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


The mammalian intestine houses a complex microbial community, which influences normal epithelial growth and development, and is integral to the repair of damaged intestinal mucosa13. Restitution of injured mucosa involves the recruitment of immune cells, epithelial migration and proliferation4,5. Although microenvironmental alterations have been described in wound healing6, 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.

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Figure 1: Restitutive wound induces spatiotemporal change of wound mucosa-associated microbiota.
Figure 2: FPR1/NOX2 is required for microenvironmental changes in restitutive wounds, which promote anaerobic mucinophilic Akkermansia.
Figure 3: FPR1 is required for enrichment of Akkermansia sp.
Figure 4: Akkermansia muciniphila enhances redox-dependent wound restitution.


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The authors thank F. David, R. Isett, J. Taylor, H. Yi, M. Zwick and C. Kraft for helpful input. 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.

Author information




A.A., A.N. and A.S.N. conceptualized the study, directed the work and wrote the manuscript. A.A., G.L. A.N. and A.S.N. planned and analysed the experiments. R.M.J., A.A., G.L., M.Q., H.W., C.D. and H.N. performed the experiments.

Corresponding authors

Correspondence to Asma Nusrat or Andrew S. Neish.

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The authors declare no competing financial interests.

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Supplementary Information

Supplementary Figures 1-8 and relative abundance of the bacterial genus as determined by HTS. (PDF 1379 kb)

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Alam, A., Leoni, G., Quiros, M. et al. The microenvironment of injured murine gut elicits a local pro-restitutive microbiota. Nat Microbiol 1, 15021 (2016).

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