Identification of commensal species positively correlated with early stress responses to a compromised mucus barrier

Bruno Sovran, Peng Lu, Linda M.P. Loonen, Floor Hugenholtz, Clara Belzer, Ellen H. Stolte, Mark V. Boekschoten, Peter Van Baarlen, Hauke Smidt, Michiel Kleerebezem, Paul De Vos, Ingrid B. Renes, Jerry M. Wells*, Jan Dekker

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

Abstract

Background: Our aims were (1) to correlate changes in the microbiota to intestinal gene expression before and during the development of colitis in Muc2 -/- mice and (2) to investigate whether the heterozygote Muc2 +/- mouse would reveal host markers of gut barrier stress. Methods: Colon histology, transcriptomics, and microbiota profiling of faecal samples was performed on wild type, Muc2 +/-, and Muc2 -/- mice at 2, 4, and 8 weeks of age. Results: Muc2 -/- mice develop colitis in proximal colon after weaning, resulting in inflammatory and adaptive immune responses, and expression of genes associated with human inflammatory bowel disease. Muc2 +/- mice do not develop colitis, but produce a thinner mucus layer. The transcriptome of Muc2 +/- mice revealed differential expression of genes participating in mucosal stress responses and exacerbation of a transient inflammatory state around the time of weaning. Young wild type and Muc2 +/- mice have a more constrained group of bacteria as compared with the Muc2 -/- mice, but at 8 weeks the microbiota composition is more similar in all mice. At all ages, microbiota composition discriminated the groups of mice according to their genotype. Specific bacterial clusters correlated with altered gene expression responses to stress and bacteria, before colitis development, including colitogenic members of the genus Bacteroides. Conclusions: The abundance of Bacteroides pathobionts increased before histological signs of pathology suggesting they may play a role in triggering the development of colitis. The Muc2 +/- mouse produces a thinner mucus layer and can be used to study mucus barrier stress in the absence of colitis.

Original languageEnglish
Pages (from-to)826-840
JournalInflammatory Bowel Diseases
Volume22
Issue number4
DOIs
Publication statusPublished - 2016

Fingerprint

Mucus
Colitis
Microbiota
Gene Expression
Bacteroides
Weaning
Colon
Bacteria
Adaptive Immunity
Heterozygote
Inflammatory Bowel Diseases
Transcriptome
Histology
Genotype
Pathology

Keywords

  • Bacteroidetes
  • colitis
  • Muc2 deficiency
  • stress markers

Cite this

@article{2ca84e6093344c7bb9697f1c2f1b0fcb,
title = "Identification of commensal species positively correlated with early stress responses to a compromised mucus barrier",
abstract = "Background: Our aims were (1) to correlate changes in the microbiota to intestinal gene expression before and during the development of colitis in Muc2 -/- mice and (2) to investigate whether the heterozygote Muc2 +/- mouse would reveal host markers of gut barrier stress. Methods: Colon histology, transcriptomics, and microbiota profiling of faecal samples was performed on wild type, Muc2 +/-, and Muc2 -/- mice at 2, 4, and 8 weeks of age. Results: Muc2 -/- mice develop colitis in proximal colon after weaning, resulting in inflammatory and adaptive immune responses, and expression of genes associated with human inflammatory bowel disease. Muc2 +/- mice do not develop colitis, but produce a thinner mucus layer. The transcriptome of Muc2 +/- mice revealed differential expression of genes participating in mucosal stress responses and exacerbation of a transient inflammatory state around the time of weaning. Young wild type and Muc2 +/- mice have a more constrained group of bacteria as compared with the Muc2 -/- mice, but at 8 weeks the microbiota composition is more similar in all mice. At all ages, microbiota composition discriminated the groups of mice according to their genotype. Specific bacterial clusters correlated with altered gene expression responses to stress and bacteria, before colitis development, including colitogenic members of the genus Bacteroides. Conclusions: The abundance of Bacteroides pathobionts increased before histological signs of pathology suggesting they may play a role in triggering the development of colitis. The Muc2 +/- mouse produces a thinner mucus layer and can be used to study mucus barrier stress in the absence of colitis.",
keywords = "Bacteroidetes, colitis, Muc2 deficiency, stress markers",
author = "Bruno Sovran and Peng Lu and Loonen, {Linda M.P.} and Floor Hugenholtz and Clara Belzer and Stolte, {Ellen H.} and Boekschoten, {Mark V.} and {Van Baarlen}, Peter and Hauke Smidt and Michiel Kleerebezem and {De Vos}, Paul and Renes, {Ingrid B.} and Wells, {Jerry M.} and Jan Dekker",
year = "2016",
doi = "10.1097/MIB.0000000000000688",
language = "English",
volume = "22",
pages = "826--840",
journal = "Inflammatory Bowel Diseases",
issn = "1078-0998",
publisher = "Lippincott, Williams & Wilkins",
number = "4",

}

Identification of commensal species positively correlated with early stress responses to a compromised mucus barrier. / Sovran, Bruno; Lu, Peng; Loonen, Linda M.P.; Hugenholtz, Floor; Belzer, Clara; Stolte, Ellen H.; Boekschoten, Mark V.; Van Baarlen, Peter; Smidt, Hauke; Kleerebezem, Michiel; De Vos, Paul; Renes, Ingrid B.; Wells, Jerry M.; Dekker, Jan.

