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NHE3 and Clostridium difficile infection (897.5)
Author(s) -
Engevik Melinda,
Yacyshyn Mary,
Yacyshyn Bruce,
Haslam David,
Shull Gary,
Worrell Roger
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.897.5
Subject(s) - microbiology and biotechnology , clostridium difficile , diarrhea , gut flora , clostridium difficile toxin b , clostridium difficile toxin a , biology , antibiotics , medicine , immunology
Although changes in the intestinal microbiota have been linked to diabetes, obesity, Inflammatory Bowel Disease, and Clostridium difficile ‐associated disease, it remains unclear how the intestinal environment, set by ion transport, affects luminal and mucosa‐associated bacterial composition. NHE3 plays an integral role in intestinal Na + absorption, as indicated by chronic diarrhea in NHE3 ‐/‐ mice. In a renal cell lines C. difficile toxin B causes internalization of NHE3. We hypothesize that inhibition of NHE3, by genetic knockout or C. difficile toxin, promotes the proliferation of bacteria capable of growing in a high Na + , alkaline pH environment, altering the gut microbiota composition, which may enhance the C. difficile niche. qPCR was performed on 16S DNA extracted from NHE3 ‐/‐ mouse intestine and human CDI stool. Flame photometry, chloridometry and pH probe was used to measure ion composition and pH. Immunohistochemistry was used to analyze NHE3 localization and mucus oligosaccharide composition. Similar to distal colon samples from NHE3 ‐/‐ mice, fecal samples from humans with C. difficile infection was associated with decreased Firmicutes and increased Bacteroidetes. Fecal [Na + ] was also similarly elevated being consistent with NHE3 inhibition in human CDI . Indeed, NHE3 appeared to be down regulated in biopsy’s from C. difficile infected patients, which likely contributes significantly to diarrhea. These changes also correlated with changes in host mucus oligosaccharide composition. Together these data demonstrate that loss of functional NHE3 occurs in CDI and the resulting alteration in the intestinal environment, may contribute to region‐specific changes in bacteria which serve to favor C. difficile niche development and maintenance. Grant Funding Source : Supported by NIH DK079979 to RTW