Bacteroides thetaiotaomicron Ameliorates Colon Inflammation in Preclinical Models of Crohn's Disease

Margaret Delday, Imke Mulder (Corresponding Author), Elizabeth T Logan, George Grant

Research output: Contribution to journalArticle

4 Citations (Scopus)
6 Downloads (Pure)

Abstract

Background: Alterations in the gut microbiota are strongly associated with the development of inflammatory bowel disease (IBD), particularly with Crohn's disease, which is characterized by reduced abundance of commensal anaerobic bacteria including members of the Bacteroides genus. Our aim was to investigate the protective effects of Bacteroides thetaiotaomicron, an abundant member of this genus, in different rodent models of IBD.

Methods: We assessed the effect of B. thetaiotaomicron administration on primary readouts of colitis (weight loss, histopathology, and immune parameters) in dextran sodium sulphate (DSS) and interleukin-10 knockout (IL10KO) models of IBD. Efficacy of a freeze-dried bacterial formulation and a purified recombinant protein of B. thetaiotaomicron was also investigated.

Results: B. thetaiotaomicron showed protective effects in both DSS and IL10KO rodent models, as demonstrated by significant amelioration of weight loss, colon shortening, histopathological damage and immune activation. This efficacy was not exclusive to actively growing bacterial preparations but was retained by freeze-dried cells of B. thetaiotaomicron. A pirin-like protein (PLP) of B. thetaiotaomicron, identified by microarray analysis during coculture of the bacterial strain with Caco-2 cells, reduced pro-inflammatory NF-κB signalling in these intestinal epithelial cells. Recombinant PLP partially recapitulated the effect of the whole strain in a rat DSS model.

Conclusions: B. thetaiotaomicron displays strong efficacy in preclinical models of IBD and protects against weight loss, histopathological changes in the colon and inflammatory markers. These data indicate that the live strain or its products may be a novel alternative to current treatment options for Crohn's disease.

Original languageEnglish
Pages (from-to)85-96
Number of pages11
JournalInflammatory Bowel Diseases
Volume25
Issue number1
Early online date12 Sep 2018
DOIs
Publication statusPublished - 1 Jan 2019

Fingerprint

Crohn Disease
Colon
Inflammatory Bowel Diseases
Dextran Sulfate
Inflammation
Weight Loss
Interleukin-10
Rodentia
Bacteroides
Caco-2 Cells
Anaerobic Bacteria
Colitis
Microarray Analysis
Coculture Techniques
Recombinant Proteins
Epithelial Cells
Bacteroides thetaiotaomicron
Proteins
IgA receptor

Keywords

  • bacteroides thetaiotaomicron
  • Crohn’s disease
  • dextran sodium sulphate
  • knockout
  • inflammatory bowel disease
  • Bacteroides thetaiotaomicron
  • Crohn's disease
  • EXTRAINTESTINAL MANIFESTATIONS
  • MANAGEMENT
  • GUT
  • ALPHA
  • BOWEL-DISEASE
  • CHILDREN
  • INTESTINAL INFLAMMATION
  • COLITIS
  • MICE
  • DYSFUNCTION

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

Cite this

Bacteroides thetaiotaomicron Ameliorates Colon Inflammation in Preclinical Models of Crohn's Disease. / Delday, Margaret; Mulder, Imke (Corresponding Author); Logan, Elizabeth T; Grant, George.

In: Inflammatory Bowel Diseases, Vol. 25, No. 1, 01.01.2019, p. 85-96.

Research output: Contribution to journalArticle

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AB - Background: Alterations in the gut microbiota are strongly associated with the development of inflammatory bowel disease (IBD), particularly with Crohn's disease, which is characterized by reduced abundance of commensal anaerobic bacteria including members of the Bacteroides genus. Our aim was to investigate the protective effects of Bacteroides thetaiotaomicron, an abundant member of this genus, in different rodent models of IBD.Methods: We assessed the effect of B. thetaiotaomicron administration on primary readouts of colitis (weight loss, histopathology, and immune parameters) in dextran sodium sulphate (DSS) and interleukin-10 knockout (IL10KO) models of IBD. Efficacy of a freeze-dried bacterial formulation and a purified recombinant protein of B. thetaiotaomicron was also investigated.Results: B. thetaiotaomicron showed protective effects in both DSS and IL10KO rodent models, as demonstrated by significant amelioration of weight loss, colon shortening, histopathological damage and immune activation. This efficacy was not exclusive to actively growing bacterial preparations but was retained by freeze-dried cells of B. thetaiotaomicron. A pirin-like protein (PLP) of B. thetaiotaomicron, identified by microarray analysis during coculture of the bacterial strain with Caco-2 cells, reduced pro-inflammatory NF-κB signalling in these intestinal epithelial cells. Recombinant PLP partially recapitulated the effect of the whole strain in a rat DSS model.Conclusions: B. thetaiotaomicron displays strong efficacy in preclinical models of IBD and protects against weight loss, histopathological changes in the colon and inflammatory markers. These data indicate that the live strain or its products may be a novel alternative to current treatment options for Crohn's disease.

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