Faecalibacterium prausnitzii Strain HTF-F and Its Extracellular Polymeric Matrix Attenuate Clinical Parameters in DSS-Induced Colitis.

Oriana Rossi,Hana Kozakova,Ellen H Stolte,Martin Schwarzer,M Tanweer Khan,Janneke N Samsom,Harry J Flint,Dagmar Srutkova,Jerry M Wells,Sylvia H Duncan,Tomas Hudcovic,Hermie J M Harmsen

doi:10.1371/journal.pone.0123013

Abstract

A decrease in the abundance and biodiversity of intestinal bacteria within the Firmicutes phylum has been associated with inflammatory bowel disease (IBD). In particular, the anti-inflammatory bacterium Faecalibacterium prausnitzii, member of the Firmicutes phylum and one of the most abundant species in healthy human colon, is underrepresented in the microbiota of IBD patients. The aim of this study was to investigate the immunomodulatory properties of F. prausnitzii strain A2-165, the biofilm forming strain HTF-F and the extracellular polymeric matrix (EPM) isolated from strain HTF-F. For this purpose, the immunomodulatory properties of the F. prausnitzii strains and the EPM were studied in vitro using human monocyte-derived dendritic cells. Then, the capacity of the F. prausnitzii strains and the EPM of HTF-F to suppress inflammation was assessed in vivo in the mouse dextran sodium sulphate (DSS) colitis model. The F. prausnitzii strains and the EPM had anti-inflammatory effects on the clinical parameters measured in the DSS model but with different efficacy. The immunomodulatory effects of the EPM were mediated through the TLR2-dependent modulation of IL-12 and IL-10 cytokine production in antigen presenting cells, suggesting that it contributes to the anti-inflammatory potency of F. prausnitzii HTF-F. The results show that F. prausnitzii HTF-F and its EPM may have a therapeutic use in IBD.

Highlights

Ulcerative colitis (UC) and Crohn’s disease (CD), two forms of inflammatory bowel disease (IBD), are driven by an aberrant inflammatory T cell response to intestinal microbiota in a genetically susceptible host
We demonstrated that F. prausnitzii strain A2-165, the biofilm forming strain HTF-F as well as the extracellular polymeric matrix (EPM) isolated from strain HTF-F can attenuate the clinical symptoms of dextran sodium sulphate (DSS)-induced colitis
In the study of Sokol et al, the colons of mice treated with either F. prausnitzii A2-165 or its supernatant had a reduced amount of IL-12p70 and an elevated amount of IL-10 compared with the colitis control group

Summary

Introduction

Ulcerative colitis (UC) and Crohn’s disease (CD), two forms of inflammatory bowel disease (IBD), are driven by an aberrant inflammatory T cell response to intestinal microbiota in a genetically susceptible host. Treatment of Caco cells with F. prausnitzii culture supernatant was reported to reduce IL-1β-induced NF-κB activation and secretion of IL-8. This was attributed to an as yet unidentified factor secreted in the culture medium as it was not observed using 40 mM butyrate, UV-Killed bacteria or bacterial DNA, membranes and cytoplasmic extract [7]. Administration of F. prausnitzii strain A2-165 and its culture supernatant have been shown to protect against 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in mice [7]. This model is thought to resemble CD because the resulting mucosal inflammation is mediated by a T helper 1 (Th1) response with excessive production of IFN-γ, TNF-α and IL-12. Intragastric administration of F. prausnitzii A2-165 and its culture supernatant have a protective effect against dinitrobenzenesulfonic (DNBS)-induced chronic colitis [6]

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