Mucosal microbiota and gene expression are associated with long-term remission after discontinuation of adalimumab in ulcerative colitis

Abstract

Given that sustained remission is the ultimate treatment goal in the management of patients with ulcerative colitis (UC), the decision to stop anti-tumor necrosis factor (anti-TNF) treatment in UC patients is difficult. The aim of this study was to evaluate mucosal microbiota and gene expression profiles associated with long-term remission after discontinuation of anti-TNF therapy. In nine UC patients who received anti-TNF therapy for 6 months, microbiota isolated from uninflamed mucosae and gene expression in inflamed and uninflamed mucosae were investigated at week 0 and at week 24. At treatment initiation, Fusobacterium sp. and Veillonella dispar were over-represented in the relapse group compared with the non-relapse group. After treatment, Dorea sp. and Lachnospira sp. were over-represented in the non-relapse group. In the relapse group only, a significant shift in gut bacterial community composition was found between week 0 and week 24. Gene expression of ALIX (PDCD6IP) and SLC9A3 was significantly higher in the non-relapse group than in the relapse group. Lastly, we used machine learning methods to identify relevant gene signatures associated with sustained remission. Statistical analyses of microbiota and expression profiles revealed differences between UC patients who did or did not keep remission after the discontinuation of TNF inhibitors. Trial registration: UMIN000020785: Evaluation of adalimumab therapy in mesalazine-resistant or -intolerant ulcerative colitis; an observational study (EARLY study).

Correlation Between the Gut Microbiome and Immunotherapy Response in Inflammatory Bowel Disease: A Systematic Review of the Literature

“…One observational/non-randomized control trial was excluded on the basis of insufficient quality. The study findings of the included studies are summarized in Table 3 [ 3 , 28 - 37 ].…”

“…Gene expression in both the host and the gut microcosm interact with environmental stressors to create a favorable (or unfavorable) condition for the development of inflammatory autoimmune diseases. A study by Sakurai et al evaluated the association between long-term remission in UC after discontinuation of anti-TNF therapy, mucosal microbiota, and gene expression profiles [ 28 ]. They used machine learning with IBD GWAS data as a predictive tool in a similar method as is used to predict cancer susceptibility, recurrence, and survivability [ 28 ].…”

“…A study by Sakurai et al evaluated the association between long-term remission in UC after discontinuation of anti-TNF therapy, mucosal microbiota, and gene expression profiles [ 28 ]. They used machine learning with IBD GWAS data as a predictive tool in a similar method as is used to predict cancer susceptibility, recurrence, and survivability [ 28 ]. UC follows a relapsing and remitting course where machine learning, as a predictive tool, could advise patients on therapy discontinuation [ 28 ].…”

“…They used machine learning with IBD GWAS data as a predictive tool in a similar method as is used to predict cancer susceptibility, recurrence, and survivability [ 28 ]. UC follows a relapsing and remitting course where machine learning, as a predictive tool, could advise patients on therapy discontinuation [ 28 ]. They found that gene expression in the non-relapse UC group had substantially higher gene expression of ALIX, also known as programmed cell death 6-interacting protein (PDCD6IP), and ​​​​SLC9A3(Solute carrier family 9 member A3) compared with the relapse group [ 28 ].…”

“…UC follows a relapsing and remitting course where machine learning, as a predictive tool, could advise patients on therapy discontinuation [ 28 ]. They found that gene expression in the non-relapse UC group had substantially higher gene expression of ALIX, also known as programmed cell death 6-interacting protein (PDCD6IP), and ​​​​SLC9A3(Solute carrier family 9 member A3) compared with the relapse group [ 28 ]. Furthermore, it is speculated that expression of ALIX, IL22RA (interleukin-22 receptor subunit alpha-1), LGR6 (leucine-rich repeat-containing G protein-coupled receptor 6), and SLC9A3 may prevent UC flares since these genes were downregulated after anti-TNF therapy in the relapse group while in heat shock proteins and ITGA7 (integrin alpha 7) were upregulated in this group [ 28 ].…”