Matrix metalloproteinase 9 contributes to gut microbe homeostasis in a model of infectious colitis

David M. Rodrigues, Andrew J. Sousa, Steve P. Hawley, Linda Vong, Melanie Gareau, Sachin A. Kumar, Kathene C. Johnson-Henry, Philip M. Sherman

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Inflammatory bowel diseases are associated with increased expression of zinc-dependent Matrix Metalloproteinase 9 (MMP-9). A stark dysregulation of intestinal mucosal homeostasis has been observed in patients with chronic inflammatory bowel diseases. We therefore sought to determine the contribution of MMP-9 to the pathogenesis of Citrobacter rodentium-induced colitis and its effects on gut microbiome homeostasis. Results: Wild-type and MMP-9/ mice aged 5-6weeks were challenged with C. rodentium by orogastric gavage and sacrificed either 10 or 30days post-infection. Disease severity was assessed by histological analysis of colonic epithelial hyperplasia and by using an in vivo intestinal permeability assay. Changes in the inflammatory responses were measured by using qPCR, and the composition of the fecal microbiome evaluated with both qPCR and terminal restriction fragment length polymorphism. Activation and localization of MMP-9 to the apical surface of the colonic epithelium in response to C. rodentium infection was demonstrated by both zymography and immunocytochemistry. The pro-inflammatory response to infection, including colonic epithelial cell hyperplasia and barrier dysfunction, was similar, irrespective of genotype. Nonmetric multidimensional scaling of terminal restriction fragments revealed a different fecal microbiome composition and C. rodentium colonization pattern between genotypes, with MMP-9/ having elevated levels of protective segmented filamentous bacteria and interleukin-17, and lower levels of C. rodentium. MMP-9/ but not wild-type mice were also protected from reductions in fecal microbial diversity in response to the bacterial enteric infection. Conclusions: These results demonstrate that MMP-9 expression in the colon causes alterations in the fecal microbiome and has an impact on the pathogenesis of bacterial-induced colitis in mice.

Original languageEnglish (US)
Article number105
JournalBMC Microbiology
Volume12
DOIs
StatePublished - 2012
Externally publishedYes

Fingerprint

Citrobacter rodentium
Matrix Metalloproteinase 9
Colitis
Homeostasis
Microbiota
Inflammatory Bowel Diseases
Hyperplasia
Infection
Genotype
Interleukin-17
Bacterial Infections
Restriction Fragment Length Polymorphisms
Zinc
Permeability
Colon
Epithelium
Epithelial Cells
Immunohistochemistry
Bacteria

ASJC Scopus subject areas

  • Microbiology (medical)
  • Microbiology

Cite this

Rodrigues, D. M., Sousa, A. J., Hawley, S. P., Vong, L., Gareau, M., Kumar, S. A., ... Sherman, P. M. (2012). Matrix metalloproteinase 9 contributes to gut microbe homeostasis in a model of infectious colitis. BMC Microbiology, 12, [105]. https://doi.org/10.1186/1471-2180-12-105

Matrix metalloproteinase 9 contributes to gut microbe homeostasis in a model of infectious colitis. / Rodrigues, David M.; Sousa, Andrew J.; Hawley, Steve P.; Vong, Linda; Gareau, Melanie; Kumar, Sachin A.; Johnson-Henry, Kathene C.; Sherman, Philip M.

In: BMC Microbiology, Vol. 12, 105, 2012.

Research output: Contribution to journalArticle

Rodrigues, DM, Sousa, AJ, Hawley, SP, Vong, L, Gareau, M, Kumar, SA, Johnson-Henry, KC & Sherman, PM 2012, 'Matrix metalloproteinase 9 contributes to gut microbe homeostasis in a model of infectious colitis', BMC Microbiology, vol. 12, 105. https://doi.org/10.1186/1471-2180-12-105
Rodrigues, David M. ; Sousa, Andrew J. ; Hawley, Steve P. ; Vong, Linda ; Gareau, Melanie ; Kumar, Sachin A. ; Johnson-Henry, Kathene C. ; Sherman, Philip M. / Matrix metalloproteinase 9 contributes to gut microbe homeostasis in a model of infectious colitis. In: BMC Microbiology. 2012 ; Vol. 12.
@article{663838447e654065af5a9d539f47c6a9,
title = "Matrix metalloproteinase 9 contributes to gut microbe homeostasis in a model of infectious colitis",
abstract = "Background: Inflammatory bowel diseases are associated with increased expression of zinc-dependent Matrix Metalloproteinase 9 (MMP-9). A stark dysregulation of intestinal mucosal homeostasis has been observed in patients with chronic inflammatory bowel diseases. We therefore sought to determine the contribution of MMP-9 to the pathogenesis of Citrobacter rodentium-induced colitis and its effects on gut microbiome homeostasis. Results: Wild-type and MMP-9/ mice aged 5-6weeks were challenged with C. rodentium by orogastric gavage and sacrificed either 10 or 30days post-infection. Disease severity was assessed by histological analysis of colonic epithelial hyperplasia and by using an in vivo intestinal permeability assay. Changes in the inflammatory responses were measured by using qPCR, and the composition of the fecal microbiome evaluated with both qPCR and terminal restriction fragment length polymorphism. Activation and localization of MMP-9 to the apical surface of the colonic epithelium in response to C. rodentium infection was demonstrated by both zymography and immunocytochemistry. The pro-inflammatory response to infection, including colonic epithelial cell hyperplasia and barrier dysfunction, was similar, irrespective of genotype. Nonmetric multidimensional scaling of terminal restriction fragments revealed a different fecal microbiome composition and C. rodentium colonization pattern between genotypes, with MMP-9/ having elevated levels of protective segmented filamentous bacteria and interleukin-17, and lower levels of C. rodentium. MMP-9/ but not wild-type mice were also protected from reductions in fecal microbial diversity in response to the bacterial enteric infection. Conclusions: These results demonstrate that MMP-9 expression in the colon causes alterations in the fecal microbiome and has an impact on the pathogenesis of bacterial-induced colitis in mice.",
author = "Rodrigues, {David M.} and Sousa, {Andrew J.} and Hawley, {Steve P.} and Linda Vong and Melanie Gareau and Kumar, {Sachin A.} and Johnson-Henry, {Kathene C.} and Sherman, {Philip M.}",
year = "2012",
doi = "10.1186/1471-2180-12-105",
language = "English (US)",
volume = "12",
journal = "BMC Microbiology",
issn = "1471-2180",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Matrix metalloproteinase 9 contributes to gut microbe homeostasis in a model of infectious colitis

