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The Microenvironment of Injured Mucosa Stimulates a Local Pro‐restitutive Microbiota
Author(s) -
Alam Ashfaqul,
Leoni Giovanna,
Quiros Miguel,
Jones Rheinallt,
Nusrat Asma,
Neish Andrew
Publication year - 2015
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.29.1_supplement.142.5
Subject(s) - enterocyte , biology , gut flora , intestinal mucosa , microbiology and biotechnology , akkermansia muciniphila , immunology , small intestine , biochemistry , medicine
Restitution of mucosal injury involves induced and coordinated proliferation and migration of intestinal epithelial cells. The commensal microbiota of the intestine is integral to the repair of damaged intestinal mucosa. N‐formyl peptide receptors (FPRs) are widely expressed pattern recognition receptors that specifically respond to host‐derived and microbial peptides in a redox dependent manner. However, little is known about the host‐microbiota crosstalk mediated by FPRs during repair of gut mucosal injuries. We hypothesized that distinct members of the gut microbiota preferentially colonize the restitutive mucosa to promote wound repair processes in a FPR1‐dependent fashion. For this purpose, defined mechanical wounds were inflicted in the mouse distal colon by using an endoscope and forceps. High throughput sequencing of the V4 region of 16s rRNA gene of the bacteria harvested from mucosal wounds revealed a spatiotemporal shift in the composition and diversity of microbiota. We found several FPR1 and NADPH oxidase NOX2‐dependent microenvironmental changes in mucosal wounds, which include rapid induction of a hypoxic microenvironment, and expression of several HIF1a‐regulated genes, including the mucin muc 3. Interestingly, these events were followed by a dramatic enrichment of a distinct commensal species Akkermansia , an anaerobic, mucinophilic bacterium, which stimulates FPR1 on intestinal epithelial cells to generate reactive oxygen species (ROS) via enterocyte NOX1, resulting in enhanced migration & proliferation of enterocytes. These findings identify a novel role of FPR1 to promote microenvironmental changes that enrich a specific mucosa‐associated bacterium to enhance gut mucosal wound restitution.