Details

Autor(en) / Beteiligte

• Haberman, Yael
• Karns, Rebekah
• Dexheimer, Phillip J
• Schirmer, Melanie
• Somekh, Judith
• Jurickova, Ingrid
• Braun, Tzipi
• Novak, Elizabeth
• Bauman, Laura
• Collins, Margaret H
• Mo, Angela
• Rosen, Michael J
• Bonkowski, Erin
• Gotman, Nathan
• Marquis, Alison
• Nistel, Mason
• Rufo, Paul A
• Baker, Susan S
• Sauer, Cary G
• Markowitz, James
• Pfefferkorn, Marian D
• Rosh, Joel R
• Boyle, Brendan M
• Mack, David R
• Baldassano, Robert N
• Shah, Sapana
• Leleiko, Neal S
• Heyman, Melvin B
• Grifiths, Anne M
• Patel, Ashish S
• Noe, Joshua D
• Aronow, Bruce J
• Kugathasan, Subra
• Walters, Thomas D
• Gibson, Greg
• Thomas, Sonia Davis
• Mollen, Kevin
• Shen-Orr, Shai
• Huttenhower, Curtis
• Xavier, Ramnik J
• Hyams, Jeffrey S
• Denson, Lee A

Titel

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

Ist Teil von

• Nature communications, 2019-01, Vol.10 (1), p.38-13, Article 38

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

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