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Microbial Symbionts Accelerate Wound Healing via the Neuropeptide Hormone Oxytocin
Open accessAbstract
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.
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“Indeed, administration of L. reuteri, to mice resulted in an increase in the circulation levels and expression of oxytocin, which was associated with an increase in social behavior (Buffington et al., 2016;Poutahidis et al., 2013).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Poutahidis et al., 2013
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“Interestingly, the effects observed above are dependent on vagal signaling, which blunted the effects of Lactobacillus on host plasma and hypothalamic oxytocin [132,133].”
From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [132]
In the citing paper
“We and others have shown that L. reuteri increases oxytocin levels (Buffington et al., 2016; Poutahidis et al., 2013).”
From Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder (2019) · cites this paper as Poutahidis et al., 2013
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“We and others have previously provided correlational evidence that L. reuteri increases oxytocin levels (Buffington et al., 2016; Poutahidis et al., 2013)”
From Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder (2019) · cites this paper as Poutahidis et al., 2013
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Metadata
- Authors
- Poutahidis, T., Kearney, S. M., Levkovich, T., Qi, P., Varian, B. J., Lakritz, J. R., Ibrahim, Y. M., Chatzigiagkos, A., Alm, E. J., & Erdman, S. E.
- Affiliations
- Aristotle University of Thessaloniki (GR)
- Massachusetts Institute of Technology (US)
- Broad Institute (US)
- Corresponding author
- Erdman, Susan E.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-10-30
- Volume
- 8
- Issue
- 10
- Pages
- e78898
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3813596
- OpenAlex
- W2068527256
- Cited by
- 310
- References
- 85
- Citations by year
- 2026: 19 · 2025: 29 · 2024: 33 · 2023: 25 · 2022: 31 · 2021: 32 · 2020: 31 · 2019: 21 · 2018: 22 · 2017: 18 · 2016: 24 · 2015: 10 · 2014: 14 · 2013: 1
- FWCI
- 17.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Cancer Institute (U01CA164337, R01CA108854)
- National Institute of Environmental Health Sciences (P30ES002109)
- Topics
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- wound healing, gut microbiota, Lactobacillus reuteri, oxytocin, vagus nerve, regulatory T cells, gut-brain-immune axis, lactic acid bacteria, drinking water supplementation, microbial symbionts
- MeSH terms
- Animals, Collagen, DNA-Binding Proteins, Female, Oxytocin, Symbiosis, Time Factors, Wound Healing, CD4-Positive T-Lymphocytes, Up-Regulation, Mice, Limosilactobacillus reuteri, Drinking Water
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