Endospore forming bacteria may be associated with maintenance of surgically-induced remission in Crohn\u2019s disease

Michael R Laffin,Heekuk Park,Levinus A Dieleman,Richard N Fedorak,Troy Perry,Masoumeh Sikaroodi,Patrick Gillevet,Karen L Madsen,Bryan Dicken,Karen Kroeker,Gilaad G Kaplan

doi:10.1038/s41598-018-28071-z

Michael R Laffin, Heekuk Park + Show 9 more

Open Access

https://doi.org/10.1038/s41598-018-28071-z

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Abstract

Crohn’s disease (CD) patients who undergo ileocolonic resection (ICR) typically have disease recurrence at the anastomosis which has been linked with a gut dysbiosis. The aims of this study were to define the mucosa-associated microbiota at the time of ICR and to determine if microbial community structure at the time of surgery was predictive of future disease relapse. Ileal biopsies were obtained at surgery and after 6 months from CD subjects undergoing ICR. Composition and function of mucosal-associated microbiota was assessed by 16S rRNA sequencing and PICRUSt analysis. Endoscopic recurrence was assessed using the Rutgeerts score. Analysis of mucosal biopsies taken at the time of surgery showed that decreased Clostridiales together with increased Enterobacteriales predicted disease recurrence. An increase in the endospore-forming Lachnospiraceae from surgery to 6 months post-ICR was associated with remission. A ratio of 3:1 between anaerobic endospore-forming bacterial families and aerobic families within the Firmicutes phylum was predictive of maintenance of remission. Gut recolonization following ICR is facilitated by microbes which are capable of either aerobic respiration or endospore formation. The relative proportions of these species at the time of surgery may be predictive of subsequent microbial community restoration and disease recurrence.

Highlights

Crohn’s disease (CD) involves transmural inflammation of the alimentary tract with ~50% of patients requiring an intestinal resection within 10 years of diagnosis[1,2,3]
We report an association between mucosal-associated microbiota at the time of surgery and post-operative recurrence of CD in a large cohort of post-operative CD patients
We identify a potential impact of endospore-forming bacteria in the process of gut recolonization and post-operative CD recurrence

Summary

Introduction

Crohn’s disease (CD) involves transmural inflammation of the alimentary tract with ~50% of patients requiring an intestinal resection within 10 years of diagnosis[1,2,3]. Intestinal resection constitutes a large insult to the resident microbiota and re-colonization depends upon which commensal organisms are able to survive and reproduce following surgery. In murine models of ICR, Firmicutes dominate post-operatively[12,13]. This is not surprising given the phenotypic diversity of this phylum with aerobes, facultative and strict anaerobes, and species capable of forming endospores. The aims were to define the mucosa-associated microbiota at the time of ICR and at 6 months following ICR, and to determine if the bacterial community structure at the time of surgery was predictive of future disease www.nature.com/scientificreports/. We show that the balance at the time of surgery between groups of bacteria in the Firmicutes phyla capable of either aerobic respiration or endospore formation was predictive of future disease relapse

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