Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response

• DOI: 10.1038/s41467-018-07841-3
• Publication Date: 2018-12-28T15:08:02Z
• Authors: Yael Haberman; Rebekah Karns; Phillip J. Dexheimer; Melanie Schirmer; Judith Somekh; Ingrid Jurickova; Tzipi Braun; Elizabeth Novak; Laura Bauman; Margaret H. Collins; Angela Mo; Michael J. Rosen; Erin Bonkowski; Nathan Gotman; Alison Marquis; Mason Nistel; Paul A. Rufo; Susan S. Baker; Cary G. Sauer; James Markowitz; Marian D. Pfeffer...; Joel R. Rosh; Brendan M. Boyle; David R. Mack; Robert N. Baldassano; Sapana Shah; Neal S. Leleiko; Melvin B. Heyman; Anne M. Grifiths; Ashish S. Patel; Joshua D. Noe; Bruce J. Aronow; Subra Kugathasan; Thomas D. Walters; Greg Gibson; Sonia Davis Thomas; Kevin Mollen; Shai Shen-Orr; Curtis Huttenhower; Ramnik J. Xavier; Jeffrey S. Hyams; Lee A. Denson
• Keywords: Pathogenesis; Gene signature

Abstract Molecular mechanisms driving disease course and response to therapy in ulcerative colitis (UC) are not well understood. Here, we use RNAseq define pre-treatment rectal gene expression, fecal microbiota profiles, 206 pediatric UC patients receiving standardised therapy. We validate our key findings adult paediatric cohorts of 408 participants. observe a marked suppression mitochondrial genes function across active UC, that increasing severity is notable for enrichment adenoma/adenocarcinoma innate immune genes. A subset improves prediction corticosteroid-induced remission the discovery cohort; this signature also associated with anti-TNFα anti-α 4 β 7 integrin adults. The therapeutic signatures were turn shifts microbes previously implicated mucosal homeostasis. Our data provide insights into pathogenesis, may prioritise future therapies nonresponders current approaches.