The microenvironment of injured murine gut elicits a local pro-restitutive microbiota

Ashfaqul Alam, Giovanna Leoni, Miguel Quiros, Huixia Wu, Chirayu Desai, Hikaru Nishio, Rheinallt M. Jones, Asma Nusrat, Andrew S. Neish

Research output: Contribution to journalArticlepeer-review

149 Scopus citations


The mammalian intestine houses a complex microbial community, which influences normal epithelial growth and development, and is integral to the repair of damaged intestinal mucosa1-3. Restitution of injured mucosa involves the recruitment of immune cells, epithelial migration and proliferation4,5. Although microenvironmental alterations have been described in wound healing 6, a role for extrinsic influences, such as members of the microbiota, has not been reported. Here, we show that a distinct subpopulation of the normal mucosal-associated gut microbiota expands and preferentially colonizes sites of damaged murine mucosa in response to local environmental cues. Our results demonstrate that formyl peptide receptor 1 (FPR1) and neutrophilic NADPH oxidase (NOX2) are required for the rapid depletion of microenvironmental oxygen and compensatory responses, resulting in a dramatic enrichment of an anaerobic bacterial consortium. Furthermore, the dominant member of this wound-mucosa-associated microbiota, Akkermansia muciniphila (an anaerobic, mucinophilic gut symbiont7,8), stimulated proliferation and migration of enterocytes adjacent to the colonic wounds in a process involving FPR1 and intestinal epithelial-cell-specific NOX1-dependent redox signalling. These findings thus demonstrate how wound microenvironments induce the rapid emergence of 'probiont' species that contribute to enhanced repair of mucosal wounds. Such microorganisms could be exploited as potential therapeutics.

Original languageEnglish
Article number15021
JournalNature Microbiology
Issue number2
StatePublished - Jan 27 2016

Bibliographical note

Funding Information:
This work was supported by grants RO1DK089763 to A.S.N. and A.N., RO1DK055679 to A.N. and RO1AI64462 to A.S.N. A.A. is supported by a Career Development Award from the Crohn's and Colitis Foundation of America.

Publisher Copyright:
© 2016 Macmillan Publishers Limited. All rights reserved.

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology


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