Microbial symbionts accelerate wound healing via the neuropeptide hormone oxytocin

• Published in: PloS one Vol. 8; no. 10; p. e78898
• Main Authors: Poutahidis, Theofilos, Kearney, Sean M, Levkovich, Tatiana, Qi, Peimin, Varian, Bernard J, Lakritz, Jessica R, Ibrahim, Yassin M, Chatzigiagkos, Antonis, Alm, Eric J, Erdman, Susan E
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30-10-2013; Public Library of Science (PLoS)
• Subjects: Animals; Bacteria; Bioengineering; Biopsy; Brain; Brain injury; Cancer; CD25 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Collagen - metabolism; Cytokines; Diabetes mellitus; DNA-Binding Proteins - deficiency; Drinking water; Drinking Water - microbiology; Female; Fitness; Foxp3 protein; Hypotheses; Immune system; Immunoregulation; Inflammation; Intestinal microflora; Laboratories; Lactic acid; Lactobacillus reuteri; Lactobacillus reuteri - physiology; Lymphocytes T; Metabolism; Metabolites; Mice; Microbiota; Microorganisms; Neuropeptides; Nitric oxide; Oxytocin; Oxytocin - blood; Oxytocin - metabolism; Physical fitness; Probiotics; RAG2 protein; Recovery; Rodents; Skin; Studies; Surgery; Symbionts; Symbiosis; Time Factors; Traditions; Up-Regulation; Vagus nerve; Veterinary medicine; Wound Healing; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0078898

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.