Intestinal Microbiota Signatures Associated with Inflammation History in Mice Experiencing Recurring Colitis.

David Berry,Eva Hainzl,Christa Schleper,Alexander Loy,Lukas Kenner,Mathias Müller,Thomas Decker,Birgit Strobl,Orest Kuzyk,Tim Urich,Isabella Rauch,Susanne Heider,Clarissa Schwab,Michael Wagner

doi:10.3389/fmicb.2015.01408

Abstract

Acute colitis causes alterations in the intestinal microbiota, but the microbiota is thought to recover after such events. Extreme microbiota alterations are characteristic of human chronic inflammatory bowel diseases, although alterations reported in different studies are divergent and sometimes even contradictory. To better understand the impact of periodic disturbances on the intestinal microbiota and its compositional difference between acute and relapsing colitis, we investigated the beginnings of recurrent inflammation using the dextran sodium sulfate (DSS) mouse model of chemically induced colitis. Using bacterial 16S rRNA gene-targeted pyrosequencing as well as quantitative fluorescence in situ hybridization, we profiled the intestinal and stool microbiota of mice over the course of three rounds of DSS-induced colitis and recovery. We found that characteristic inflammation-associated microbiota could be detected in recovery-phase mice. Successive inflammation episodes further drove the microbiota into an increasingly altered composition post-inflammation, and signatures of colitis history were detectable in the microbiota more sensitively than by pathology analysis. Bacterial indicators of murine colitis history were identified in intestinal and stool samples, with a high degree of consistency between both sample types. Stool may therefore be a promising non-invasive source of bacterial biomarkers that are highly sensitive to inflammation state and history.

Highlights

The intestinal microbiota is increasingly acknowledged to play an important role in health and disease (Clemente et al, 2012; Flint et al, 2012; Tremaroli and Backhed, 2012; Cotillard et al, 2013)
In the present study, using intestinal flush and stool samplings, we have characterized the response of the intestinal microbiota to repeated acute colitis episodes
Using longitudinal fecal sampling of animals, we found that the microbiota of mice with a history of colitis was destabilized and exhibited a directional trajectory increasingly diverging away from the microbiota prior to treatment

Summary

Introduction

The intestinal microbiota is increasingly acknowledged to play an important role in health and disease (Clemente et al, 2012; Flint et al, 2012; Tremaroli and Backhed, 2012; Cotillard et al, 2013). 2012; Faith et al, 2013; David et al, 2014a). Shifts in diet can produce rapid and pronounced alterations in the microbiota (David et al, 2014a,b). Stressors such as antibiotic treatment, enteric infection, and colitis can induce remodeling of the gut microbiota (Garrett et al, 2007; Stecher et al, 2010; Dethlefsen and Relman, 2011; Lepage et al, 2011)

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Results

Conclusion