Gut microbiota modulate host immune cells in cancer development and growth

Free Radical Biology and Medicine

Volumn 105, Issue , 2017, Pages 28-34

  Erdman, Susan E ^a   Poutahidis, Theofilos ^a,b  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^b ARISTOTLE UNIVERSITY OF THESSALONIKI   (Greece)

Author keywords

Bacteria; Health; Homeostasis; Hygiene; Lymphocyte; Neutrophil; Thymus

Indexed keywords

CYTOKINE; INTERLEUKIN 10;

ANTIGEN PRESENTING CELL; BACTERIUM; CANCER GROWTH; CANCER IMMUNOTHERAPY; CANCER RISK; CARCINOGENESIS; CD4+ T LYMPHOCYTE; CYTOKINE RELEASE; DIETARY INTAKE; HOMEOSTASIS; HUMAN; HYGIENE HYPOTHESIS; IMMUNOCOMPETENT CELL; IMMUNOLOGICAL TOLERANCE; IMMUNOPATHOGENESIS; INFLAMMATION; INNATE IMMUNITY; INTESTINE FLORA; MUCOSAL IMMUNITY; MYELOID-DERIVED SUPPRESSOR CELL; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; TUMOR ASSOCIATED LEUKOCYTE; ANIMAL; IMMUNOLOGY; MICROBIOLOGY; NEOPLASM; PATHOLOGY; PROTECTION;

ANIMALS; CARCINOGENESIS; CD4-POSITIVE T-LYMPHOCYTES; GASTROINTESTINAL MICROBIOME; HOMEOSTASIS; HUMANS; IMMUNITY, INNATE; NEOPLASMS; PROTECTIVE FACTORS;

EID: 85006790130     PISSN: 08915849     EISSN: 18734596     Source Type: Journal    
DOI: 10.1016/j.freeradbiomed.2016.11.013     Document Type: Review

References (114)

