Gene expression alterations in ulcerative colitis patients after restorative proctocolectomy extend to the small bowel proximal to the pouch

Yanai, Henit; Ben‐Shachar, Shay; Baram, Liran; Elad, Hofit; Gitstein, Gilad; Brazowski, Eli; Tulchinsky, Hagit; Pasmanik‐Chor, Metsada; Dotan, Iris

doi:10.1136/gutjnl-2014-307387

Cited by 26 publications

(16 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding suggested that mucosal inflammation may not be limited to endoscopic lesions in the gut, and that molecular abnormalities may better diagnose an impairment of intestinal homeostasis and subclinical intestinal inflammation. Consistent with these results, a previous study demonstrated that there were marked overlaps in the gene expression alterations between the small bowel proximal to the pouch and the pouch itself in patients with UC following restorative proctocolectomy (23).…”

Section: Discussionsupporting

confidence: 81%

Gene expression alterations in inflamed and unaffected colon mucosa from patients with mild inflammatory bowel disease

Lian

et al. 2016

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. An endoscopic examination is currently the most reliable method for monitoring disease activity in patients with inflammatory bowel disease (IBD). However, endoscopic evaluations are unable to detect mucosal inflammation at the earliest stages. The present study aimed to evaluate the molecular profiles of inflamed and unaffected colon mucosa from patients with mild Crohn's disease (CD) and ulcerative colitis (UC), in order to identify a more sensitive method for monitoring mucosal impairment. Patients were recruited and colon biopsies from the inflamed and the normal-appearing mucosa of patients with mild IBD were obtained by colonoscopy. Gene expression analysis was performed using microarrays, after which Gene Ontology and clustering were performed using bioinformatics. In addition, the levels of inflammatory cytokines were analyzed by reverse transcription-quantitative polymerase chain reaction. A total of 620 genes in the inflamed and 210 genes in the unaffected colon mucosa with at least a 3-fold change, as compared with healthy controls, were detected in patients with mild CD, and 339 genes in the inflamed and 483 genes in the unaffected colon mucosa were detected in patients with mild UC. Heat mapping demonstrated a similarity in the gene alteration patterns, and altered transcripts overlapped, between the inflamed and unaffected colon mucosa. Interferon-γ and interleukin-17 mRNA levels were comparably elevated in the inflamed and unaffected colon mucosa from patients with IBD. Marked gene expression alterations were detected in the inflamed and unaffected colon mucosa from patients with mild IBD, and these showed marked similarity and overlap between the two groups. The results of the present study suggested that inflammation was not limited to the endoscopic lesions and that gene expression profiling may be considered a sensitive tool for monitoring mucosal inflammation, predicting relapses and optimizing therapeutic strategies for patients with IBD.

show abstract

Section: Discussionsupporting

confidence: 81%

Gene expression alterations in inflamed and unaffected colon mucosa from patients with mild inflammatory bowel disease

Lian

et al. 2016

Molecular Medicine Reports

View full text Add to dashboard Cite

show abstract

“…A critical function of DUOX2 in the epithelial defense response against the abundant intestinal microbiota would be consistent with the robust upregulation of DUOX2 in conditions frequently associated with dysbiosis, even in the absence of manifest inflammation. For instance, DUOX2 is markedly upregulated in the intestine of patients with irritable bowel syndrome 7 , in the normal appearing proximal small intestine after ileal pouch-anal anastomosis 8 , and in noninflamed ilea of patients with colon-only Crohn’s disease (cCD) 9 . However, whether DUOX2 induction is a consequence of microbial dysbiosis and plays a role in maintaining immune homeostasis is currently unclear.…”

mentioning

confidence: 99%

Increased Expression of DUOX2 Is an Epithelial Response to Mucosal Dysbiosis Required for Immune Homeostasis in Mouse Intestine

et al. 2015

View full text Add to dashboard Cite

BACKGROUND & AIMS Dual oxidase 2 (DUOX2), a hydrogen-peroxide generator at the apical membrane of gastrointestinal epithelia, is upregulated in patients with inflammatory bowel disease (IBD) before the onset of inflammation, but little is known about its effects. We investigated the role of DUOX2 in maintaining mucosal immune homeostasis in mice. METHODS We analyzed the regulation of DUOX2 in intestinal tissues of germ-free vs conventional mice, mice given antibiotics or colonized with only segmented filamentous bacteria, mice associated with human microbiota, and mice with deficiencies in interleukin (IL)23 and 22 signaling. We performed 16S rRNA gene quantitative PCR of intestinal mucosa and mesenteric lymph nodes of Duoxa−/− mice that lack functional DUOX enzymes. Genes differentially expressed in Duoxa−/− mice compared to co-housed wild type littermates were correlated with gene expression changes in early-stage IBD using gene set enrichment analysis. RESULTS Colonization of mice with segmented filamentous bacteria upregulated intestinal expression of DUOX2. DUOX2 regulated redox-signaling within mucosa-associated microbes and restricted bacterial access to lymphatic tissues of the mice, thereby reducing microbiota-induced immune responses. Induction of Duox2 transcription by microbial colonization did not require the mucosal cytokines IL17 or IL22, although IL22 increased expression of Duox2. Dysbiotic, but not healthy human microbiota, activated a DUOX2 response in recipient germ-free mice that corresponded to abnormal colonization of the mucosa with distinct populations of microbes. In Duoxa−/− mice, abnormalities in ileal mucosal gene expression at homeostasis recapitulated those in patients with mucosal dysbiosis. CONCLUSIONS DUOX2 regulates interactions between the intestinal microbiota and the mucosa to maintain immune homeostasis in mice. Mucosal dysbiosis leads to increased expression of DUOX2, which might be a marker of perturbed mucosal homeostasis in patients with early-stage IBD.

show abstract

“…The finding that disease severity prior to surgery is associated with pouch outcome may reflect the fact that pathological changes exist in IBD patients (both CD and UC) even in areas that are grossly normal, and that such changes may be associated with disease severity and not exist among normal controls …”

Section: Discussionmentioning

confidence: 99%

The outcome of ulcerative colitis patients undergoing pouch surgery is determined by pre‐surgical factors

Yanai

Ben‐Shachar

Mlynarsky

et al. 2017

Aliment Pharmacol Ther

View full text Add to dashboard Cite

show abstract

Gene expression alterations in ulcerative colitis patients after restorative proctocolectomy extend to the small bowel proximal to the pouch

Abstract: Significant gene expression alterations exist in an apparently unaffected proximal SB. Alterations in the pouch and the proximal SB were comparable, suggesting that inflammation may not be limited to the pouch, but that it extends to the proximal SB.

Cited by 26 publications

References 28 publications

Gene expression alterations in inflamed and unaffected colon mucosa from patients with mild inflammatory bowel disease

Gene expression alterations in inflamed and unaffected colon mucosa from patients with mild inflammatory bowel disease

Increased Expression of DUOX2 Is an Epithelial Response to Mucosal Dysbiosis Required for Immune Homeostasis in Mouse Intestine

The outcome of ulcerative colitis patients undergoing pouch surgery is determined by pre‐surgical factors

Contact Info

Product

Resources

About