In: Inflammatory Bowel Diseases, Vol. 22, No. 4, 2016, p. 826-840.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Identification of commensal species positively correlated with early stress responses to a compromised mucus barrier

AU - Sovran, Bruno

AU - Lu, Peng

AU - Loonen, Linda M.P.

AU - Hugenholtz, Floor

AU - Belzer, Clara

AU - Stolte, Ellen H.

AU - Boekschoten, Mark V.

AU - Van Baarlen, Peter

AU - Smidt, Hauke

AU - Kleerebezem, Michiel

AU - De Vos, Paul

AU - Renes, Ingrid B.

AU - Wells, Jerry M.

AU - Dekker, Jan

PY - 2016

Y1 - 2016

N2 - Background: Our aims were (1) to correlate changes in the microbiota to intestinal gene expression before and during the development of colitis in Muc2 -/- mice and (2) to investigate whether the heterozygote Muc2 +/- mouse would reveal host markers of gut barrier stress. Methods: Colon histology, transcriptomics, and microbiota profiling of faecal samples was performed on wild type, Muc2 +/-, and Muc2 -/- mice at 2, 4, and 8 weeks of age. Results: Muc2 -/- mice develop colitis in proximal colon after weaning, resulting in inflammatory and adaptive immune responses, and expression of genes associated with human inflammatory bowel disease. Muc2 +/- mice do not develop colitis, but produce a thinner mucus layer. The transcriptome of Muc2 +/- mice revealed differential expression of genes participating in mucosal stress responses and exacerbation of a transient inflammatory state around the time of weaning. Young wild type and Muc2 +/- mice have a more constrained group of bacteria as compared with the Muc2 -/- mice, but at 8 weeks the microbiota composition is more similar in all mice. At all ages, microbiota composition discriminated the groups of mice according to their genotype. Specific bacterial clusters correlated with altered gene expression responses to stress and bacteria, before colitis development, including colitogenic members of the genus Bacteroides. Conclusions: The abundance of Bacteroides pathobionts increased before histological signs of pathology suggesting they may play a role in triggering the development of colitis. The Muc2 +/- mouse produces a thinner mucus layer and can be used to study mucus barrier stress in the absence of colitis.

AB - Background: Our aims were (1) to correlate changes in the microbiota to intestinal gene expression before and during the development of colitis in Muc2 -/- mice and (2) to investigate whether the heterozygote Muc2 +/- mouse would reveal host markers of gut barrier stress. Methods: Colon histology, transcriptomics, and microbiota profiling of faecal samples was performed on wild type, Muc2 +/-, and Muc2 -/- mice at 2, 4, and 8 weeks of age. Results: Muc2 -/- mice develop colitis in proximal colon after weaning, resulting in inflammatory and adaptive immune responses, and expression of genes associated with human inflammatory bowel disease. Muc2 +/- mice do not develop colitis, but produce a thinner mucus layer. The transcriptome of Muc2 +/- mice revealed differential expression of genes participating in mucosal stress responses and exacerbation of a transient inflammatory state around the time of weaning. Young wild type and Muc2 +/- mice have a more constrained group of bacteria as compared with the Muc2 -/- mice, but at 8 weeks the microbiota composition is more similar in all mice. At all ages, microbiota composition discriminated the groups of mice according to their genotype. Specific bacterial clusters correlated with altered gene expression responses to stress and bacteria, before colitis development, including colitogenic members of the genus Bacteroides. Conclusions: The abundance of Bacteroides pathobionts increased before histological signs of pathology suggesting they may play a role in triggering the development of colitis. The Muc2 +/- mouse produces a thinner mucus layer and can be used to study mucus barrier stress in the absence of colitis.

KW - Bacteroidetes

KW - colitis

KW - Muc2 deficiency

KW - stress markers

U2 - 10.1097/MIB.0000000000000688

DO - 10.1097/MIB.0000000000000688

M3 - Article

VL - 22

SP - 826

EP - 840

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

SN - 1078-0998

IS - 4

ER -