1. [1] Erdman, S.E., Gut microbiota: microbes offer engineering strategies to combat cancer. Nat. Rev. Gastroenterol. Hepatol. 13 (2016), 125–126.
2. [2] Maynard, C.L., Elson, C.O., Hatton, R.D., Weaver, C.T., Reciprocal interactions of the intestinal microbiota and immune system. Nature 489 (2012), 231–241.
3. [3] Troy, E.B., Kasper, D.L., Beneficial effects of Bacteroides fragilis polysaccharides on the immune system. Front. Biosci. (Landmark Ed.) 15 (2010), 25–34.
4. [4] Chinen, T., Rudensky, A.Y., The effects of commensal microbiota on immune cell subsets and inflammatory responses. Immunol. Rev. 245 (2012), 45–55.
5. [5] Blumberg, R., Powrie, F., Microbiota, disease, and back to health: a metastable journey. (137rv137) Sci. Transl. Med., 4, 2012 (137rv137).
6. [6] Erdman, S.E., Poutahidis, T., Gut bacteria and cancer. Biochim. Biophys. Acta 1856 (2015), 86–90.
7. [7] Erdman, S.E., Rao, V.P., Olipitz, W., Taylor, C.L., Jackson, E.A., Levkovich, T., Lee, C.W., Horwitz, B.H., Fox, J.G., Ge, Z., Poutahidis, T., Unifying roles for regulatory T cells and inflammation in cancer. Int J. Cancer 126 (2010), 1651–1665.
8. [8] Rao, V.P., Poutahidis, T., Fox, J.G., Erdman, S.E., Breast cancer: should gastrointestinal bacteria be on our radar screen?. Cancer Res. 67 (2007), 847–850.
9. [9] Dinan, T.G., Stanton, C., Cryan, J.F., Psychobiotics: a novel class of psychotropic. Biol. Psychiatry 74 (2013), 720–726.
10. [10] 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., Microbial symbionts accelerate wound healing via the neuropeptide hormone oxytocin. PLoS One, 8, 2013, e78898.
11. [11] Varian, B.J., Poutahidis, T., Levkovich, T., Ibrahim, Y.M., Lakritz, J.R., Chatzigiagkos, A., Scherer-Hoock, A., Alm, E.J., Erdman, S.E., Beneficial bacteria stimulate youthful thyroid gland activity. J. Obes. Weight Loss Ther. 4 (2014), 1–8.
12. [12] Varian, B.J., Goureshetti, S., Poutahidis, T., Lakritz, J.R., Levkovich, T., Kwok, C., Teliousis, K., Ibrahim, Y.M., Mirabal, S., Erdman, S.E., Beneficial bacteria inhibit cachexia. Oncotarget 7 (2016), 11803–11816.
13. [13] Eberl, G., Immunity by equilibrium. Nat. Rev. Immunol. 16 (2016), 524–532.
14. [14] Pittman, Q.J., A neuro-endocrine-immune symphony. J. Neuroendocrinol. 23 (2011), 1296–1297.
15. [15] Brestoff, J.R., Artis, D., Immune regulation of metabolic homeostasis in health and disease. Cell 161 (2015), 146–160.
16. [16] McCusker, R.H., Kelley, K.W., Immune-neural connections: how the immune system's response to infectious agents influences behavior. J. Exp. Biol. 216 (2013), 84–98.
17. [17] Hodes, G.E., Kana, V., Menard, C., Merad, M., Russo, S.J., Neuroimmune mechanisms of depression. Nat. Neurosci. 18 (2015), 1386–1393.
18. [18] DuPage, M., Bluestone, J.A., Harnessing the plasticity of CD4(+) T cells to treat immune-mediated disease. Nat. Rev. Immunol. 16 (2016), 149–163.
19. [19] Lorenzatti, A.J., Retzlaff, B.M., Unmet needs in the management of atherosclerotic cardiovascular disease: is there a role for emerging anti-inflammatory interventions?. Int. J. Cardiol. 221 (2016), 581–586.
20. [20] Rook, G.A., Dalgleish, A., Infection, immunoregulation, and cancer. Immunol. Rev. 240 (2011), 141–159.
21. [21] Kipnis, J., Multifaceted interactions between adaptive immunity and the central nervous system. Science 353 (2016), 766–771.
22. [22] Erdman, S.E., Poutahidis, T., Cancer inflammation and regulatory T cells. Int J. Cancer 127 (2010), 768–779.
23. [23] Erdman, S.E., Poutahidis, T., The microbiome modulates the tumor macroenvironment. Oncoimmunology(3), 2014.
24. [24] Balkwill, F., Charles, K.A., Mantovani, A., Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7 (2005), 211–217.
25. [25] Honda, K., Littman, D.R., The microbiota in adaptive immune homeostasis and disease. Nature 535 (2016), 75–84.
