. F.prausnitzii, a species prevalent in the microbiome of all patients, had large longitudinal fluctuations in RNA abundances despite fairly stable abundance over time. When researchers looked at disease-specific microbial populations found specifically in Crohn’s Disease (CD) and Ulcerative Colitis (UC) patients, they found that certain species were only detectable at the transcript level (B.vulgatus and A.putredinis, for example). Other populations, such as R.gavnus, had significantly increased RNA abundance in CD and UC patients despite minor only minor increases in DNA abundance, suggesting that it is a change in their activity, not abundance, that has implications for IBD disease progression.

These preliminary findings from the Human Microbiome Project show the inadequacy of relying solely on variations in microbial population abundance to better understand IBD. With a multidimensional approach, both by studying microbial transcription activity as well collecting longitudinal data in individuals over time, we can greatly enhance our understanding of the microbiome’s contribution to IBD pathophysiology.