Microbial symbionts accelerate wound healing via the neuropeptide hormone oxytocin

PLoS ONE

Volumn 8, Issue 10, 2013, Pages

  Poutahidis, Theofilos ^a,b   Kearney, Sean M ^a,c   Levkovich, Tatiana ^a   Qi, Peimin ^a   Varian, Bernard J ^a   Lakritz, Jessica R ^a   Ibrahim, Yassin M ^a   Chatzigiagkos, Antonis ^b   Alm, Eric J ^c,d   Erdman, Susan E ^a  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^b ARISTOTLE UNIVERSITY OF THESSALONIKI   (Greece)

^c Massachusetts Institute of Technology Cambridge   (United States)

^d BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; CD45RB ANTIGEN; DRINKING WATER; INTERLEUKIN 2 RECEPTOR ALPHA; OXYTOCIN; PROBIOTIC AGENT; RAG2 PROTEIN; TRANSCRIPTION FACTOR FOXP3;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DISEASE COURSE; FEMALE; IMMUNOLOGICAL TOLERANCE; INFLAMMATION; INTESTINE FLORA; LACTIC ACID BACTERIUM; LACTOBACILLUS REUTERI; MALE; MICROBIOME; MOUSE; NONHUMAN; OXYTOCIN BLOOD LEVEL; REGULATORY T LYMPHOCYTE; SUPPLEMENTATION; SYMBIONT; VAGUS NERVE; WOUND; WOUND HEALING;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; COLLAGEN; DNA-BINDING PROTEINS; DRINKING WATER; FEMALE; LACTOBACILLUS REUTERI; MICE; OXYTOCIN; SYMBIOSIS; TIME FACTORS; UP-REGULATION; WOUND HEALING;

EID: 84894235009     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0078898     Document Type: Article

References (85)