26. [26] Rook, G.A., Regulation of the immune system by biodiversity from the natural environment: an ecosystem service essential to health. Proc. Natl. Acad. Sci. USA 110 (2013), 18360–18367.
27. [27] Cryan, J.F., Dinan, T.G., Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat. Rev. Neurosci. 13 (2012), 701–712.
28. [28] Erdman, S.E., Poutahidis, T., Probiotic ‘glow of health’: it's more than skin deep. Benef. Microbes 5 (2014), 109–119.
29. [29] Sonnenburg, J.L., Backhed, F., Diet-microbiota interactions as moderators of human metabolism. Nature 535 (2016), 56–64.
30. [30] Arthur, J.C., Perez-Chanona, E., Muhlbauer, M., Tomkovich, S., Uronis, J.M., Fan, T.J., Campbell, B.J., Abujamel, T., Dogan, B., Rogers, A.B., Rhodes, J.M., Stintzi, A., Simpson, K.W., Hansen, J.J., Keku, T.O., Fodor, A.A., Jobin, C., Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338 (2012), 120–123.
31. [31] Sherwin, E., Rea, K., Dinan, T.G., Cryan, J.F., A gut (microbiome) feeling about the brain. Curr. Opin. Gastroenterol. 32 (2016), 96–102.
32. [32] Lillberg, K., Verkasalo, P.K., Kaprio, J., Teppo, L., Helenius, H., Koskenvuo, M., Stressful life events and risk of breast cancer in 10,808 women: a cohort study. Am. J. Epidemiol. 157 (2003), 415–423.
33. [33] Costanzo, E.S., Sood, A.K., Lutgendorf, S.K., Biobehavioral influences on cancer progression. Immunol. Allergy Clin. N Am. 31 (2011), 109–132.
34. [34] Powell, N.D., Tarr, A.J., Sheridan, J.F., Psychosocial stress and inflammation in cancer. Brain Behav. Immun. 30 Suppl: (2013), S41–47.
35. [35] Erdman, S.E., Poutahidis, T., Tomczak, M., Rogers, A.B., Cormier, K., Plank, B., Horwitz, B.H., Fox, J.G., CD4+ CD25+ regulatory T lymphocytes inhibit microbially induced colon cancer in Rag2-deficient mice. Am. J. Pathol. 162 (2003), 691–702.
36. [36] Rao, V.P., Poutahidis, T., Ge, Z., Nambiar, P.R., Boussahmain, C., Wang, Y.Y., Horwitz, B.H., Fox, J.G., Erdman, S.E., Innate immune inflammatory response against enteric bacteria Helicobacter hepaticus induces mammary adenocarcinoma in mice. Cancer Res. 66 (2006), 7395–7400.
37. [37] Lakritz, J.R., Poutahidis, T., Mirabal, S., Varian, B.J., Levkovich, T., Ibrahim, Y.M., Ward, J.M., Teng, E.C., Fisher, B., Parry, N., Lesage, S., Alberg, N., Gourishetti, S., Fox, J.G., Ge, Z., Erdman, S.E., Gut bacteria require neutrophils to promote mammary tumorigenesis. Oncotarget 6 (2015), 9387–9396.
38. [38] Shankaran, V., Ikeda, H., Bruce, A.T., White, J.M., Swanson, P.E., Old, L.J., Schreiber, R.D., IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410 (2001), 1107–1111.
39. [39] Poutahidis, T., Haigis, K.M., Rao, V.P., Nambiar, P.R., Taylor, C.L., Ge, Z., Watanabe, K., Davidson, A., Horwitz, B.H., Fox, J.G., Erdman, S.E., Rapid reversal of interleukin-6-dependent epithelial invasion in a mouse model of microbially induced colon carcinoma. Carcinogenesis 28 (2007), 2614–2623.
40. [40] Erdman, S.E., Rao, V.P., Olipitz, W., Taylor, C.L., Jackson, E.J., Levkovich, T., Lee, C.W., Horwitz, B.H., Fox, J.G., Ge, Z., Poutahidis, T., Unifying roles for regulatory T cells and inflammation in cancer. Int. J. Cancer 126 (2009), 1651–1665.
41. [41] Coffelt, S.B., de Visser KE, W.M., Neutrophils in cancer: neutral no more. Nat. Rev. Cancer, 16, 2016, 16.
42. [42] Erdman, S.E., Rao, V.P., Poutahidis, T., Rogers, A.B., Taylor, C.L., Jackson, E.A., Ge, Z., Lee, C.W., Schauer, D.B., Wogan, G.N., Tannenbaum, S.R., Fox, J.G., Nitric oxide and TNF-{alpha} trigger colonic inflammation and carcinogenesis in Helicobacter hepaticus-infected, Rag2-deficient mice. Proc. Natl. Acad. Sci. USA, 2009.
43. [43] Dumitru, C.A., Lang, S., Brandau, S., Modulation of neutrophil granulocytes in the tumor microenvironment: mechanisms and consequences for tumor progression. Semin Cancer Biol. 23 (2013), 141–148.
