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Understanding the pathogenesis of pouchitis
▸ Morgan XC, Kabakchiev B, Waldron L, et al. Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease. Genome Biol 2015:16:67. doi:10.1186/s13059-015-0637-x
Approximately 10%–35% of patients with UC will require colectomy with pouch reconstruction, and half of these patients will develop pouchitis. In addition, one-fifth will ultimately suffer pouch failure. Therefore, defining the basis of pouchitis is clearly of utmost importance. Similar to IBD, both host genetics and the microbiota are implicated in the pathogenesis of pouchitis. However, how these factors interact in this condition is not well understood. Interestingly, pouch construction is also performed for patients with familial adenomatous polyposis, although pouchitis is rare in this group. To investigate the basis of potential host–microbe interactions, this study by Morgan and colleagues collected paired host transcriptome and microbial metagenome data from a large J-pouch cohort. Modest associations between groups of host transcripts involved in inflammation including enrichment for complement cascade genes and the interleukin-12 pathway were identified. Activation of these pathways was inversely correlated with clades, including Sutterella, Akkermansia, Bifidobacterium and Roseburia, and positively correlated with Escherichia coli abundance. However, these associations did not account for the greatest sources of variation. Unsurprisingly, antibiotic usage was demonstrated as the strongest effect on gut microbiome differences. The transcriptome demonstrated large variation within individuals between presurgery and postsurgery samples while microbial communities remained consistent. The findings suggest that an individual's gut microbe composition may not be shaped by local transcriptional activity on a long-term basis. The findings point more to the influence of other factors, including diet and early-life events. The study also highlights the need for additional well-powered studies in this field to further our understanding.
The molecular basis of tumour resistance to chemotherapy
▸ Siravegna G, Mussolin B, Buscarino M, et al. Clonal evolution and …
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