1. Gordon JI (2012) Honor thy gut symbionts redux. Science 336: 1251-1253.
2. Clemente JC, Ursell LK, Parfrey LW, Knight R (2012) The impact of the gut microbiota on human health: an integrative view. Cell 148: 1258-1270.
3. Shanahan F (2012) The gut microbiota-a clinical perspective on lessons learned. Nat Rev Gastroenterol Hepatol 9: 609-614.
4. Young VB (2012) The intestinal microbiota in health and disease. Curr Opin Gastroenterol 28: 63-69.
5. Rao VP, Poutahidis T, Ge Z, Nambiar PR, Boussahmain C, et al. (2006) Innate immune inflammatory response against enteric bacteria Helicobacter hepaticus induces mammary adenocarcinoma in mice. Cancer Res 66: 7395-7400. (Pubitemid 44289190)
6. Rao VP, Poutahidis T, Fox JG, Erdman SE (2007) Breast cancer: should gastrointestinal bacteria be on our radar screen? Cancer Res 67: 847-850.
7. Scanlan PD, Shanahan F, Clune Y, Collins JK, O'Sullivan GC, et al. (2008) Culture-independent analysis of the gut microbiota in colorectal cancer and polyposis. Environ Microbiol 10: 789-798. (Pubitemid 351160918)
8. Floch MH, Walker WA, Madsen K, Sanders ME, Macfarlane GT, et al. (2011) Recommendations for probiotic use-2011 update. J Clin Gastroenterol 45 Suppl: S168-171.
9. Chow J, Mazmanian SK (2009) Getting the bugs out of the immune system: do bacterial microbiota "fix" intestinal T cell responses? Cell Host Microbe 5: 8-12.
10. Hooper LV, Littman DR, Macpherson AJ (2012) Interactions between the microbiota and the immune system. Science 336: 1268-1273.
11. Chung H, Pamp SJ, Hill JA, Surana NK, Edelman SM, et al. (2012) Gut immune maturation depends on colonization with a host-specific microbiota. Cell 149: 1578-1593.
12. Maynard CL, Elson CO, Hatton RD, Weaver CT (2012) Reciprocal interactions of the intestinal microbiota and immune system. Nature 489: 231-241.
13. Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, et al. (2012) Host-gut microbiota metabolic interactions. Science 336: 1262-1267.
14. Cryan JF, Dinan TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13: 701-712.
15. Foster JA, McVey Neufeld KA (2013) Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci.
16. Levkovich T, Poutahidis T, Smillie C, Varian BJ, Ibrahim YM, et al. (2013) Probiotic bacteria induce a 'glow of health'. PLoS One 8: e53867.
17. Gimpl G, Fahrenholz F (2001) The oxytocin receptor system: structure, function, and regulation. Physiol Rev 81: 629-683. (Pubitemid 32267075)
18. Wismer Fries AB, Ziegler TE, Kurian JR, Jacoris S, Pollak SD (2005) Early experience in humans is associated with changes in neuropeptides critical for regulating social behavior. Proc Natl Acad Sci U S A 102: 17237-17240. (Pubitemid 41692713)
19. Garrison JL, Macosko EZ, Bernstein S, Pokala N, Albrecht DR, et al. (2012) Oxytocin/vasopressin-related peptides have an ancient role in reproductive behavior. Science 338: 540-543.
20. Camerino C (2009) Low sympathetic tone and obese phenotype in oxytocin-deficient mice. Obesity (Silver Spring) 17: 980-984.
21. Ho JM, Blevins JE (2013) Coming full circle: contributions of central and peripheral oxytocin actions to energy balance. Endocrinology 154: 589-596.
22. Maccio A, Madeddu C, Chessa P, Panzone F, Lissoni P, et al. (2010) Oxytocin both increases proliferative response of peripheral blood lymphomonocytes to phytohemagglutinin and reverses immunosuppressive estrogen activity. In Vivo 24: 157-163.
23. Johnson HM, Torres BA (1985) Regulation of lymphokine production by arginine vasopressin and oxytocin: modulation of lymphocyte function by neurohypophyseal hormones. J Immunol 135: 773s-775s. (Pubitemid 16229428)
24. Barnard A, Layton D, Hince M, Sakkal S, Bernard C, et al. (2008) Impact of the neuroendocrine system on thymus and bone marrow function. Neuroimmunomodulation 15: 7-18.
25. Davari S, Talaei SA, Alaei H, Salami M (2013) Probiotics treatment improves diabetes-induced impairment of synaptic activity and cognitive function: Behavioral and electrophysiological proofs for microbiome-gut-brain axis. Neuroscience.
26. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, et al. (2011) Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A 108: 16050-16055.
27. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, et al. (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405: 458-462. (Pubitemid 30367422)
28. Johnston GR, Webster NR (2009) Cytokines and the immunomodulatory function of the vagus nerve. Br J Anaesth 102: 453-462.
29. Dreifuss JJ, Raggenbass M, Charpak S, Dubois-Dauphin M, Tribollet E (1988) A role of central oxytocin in autonomic functions: its action in the motor nucleus of the vagus nerve. Brain Res Bull 20: 765-770. (Pubitemid 19266463)