44. [44] Singel, K.L., Segal, B.H., Neutrophils in the tumor microenvironment: trying to heal the wound that cannot heal. Immunol. Rev. 273 (2016), 329–343.
45. [45] Gregory, A.D., Houghton, A.M., Tumor-associated neutrophils: new targets for cancer therapy. Cancer Res. 71 (2011), 2411–2416.
46. [46] Treffers, L.W., Hiemstra, I.H., Kuijpers, T.W., van den Berg, T.K., Matlung, H.L., Neutrophils in cancer. Immunol. Rev. 273 (2016), 312–328.
47. [47] Yang, X.D., Ai, W., Asfaha, S., Bhagat, G., Friedman, R.A., Jin, G., Park, H., Shykind, B., Diacovo, T.G., Falus, A., Wang, T.C., Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b(+)Ly6G(+) immature myeloid cells. Nat. Med. 17 (2011), 87–95.
48. [48] Poutahidis, T., Cappelle, K., Levkovich, T., Lee, C.W., Doulberis, M., Ge, Z., Fox, J.G., Horwitz, B.H., Erdman, S.E., Pathogenic intestinal bacteria enhance prostate cancer development via systemic activation of immune cells in mice. PLoS One(8), 2013, e73933.
49. [49] Fridlender, Z.G., Sun, J., Kim, S., Kapoor, V., Cheng, G., Ling, L., Worthen, G.S., Albelda, S.M., Polarization of tumor-associated neutrophil phenotype by TGF-beta: “n1” versus “N2” TAN. Cancer Cell 16 (2009), 183–194.
50. [50] Krstic, J., Trivanovic, D., Mojsilovic, S., Santibanez, J.F., Transforming growth factor-beta and oxidative stress interplay: implicationsimplications in tumorigenesis and cancer progression. Oxid. Med Cell Longev., 2015, 2015 654594.
51. [51] Round, J.L., Mazmanian, S.K., Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc. Natl. Acad. Sci. USA 107 (2010), 12204–12209.
52. [52] Ivanov, I.I., Atarashi, K., Manel, N., Brodie, E.L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K.C., Santee, C.A., Lynch, S.V., Tanoue, T., Imaoka, A., Itoh, K., Takeda, K., Umesaki, Y., Honda, K., Littman, D.R., Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139 (2009), 485–498.
53. [53] Atarashi, K., Tanoue, T., Oshima, K., Suda, W., Nagano, Y., Nishikawa, H., Fukuda, S., Saito, T., Narushima, S., Hase, K., Kim, S., Fritz, J.V., Wilmes, P., Ueha, S., Matsushima, K., Ohno, H., Olle, B., Sakaguchi, S., Taniguchi, T., Morita, H., Hattori, M., Honda, K., Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500 (2013), 232–236.
54. [54] Ohnmacht, C., Park, J.H., Cording, S., Wing, J.B., Atarashi, K., Obata, Y., Gaboriau-Routhiau, V., Marques, R., Dulauroy, S., Fedoseeva, M., Busslinger, M., Cerf-Bensussan, N., Boneca, I.G., Voehringer, D., Hase, K., Honda, K., Sakaguchi, S., Eberl, G., MUCOSAL IMMUNOLOGY. The microbiota regulates type 2 immunity through RORgammat(+) T cells. Science 349 (2015), 989–993.
55. [55] Lindner, C., Thomsen, I., Wahl, B., Ugur, M., Sethi, M.K., Friedrichsen, M., Smoczek, A., Ott, S., Baumann, U., Suerbaum, S., Schreiber, S., Bleich, A., Gaboriau-Routhiau, V., Cerf-Bensussan, N., Hazanov, H., Mehr, R., Boysen, P., Rosenstiel, P., Pabst, O., Diversification of memory B cells drives the continuous adaptation of secretory antibodies to gut microbiota. Nat. Immunol. 16 (2015), 880–888.
56. [56] Lathrop, S.K., Bloom, S.M., Rao, S.M., Nutsch, K., Lio, C.W., Santacruz, N., Peterson, D.A., Stappenbeck, T.S., Hsieh, C.S., Peripheral education of the immune system by colonic commensal microbiota. Nature 478 (2011), 250–254.
57. [57] Gaboriau-Routhiau, V., Rakotobe, S., Lecuyer, E., Mulder, I., Lan, A., Bridonneau, C., Rochet, V., Pisi, A., De Paepe, M., Brandi, G., Eberl, G., Snel, J., Kelly, D., Cerf-Bensussan, N., The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31 (2009), 677–689.
58. [58] Chow, J., Mazmanian, S.K., A pathobiont of the microbiota balances host colonization and intestinal inflammation. Cell Host Microbe 7 (2010), 265–276.
59. [59] Geuking, M.B., Cahenzli, J., Lawson, M.A., Ng, D.C., Slack, E., Hapfelmeier, S., McCoy, K.D., Macpherson, A.J., Intestinal bacterial colonization induces mutualistic regulatory T cell responses. Immunity 34 (2011), 794–806.
