Microbial dysbiosis associated with impaired intestinal Na+/H+ exchange accelerates and exacerbates colitis in ex-germ free mice

Christy A. Harrison, Daniel Laubitz, Christina L. Ohland, Monica T. Midura-Kiela, Karuna Patil, David G. Besselsen, Deepa R. Jamwal, Christian Jobin, Fayez K Ghishan, Pawel R Kiela

Research output: Contribution to journalArticle

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Abstract

Intestinal epithelial Na+/H+ exchange facilitated by the apical NHE3 (Slc9a3) is a highly regulated process inhibited by intestinal pathogens and in inflammatory bowel diseases. NHE3−/− mice develop spontaneous, bacterially mediated colitis, and IBD-like dysbiosis. Disruption of epithelial Na+/H+ exchange in IBD may thus represent a host response contributing to the altered gut microbial ecology, and may play a pivotal role in modulating the severity of inflammation in a microbiome-dependent manner. To test whether microbiome fostered in an NHE3-deficient environment is able to drive mucosal immune responses affecting the onset or severity of colitis, we performed a series of cohousing experiments and fecal microbiome transplants into germ-free Rag-deficient or IL-10−/− mice. We determined that in the settings where the microbiome of NHE3-deficient mice was stably engrafted in the recipient host, it was able accelerate the onset and amplify severity of experimental colitis. NHE3-deficiency was characterized by the reduction in pH-sensitive butyrate-producing Firmicutes families Lachnospiraceae and Ruminococcaceae (Clostridia clusters IV and XIVa), with an expansion of inflammation-associated Bacteroidaceae. We conclude that the microbiome fostered by impaired epithelial Na+/H+ exchange enhances the onset and severity of colitis through disruption of the gut microbial ecology.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalMucosal Immunology
DOIs
StateAccepted/In press - Jun 6 2018
Externally publishedYes

Fingerprint

Dysbiosis
Microbiota
Colitis
Ecology
Bacteroidaceae
Inflammation
Mucosal Immunity
Clostridium
Butyrates
Inflammatory Bowel Diseases
Interleukin-10

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Microbial dysbiosis associated with impaired intestinal Na+/H+ exchange accelerates and exacerbates colitis in ex-germ free mice. / Harrison, Christy A.; Laubitz, Daniel; Ohland, Christina L.; Midura-Kiela, Monica T.; Patil, Karuna; Besselsen, David G.; Jamwal, Deepa R.; Jobin, Christian; Ghishan, Fayez K; Kiela, Pawel R.

In: Mucosal Immunology, 06.06.2018, p. 1-13.

Research output: Contribution to journalArticle

Harrison, Christy A. ; Laubitz, Daniel ; Ohland, Christina L. ; Midura-Kiela, Monica T. ; Patil, Karuna ; Besselsen, David G. ; Jamwal, Deepa R. ; Jobin, Christian ; Ghishan, Fayez K ; Kiela, Pawel R. / Microbial dysbiosis associated with impaired intestinal Na+/H+ exchange accelerates and exacerbates colitis in ex-germ free mice. In: Mucosal Immunology. 2018 ; pp. 1-13.
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