30. Frank S, Kampfer H (2003) Excisional wound healing. An experimental approach. Methods Mol Med 78: 3-15.
31. Gurtner GC, Werner S, Barrandon Y, Longaker MT (2008) Wound repair and regeneration. Nature 453: 314-321. (Pubitemid 351693137)
32. Martin P (1997) Wound healing-aiming for perfect skin regeneration. Science 276: 75-81.
33. Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315: 1650-1659.
34. Saulnier DM, Santos F, Roos S, Mistretta TA, Spinler JK, et al. (2011) Exploring metabolic pathway reconstruction and genome-wide expression profiling in Lactobacillus reuteri to define functional probiotic features. PLoS One 6: e18783.
35. Gallucci RM, Simeonova PP, Matheson JM, Kommineni C, Guriel JL, et al. (2000) Impaired cutaneous wound healing in interleukin-6-deficient and immunosuppressed mice. Faseb Journal 14: 2525-2531.
36. Swift ME, Kleinman HK, DiPietro LA (1999) Impaired wound repair and delayed angiogenesis in aged mice. Lab Invest 79: 1479-1487. (Pubitemid 30013913)
37. Di Giacinto C, Marinaro M, Sanchez M, Strober W, Boirivant M (2005) Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells. J Immunol 174: 3237-3246. (Pubitemid 40354026)
38. Erdman SE, Fox JG, Sheppard BJ, Feldman D, Horwitz BH (2001) Regulatory T cells prevent non-B non-T colitis. Gastroenterology (Suppl 1): A524.
39. Erdman SE, Poutahidis T, Tomczak M, Rogers AB, Cormier K, et al. (2003) CD4+ CD25+ regulatory T lymphocytes inhibit microbially induced colon cancer in Rag2-deficient mice. Am J Pathol 162: 691-702. (Pubitemid 36267876)
40. Maloy KJ, Salaun L, Cahill R, Dougan G, Saunders NJ, et al. (2003) CD4+CD25+ T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms. J Exp Med 197: 111-119. (Pubitemid 36110262)
41. Poutahidis T, Kleinewietfeld M, Smillie C, Levkovich T, Perrotta A, et al. (2013) Microbial reprogramming inhibits Western diet-associated obesity. PLoS One 10.
42. Powrie F, Maloy KJ (2003) Immunology. Regulating the regulators. Science 299: 1030-1031.
43. Sakaguchi S, Miyara M, Costantino CM, Hafler DA (2010) FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 10: 490-500.
44. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, et al. (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441: 235-238.
45. Round JL, Mazmanian SK (2010) Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci U S A 107: 12204-12209.
46. Lim MM, Young LJ (2006) Neuropeptidergic regulation of affiliative behavior and social bonding in animals. Horm Behav 50: 506-517. (Pubitemid 44307118)
47. Detillion CE, Craft TK, Glasper ER, Prendergast BJ, DeVries AC (2004) Social facilitation of wound healing. Psychoneuroendocrinology 29: 1004-1011. (Pubitemid 38833527)
48. Braiman-Wiksman L, Solomonik I, Spira R, Tennenbaum T (2007) Novel insights into wound healing sequence of events. Toxicol Pathol 35: 767-779. (Pubitemid 47613607)
49. Grose R, Werner S (2004) Wound-healing studies in transgenic and knockout mice. Mol Biotechnol 28: 147-166. (Pubitemid 41490577)
50. Ndiaye K, Poole DH, Pate JL (2008) Expression and regulation of functional oxytocin receptors in bovine T lymphocytes. Biol Reprod 78: 786-793. (Pubitemid 351469342)
51. Costa RA, Ruiz-de-Souza V, Azevedo GM, Jr., Gava E, Kitten GT, et al. (2011) Indirect effects of oral tolerance improve wound healing in skin. Wound Repair Regen 19: 487-497.
52. Singer AJ, Clark RA (1999) Cutaneous wound healing. N Engl J Med 341: 738-746. (Pubitemid 29407375)
53. Nomura T, Sakaguchi S (2007) Foxp3 and Aire in thymus-generated Treg cells: a link in self-tolerance. Nat Immunol 8: 333-334. (Pubitemid 46745405)
54. Hansenne I, Louis C, Martens H, Dorban G, Charlet-Renard C, et al. (2009) Aire and Foxp3 expression in a particular microenvironment for T cell differentiation. Neuroimmunomodulation 16: 35-44.
55. Dvorak AM (1986) Mast-cell degranulation in human hearts. N Engl J Med 315: 969-970.
56. Tkalcevic VI, Cuzic S, Parnham MJ, Pasalic I, Brajsa K (2009) Differential evaluation of excisional non-occluded wound healing in db/db mice. Toxicol Pathol 37: 183-192.
57. Smits HH, Engering A, van der Kleij D, de Jong EC, Schipper K, et al. (2005) Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J Allergy Clin Immunol 115: 1260-1267. (Pubitemid 40824599)
58. Karimi K, Inman MD, Bienenstock J, Forsythe P (2009) Lactobacillus reuteri-induced regulatory T cells protect against an allergic airway response in mice. Am J Respir Crit Care Med 179: 186-193.
59. Liu Y, Fatheree NY, Dingle BM, Tran DQ, Rhoads JM (2013) Lactobacillus reuteri DSM 17938 Changes the Frequency of Foxp3 (+) Regulatory T Cells in the Intestine and Mesenteric Lymph Node in Experimental Necrotizing Enterocolitis. PLoS One 8: e56547.
