Microbiome Analysis of Mucosal Ileoanal Pouch in Ulcerative Colitis Patients Revealed Impairment of the Pouches Immunometabolites.

Orazio Palmieri,Giuseppe Corritore,Angelo Andriulli,Stefano Castellana,Fabrizio Bossa,Anna Panza,Maria Guerra,Anna Latiano,Rosanna Fontana,Giuseppina Martino,Francesco Perri,Tommaso Mazza,Giuseppe Biscaglia,Tiziana Latiano

doi:10.3390/cells10113243

Orazio Palmieri, Giuseppe Corritore + Show 12 more

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https://doi.org/10.3390/cells10113243

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Abstract

The pathogenesis of ulcerative colitis (UC) is unknown, although genetic loci and altered gut microbiota have been implicated. Up to a third of patients with moderate to severe UC require proctocolectomy with ileal pouch ano-anastomosis (IPAA). We aimed to explore the mucosal microbiota of UC patients who underwent IPAA. Methods: For microbiome analysis, mucosal specimens were collected from 34 IPAA individuals. Endoscopic and histological examinations of IPAA were normal in 21 cases, while pouchitis was in 13 patients. 19 specimens from the healthy control (10 from colonic and 9 from ileum) were also analyzed. Data were analyzed using an ensemble of software packages: QIIME2, coda-lasso, clr-lasso, PICRUSt2, and ALDEx2. Results: IPAA specimens had significantly lower bacterial diversity as compared to normal. The microbial composition of the normal pouch was also decreased also when compared to pouchitis. Faecalibacterium prausnitzii, Gemmiger formicilis, Blautia obeum, Ruminococcus torques, Dorea formicigenerans, and an unknown species from Roseburia were the most uncommon in pouch/pouchitis, while an unknown species from Enterobacteriaceae was over-represented. Propionibacterium acnes and Enterobacteriaceae were the species most abundant in the pouchitis and in the normal pouch, respectively. Predicted metabolic pathways among the IPAA bacterial communities revealed an important role of immunometabolites such as SCFA, butyrate, and amino acids. Conclusions: Our findings showed specific bacterial signature hallmarks of dysbiosis and could represent bacterial biomarkers in IPAA patients useful to develop novel treatments in the future by modulating the gut microbiota through the administration of probiotic immunometabolites-producing bacterial strains and the addition of specific prebiotics and the faecal microbiota transplantation.

Highlights

Ulcerative colitis (UC) is a chronic inflammatory disease of unknown etiology that affects the colon and rectum
A total of 34 mucosal biopsy specimens were collected from ulcerative colitis (UC) patients with an ileal pouch, 21 of them with normal endoscopy and histology, and 13 with pouchitis
19 specimens pinched from healthy controls (HC) were analyzed; 10 of them with normal colonic mucosa (5 female, mean age at recruitment 47.1 ± 16.2) and 9 with normal ileum (5 female, mean age at recruitment 36.2 ± 14.8)

Summary

Introduction

Ulcerative colitis (UC) is a chronic inflammatory disease of unknown etiology that affects the colon and rectum. The therapeutic approach in UC patients mainly depends on the severity of the disease and the extent of the inflammation. Up to a third of patients with moderate to severe UC still requires colectomy, due to therapy failure or to the development of dysplasia [2]. Up to half of the patients after IPAA develop inflammation of this reservoir, named pouchitis, which represents the most frequent complication [4]. The etiology of pouchitis is not entirely understood, several risk factors have been proposed, such as a previous extensive UC or the presence of backwash ileitis, concomitant primary sclerosing cholangitis, non-steroidal anti-inflammatory drugs use, and positivity for pANCA, ASCA, and Anti-CBir1 [5,6]

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