title: The microenvironment of injured murine gut elicits a local pro-restitutive microbiota.
abstract: The mammalian intestine houses a complex microbial community, which influences normal epithelial growth and development, and is integral to the repair of damaged intestinal mucosa(1-3). Restitution of injured mucosa involves the recruitment of immune cells, epithelial migration and proliferation(4,5). 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 symbiont(7,8)), 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.
authors: Epithelial Pathobiology and Mucosal Inflammation Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors: Ashfaqul
authors: A
authors: Alam
authors: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, 80336 Munich, Germany.
authors: Giovanna
authors: G
authors: Leoni
authors: Department of Pathology, The University of Michigan, Ann Arbor, Michigan 48109, USA.
authors: Miguel
authors: M
authors: Quiros
authors: Epithelial Pathobiology and Mucosal Inflammation Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors: Huixia
authors: H
authors: Wu
authors: Epithelial Pathobiology and Mucosal Inflammation Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors: Chirayu
authors: C
authors: Desai
authors: Department of Pathology, The University of Michigan, Ann Arbor, Michigan 48109, USA.
authors: Hikaru
authors: http://orcid.org/0000-0001-6210-396X
authors: H
authors: Nishio
authors: Epithelial Pathobiology and Mucosal Inflammation Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors: Rheinallt M
authors: RM
authors: Jones
authors: Department of Pathology, The University of Michigan, Ann Arbor, Michigan 48109, USA.
authors: Asma
authors: A
authors: Nusrat
authors: Epithelial Pathobiology and Mucosal Inflammation Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors: Andrew S
authors: AS
authors: Neish
mesh_terms: D000693:Anaerobiosis; D000818:Animals; D001421:Bacteria, Anaerobic / Q000254:growth & development*; D002465:Cell Movement; D049109:Cell Proliferation; D020895:Enterocytes / Q000502:physiology; D000069196:Gastrointestinal Microbiome; D007413:Intestinal Mucosa / Q000293:injuries* / Q000382:microbiology*; D051379:Mice; D000074624:NADPH Oxidase 1 / Q000378:metabolism; D000074662:NADPH Oxidase 2 / Q000378:metabolism; D044042:Receptors, Formyl Peptide / Q000378:metabolism; D014947:Wounds and Injuries / Q000382:microbiology*
chemical_list: C469988:Fpr1 protein, mouse; D044042:Receptors, Formyl Peptide; C488842:Cybb protein, mouse; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; C000614711:NOX1 protein, mouse