60. Hofmann U, Beyersdorf N, Weirather J, Podolskaya A, Bauersachs J, et al. (2012) Activation of CD4+ T lymphocytes improves wound healing and survival after experimental myocardial infarction in mice. Circulation 125: 1652-1663.
61. Richards H, Williams A, Jones E, Hindley J, Godkin A, et al. (2010) Novel role of regulatory T cells in limiting early neutrophil responses in skin. Immunology 131: 583-592.
62. Wetzler C, Kampfer H, Stallmeyer B, Pfeilschifter J, Frank S (2000) Large and sustained induction of chemokines during impaired wound healing in the genetically diabetic mouse: prolonged persistence of neutrophils and macrophages during the late phase of repair. J Invest Dermatol 115: 245-253. (Pubitemid 30637194)
63. Gajendrareddy PK, Engeland CG, Junges R, Horan MP, Rojas IG, et al. (2013) MMP-8 overexpression and persistence of neutrophils relate to stress-impaired healing and poor collagen architecture in mice. Brain Behav Immun 28: 44-48.
64. Ansell DM, Kloepper JE, Thomason HA, Paus R, Hardman MJ (2011) Exploring the "hair growth-wound healing connection": anagen phase promotes wound re-epithelialization. J Invest Dermatol 131: 518-528.
65. Aber C, Jimenez J, Kirsner RS (2011) Hair and wound healing: anagen gets an "A". J Invest Dermatol 131: 278.
66. Donaldson ZR, Young LJ (2008) Oxytocin, vasopressin, and the neurogenetics of sociality. Science 322: 900-904.
67. Lee HJ, Macbeth AH, Pagani JH, Young WS, (2009) Oxytocin: the great facilitator of life. Prog Neurobiol 88: 127-151.
68. Meyer-Lindenberg A, Domes G, Kirsch P, Heinrichs M (2011) Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Nat Rev Neurosci 12: 524-538.
69. Tyzio R, Cossart R, Khalilov I, Minlebaev M, Hubner CA, et al. (2006) Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the fetal brain during delivery. Science 314: 1788-1792. (Pubitemid 44969093)
70. Oliveira-Pelegrin GR, Saia RS, Carnio EC, Rocha MJ (2013) Oxytocin affects nitric oxide and cytokine production by sepsis-sensitized macrophages. Neuroimmunomodulation 20: 65-71.
71. Pittman QJ (2011) A neuro-endocrine-immune symphony. J Neuroendocrinol 23: 1296-1297.
72. Lee YK, Mazmanian SK (2010) Has the microbiota played a critical role in the evolution of the adaptive immune system? Science 330: 1768-1773.
73. Williams Z (2012) Inducing tolerance to pregnancy. N Engl J Med 367: 1159-1161.
74. Poutahidis T, Haigis KM, Rao VP, Nambiar PR, Taylor CL, et al. (2007) Rapid reversal of interleukin-6-dependent epithelial invasion in a mouse model of microbially induced colon carcinoma. Carcinogenesis 28: 2614-2623. (Pubitemid 350238965)
75. Erdman SE, Rao VP, Poutahidis T, Rogers AB, Taylor CL, et al. (2009) Nitric oxide and TNF-{alpha} trigger colonic inflammation and carcinogenesis in Helicobacter hepaticus-infected, Rag2-deficient mice. Proc Natl Acad Sci U S A.
76. Erdman SE, Rao VP, Olipitz W, Taylor CL, Jackson EA, et al. (2010) Unifying roles for regulatory T cells and inflammation in cancer. Int J Cancer 126: 1651-1665.
77. Erdman SE, Rao VP, Poutahidis T, Ihrig MM, Ge Z, et al. (2003) CD4(+)CD25(+) regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice. Cancer Res 63: 6042-6050. (Pubitemid 37187508)
78. Belkaid Y, Liesenfeld O, Maizels RM (2010) 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: induction and control of regulatory T cells in the gastrointestinal tract: consequences for local and peripheral immune responses. Clin Exp Immunol 160: 35-41.
79. Skrundz M, Bolten M, Nast I, Hellhammer DH, Meinlschmidt G (2011) Plasma oxytocin concentration during pregnancy is associated with development of postpartum depression. Neuropsychopharmacology 36: 1886-1893.
80. De Dreu CK, Greer LL, Handgraaf MJ, Shalvi S, Van Kleef GA, et al. (2010) The neuropeptide oxytocin regulates parochial altruism in intergroup conflict among humans. Science 328: 1408-1411.
81. Israel S, Lerer E, Shalev I, Uzefovxky F, Riebold M, et al. (2009) The Oxytocin Receptor (OXTR) Contributes to Prosocial Allocations in the Dictator Game and the Social Value Orientations Task. PLoS One 4: e5535.
82. Fish EN (2008) The X-Files in immunity: sex-based differences predispose immune responses. Nat Rev Immunol 8: 737-744.
83. Andari E, Duhamel JR, Zalla T, Herbrecht E, Leboyer M, et al. (2010) Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci U S A 107: 4389-4394.
84. Aleksandra JerCinoviC RK, Student Member, IEEE, Lojze Vodovnik, Fellow IEEE, Aneta Stefanovska M, ZEEE, Peter KroSelj, Rajko Turk, Ivan DZidiC, Helena Benko, and Rajmond Savin (1994) Low Frequency Pulsed Current and Pressure Ulcer Healing. Ieee Transactions on Rehabilitation Engineering 2: 225-233.
85. Cukjati D, Rebersek S, Miklavcic D (2001) A reliable method of determining wound healing rate. Med Biol Eng Comput 39: 263-271. (Pubitemid 32318501)