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.
Highlights
The great importance of gut microbiota in mammalian host health is only recently being recognized in full [1,2,3,4]
This assay applies a standardized 2.0 millimeter full thickness excision of dorsal skin [35]. Using this approach and microscopically examining the excision site of these mice at three, six and twelve days after biopsy (Figures 1a and 1b), we found that aged mice of either gender consuming L. reuteri exhibited proper injury repair in half the time needed for control mice drinking regular water (Figs. 1c and 1d, and Fig. 2a)
We discovered that animals consuming purified lactic acid bacteria from human milk healed their wounds more than twice as fast as control animals
Summary
The great importance of gut microbiota in mammalian host health is only recently being recognized in full [1,2,3,4]. The mechanisms by which gut microbiota impart effects that expand beyond the gastrointestinal tract and become systemic are largely elusive. During a recent study we observed that female mice fed with the lactic acid bacterium Lactobacillus reuteri (L. reuteri) show more frequent grooming activity compared to their control counterparts [16]. This aspect of maternal behavior is regulated at large by the neurohypophyseal hormone oxytocin, best known for its role in parturition and lactation. Our understanding of oxytocin’s classical role, has greatly expanded over the last decades to include substantial central nervous system effects on behavior [17,18,19]. Its most recently discovered but not as wellcharacterized roles include interactions with body energy balance [20,21] and the immune system [22,23,24]
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