title: Microbial symbionts accelerate wound healing via the neuropeptide hormone oxytocin.
abstract: Wound healing capability is inextricably linked with diverse aspects of physical fitness ranging from recovery after minor injuries and surgery to diabetes and some types of cancer. Impact of the microbiome upon the mammalian wound healing process is poorly understood. We discover that supplementing the gut microbiome with lactic acid microbes in drinking water accelerates the wound-healing process to occur in half the time required for matched control animals. Further, we find that Lactobacillus reuteri enhances wound-healing properties through up-regulation of the neuropeptide hormone oxytocin, a factor integral in social bonding and reproduction, by a vagus nerve-mediated pathway. Bacteria-triggered oxytocin serves to activate host CD4+Foxp3+CD25+ immune T regulatory cells conveying transplantable wound healing capacity to naive Rag2-deficient animals. This study determined oxytocin to be a novel component of a multi-directional gut microbe-brain-immune axis, with wound-healing capability as a previously unrecognized output of this axis. We also provide experimental evidence to support long-standing medical traditions associating diet, social practices, and the immune system with efficient recovery after injury, sustained good health, and longevity.
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America ; Laboratory of Pathology - Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Theofilos
authors.initials: T
authors.lastname: Poutahidis
authors.forename: Sean M
authors.initials: SM
authors.lastname: Kearney
authors.forename: Tatiana
authors.initials: T
authors.lastname: Levkovich
authors.forename: Peimin
authors.initials: P
authors.lastname: Qi
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Varian
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Lakritz
authors.forename: Yassin M
authors.initials: YM
authors.lastname: Ibrahim
authors.forename: Antonis
authors.initials: A
authors.lastname: Chatzigiagkos
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Alm
authors.forename: Susan E
authors.initials: SE
authors.lastname: Erdman
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003094:Collagen / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency; D060766:Drinking Water / Q000382:microbiology; D005260:Female; D052200:Limosilactobacillus reuteri / Q000502:physiology*; D051379:Mice; D010121:Oxytocin / Q000097:blood / Q000378:metabolism*; D013559:Symbiosis; D013997:Time Factors; D015854:Up-Regulation; D014945:Wound Healing
chemical_list: D004268:DNA-Binding Proteins; D060766:Drinking Water; C499308:Rag2 protein, mouse; D010121:Oxytocin; D003094:Collagen