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

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 exchang...

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Bibliographic Details
Published in:Mucosal immunology 2018-09, Vol.11 (5), p.1329-1341
Main Authors: 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
Format: Article
Language:English
Subjects:
Animals
Bacteroidaceae - immunology
Colitis
Colitis - metabolism
Colon
Digestive system
Digestive tract
Dysbacteriosis
Dysbiosis - immunology
Dysbiosis - metabolism
Dysbiosis - microbiology
Epithelial Cells - immunology
Epithelial Cells - metabolism
Epithelial Cells - microbiology
Fecal microflora
Female
Firmicutes - immunology
Gastrointestinal Microbiome - immunology
Germ-Free Life
Germfree
Hydrogen
Hydrogen-Ion Concentration
Immune response
Immunity - immunology
Inflammation - immunology
Inflammation - metabolism
Inflammation - microbiology
Inflammatory bowel disease
Inflammatory bowel diseases
Inflammatory Bowel Diseases - immunology
Inflammatory Bowel Diseases - metabolism
Inflammatory Bowel Diseases - microbiology
Interleukin 10
Interleukin-10 - metabolism
Intestinal microflora
Intestinal Mucosa - immunology
Intestinal Mucosa - metabolism
Intestinal Mucosa - microbiology
Intestine
Male
Mice
Mice, Inbred C57BL
Microbiomes
Mucosal immunity
Na+/H+-exchanging ATPase
pH effects
Sodium
Sodium-Hydrogen Exchanger 3 - metabolism
Sodium-Hydrogen Exchangers - metabolism
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Summary: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.
ISSN:1933-0219
1935-3456
DOI:10.1038/s41385-018-0035-2