Pairwise Comparison of the Gut Microbiome in Microscopic Colitis

We presented our microscopic colitis microbiome data preliminary results, more info can be found here. This work was later published, see our paper Microscopic Colitis is Characterized by Intestinal Dysbiosis for more information.

Abstract

Microscopic colitis is thought to result in part from inappropriate immuneresponse to the gut microbiota in genetically susceptible hosts. However, longitudinal altera-tions in gut microbiota in microscopic colitis have not been previously examined.Methods:We analyzed the stool microbiota from 11 patients with a median age of 62 years (range:24-92) with microscopic colitis during both active and remission phase (22 samples, cohorts1 and 2) and compared these to 11 age- and sex-matched controls from patients withchronic diarrhea without microscopic colitis or inflammatory bowel disease (cohort 3) usingshotgun metagenomic sequencing with a depth of 10-15 million reads per sample. At thetime of enrollment, participants had not used antibiotics for at least 3 months. Speciesand metabolic pathway abundances were estimated using MetaPhlAn2 and HUMAnN2,respectively. Species richness was assessed using alpha diversity and we calculated betadiversity utilizing the Bray-Curtis method and principal coordinate analysis (PCoA) usingmultidimensional scaling (MDS). We used multivariate association with linear models (MaAs-Lin) to identify species and metabolic pathways that significantly differ between active andremission samples while adjusting for other metadata.Results:The 50 most prevalentspecies from the three cohorts are summarized in a heatmap (Figure 1). We observed astatistically significant difference in species richness as measured by alpha diversity whencomparing active vs. remission states in microscopic colitis (P= 0.0038,Figure 2A). Chronicdiarrhea controls had greater species richness compared to patients with active microscopiccolitis, although the comparison did not reach statistical significance (P= 0.08,Figure 2A).Disease status was the single most influential factor in determining microbial communitystructure as measured by PCoA (Figure 2B). Several species, includingEggerthella lentaandHaemophilus parainfluenzae, and key metabolic pathways, including chorismate biosynthesisfrom 3-dehydroquinate and adenosine deoxyribonucleotides de novo biosynthesis II, weresignificantly different between the active and remission states. The difference, however, didnot reach statistical significance after adjusting for multiple comparisons using false discoveryrate.Conclusion:The gut dysbiosis central to active microscopic colitis more closely resem-bles inflammatory bowel disease than non-inflammatory diarrhea. Larger-scale studies arerequired to further characterize individual species and microbiota-encoded metabolic changesin active microscopic colitis.

Figures can be seen here