AU - Rodrigues, David M.

AU - Sousa, Andrew J.

AU - Hawley, Steve P.

AU - Vong, Linda

AU - Gareau, Melanie

AU - Kumar, Sachin A.

AU - Johnson-Henry, Kathene C.

AU - Sherman, Philip M.

PY - 2012

Y1 - 2012

N2 - Background: Inflammatory bowel diseases are associated with increased expression of zinc-dependent Matrix Metalloproteinase 9 (MMP-9). A stark dysregulation of intestinal mucosal homeostasis has been observed in patients with chronic inflammatory bowel diseases. We therefore sought to determine the contribution of MMP-9 to the pathogenesis of Citrobacter rodentium-induced colitis and its effects on gut microbiome homeostasis. Results: Wild-type and MMP-9/ mice aged 5-6weeks were challenged with C. rodentium by orogastric gavage and sacrificed either 10 or 30days post-infection. Disease severity was assessed by histological analysis of colonic epithelial hyperplasia and by using an in vivo intestinal permeability assay. Changes in the inflammatory responses were measured by using qPCR, and the composition of the fecal microbiome evaluated with both qPCR and terminal restriction fragment length polymorphism. Activation and localization of MMP-9 to the apical surface of the colonic epithelium in response to C. rodentium infection was demonstrated by both zymography and immunocytochemistry. The pro-inflammatory response to infection, including colonic epithelial cell hyperplasia and barrier dysfunction, was similar, irrespective of genotype. Nonmetric multidimensional scaling of terminal restriction fragments revealed a different fecal microbiome composition and C. rodentium colonization pattern between genotypes, with MMP-9/ having elevated levels of protective segmented filamentous bacteria and interleukin-17, and lower levels of C. rodentium. MMP-9/ but not wild-type mice were also protected from reductions in fecal microbial diversity in response to the bacterial enteric infection. Conclusions: These results demonstrate that MMP-9 expression in the colon causes alterations in the fecal microbiome and has an impact on the pathogenesis of bacterial-induced colitis in mice.

AB - Background: Inflammatory bowel diseases are associated with increased expression of zinc-dependent Matrix Metalloproteinase 9 (MMP-9). A stark dysregulation of intestinal mucosal homeostasis has been observed in patients with chronic inflammatory bowel diseases. We therefore sought to determine the contribution of MMP-9 to the pathogenesis of Citrobacter rodentium-induced colitis and its effects on gut microbiome homeostasis. Results: Wild-type and MMP-9/ mice aged 5-6weeks were challenged with C. rodentium by orogastric gavage and sacrificed either 10 or 30days post-infection. Disease severity was assessed by histological analysis of colonic epithelial hyperplasia and by using an in vivo intestinal permeability assay. Changes in the inflammatory responses were measured by using qPCR, and the composition of the fecal microbiome evaluated with both qPCR and terminal restriction fragment length polymorphism. Activation and localization of MMP-9 to the apical surface of the colonic epithelium in response to C. rodentium infection was demonstrated by both zymography and immunocytochemistry. The pro-inflammatory response to infection, including colonic epithelial cell hyperplasia and barrier dysfunction, was similar, irrespective of genotype. Nonmetric multidimensional scaling of terminal restriction fragments revealed a different fecal microbiome composition and C. rodentium colonization pattern between genotypes, with MMP-9/ having elevated levels of protective segmented filamentous bacteria and interleukin-17, and lower levels of C. rodentium. MMP-9/ but not wild-type mice were also protected from reductions in fecal microbial diversity in response to the bacterial enteric infection. Conclusions: These results demonstrate that MMP-9 expression in the colon causes alterations in the fecal microbiome and has an impact on the pathogenesis of bacterial-induced colitis in mice.

UR - http://www.scopus.com/inward/record.url?scp=84862174528&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862174528&partnerID=8YFLogxK

U2 - 10.1186/1471-2180-12-105

DO - 10.1186/1471-2180-12-105

M3 - Article

C2 - 22694805

AN - SCOPUS:84862174528

VL - 12

JO - BMC Microbiology

JF - BMC Microbiology

SN - 1471-2180

M1 - 105

ER -