60. [60] Kullberg, M.C., Jankovic, D., Gorelick, P.L., Caspar, P., Letterio, J.J., Cheever, A.W., Sher, A., Bacteria-triggered CD4(+) T regulatory cells suppress Helicobacter hepaticus-induced colitis. J. Exp. Med. 196 (2002), 505–515.
61. [61] Powrie, F., Maloy, K.J., Immunology. Regulating the regulators. Science 299 (2003), 1030–1031.
62. [62] Erdman, S.E., Rao, V.P., Poutahidis, T., Ihrig, M.M., Ge, Z., Feng, Y., Tomczak, M., Rogers, A.B., Horwitz, B.H., Fox, J.G., CD4(+)CD25(+) regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice. Cancer Res. 63 (2003), 6042–6050.
63. [63] Poutahidis, T., Varian, B.J., Levkovich, T., Lakritz, J.R., Mirabal, S., Kwok, C., Ibrahim, Y.M., Kearney, S.M., Chatzigiagkos, A., Alm, E.J., Erdman, S.E., Dietary microbes modulate transgenerational cancer risk. Cancer Res. 75 (2015), 1197–1204.
64. [64] Malhotra, D., Linehan, J.L., Dileepan, T., Lee, Y.J., Purtha, W.E., Lu, J.V., Nelson, R.W., Fife, B.T., Orr, H.T., Anderson, M.S., Hogquist, K.A., Jenkins, M.K., Tolerance is established in polyclonal CD4(+) T cells by distinct mechanisms, according to self-peptide expression patterns. Nat. Immunol. 17 (2016), 187–195.
65. [65] Belkaid, Y., Hand, T.W., Role of the microbiota in immunity and inflammation. Cell 157 (2014), 121–141.
66. [66] Wing, K., Sakaguchi, S., Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat. Immunol. 11 (2010), 7–13.
67. [67] Nishioka, T., Shimizu, J., Iida, R., Yamazaki, S., Sakaguchi, S., CD4+CD25+Foxp3+ T cells and CD4+CD25-Foxp3+ T cells in aged mice. J. Immunol. 176 (2006), 6586–6593.
68. [68] van den Akker, T.W., Tio-Gillen, A.P., Solleveld, H.A., Benner, R., Radl, J., The influence of T cells on homogeneous immunoglobulins in sera of athymic nude mice during aging. Scand. J. Immunol. 28 (1988), 359–365.
69. [69] Palamaro, L., Romano, R., Fusco, A., Giardino, G., Gallo, V., Pignata, C., FOXN1 in organ development and human diseases. Int. Rev. Immunol. 33 (2014), 83–93.
70. [70] Khosravi, A., Yanez, A., Price, J.G., Chow, A., Merad, M., Goodridge, H.S., Mazmanian, S.K., Gut microbiota promote hematopoiesis to control bacterial infection. Cell Host Microbe 15 (2014), 374–381.
71. [71] Balmer, M.L., Schurch, C.M., Saito, Y., Geuking, M.B., Li, H., Cuenca, M., Kovtonyuk, L.V., McCoy, K.D., Hapfelmeier, S., Ochsenbein, A.F., Manz, M.G., Slack, E., Macpherson, A.J., Microbiota-derived compounds drive steady-state granulopoiesis via MyD88/TICAM signaling. J. Immunol. 193 (2014), 5273–5283.
72. [72] Trompette, A., Gollwitzer, E.S., Yadava, K., Sichelstiel, A.K., Sprenger, N., Ngom-Bru, C., Blanchard, C., Junt, T., Nicod, L.P., Harris, N.L., Marsland, B.J., Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat. Med. 20 (2014), 159–166.
73. [73] Gomez de Aguero, M., Ganal-Vonarburg, S.C., Fuhrer, T., Rupp, S., Uchimura, Y., Li, H., Steinert, A., Heikenwalder, M., Hapfelmeier, S., Sauer, U., McCoy, K.D., Macpherson, A.J., The maternal microbiota drives early postnatal innate immune development. Science 351 (2016), 1296–1302.
74. [74] Deshmukh, H.S., Liu, Y., Menkiti, O.R., Mei, J., Dai, N., O'Leary, C.E., Oliver, P.M., Kolls, J.K., Weiser, J.N., Worthen, G.S., The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice. Nat. Med. 20 (2014), 524–530.
75. [75] Mei, J., Liu, Y., Dai, N., Hoffmann, C., Hudock, K.M., Zhang, P., Guttentag, S.H., Kolls, J.K., Oliver, P.M., Bushman, F.D., Worthen, G.S., Cxcr2 and Cxcl5 regulate the IL-17/G-CSF axis and neutrophil homeostasis in mice. J. Clin. Investig. 122 (2012), 974–986.
76. [76] Zhang, D., Chen, G., Manwani, D., Mortha, A., Xu, C., Faith, J.J., Burk, R.D., Kunisaki, Y., Jang, J.E., Scheiermann, C., Merad, M., Frenette, P.S., Neutrophil ageing is regulated by the microbiome. Nature 525 (2015), 528–532.
77. [77] Varian, B.J., Levkovich, T., Poutahidis, T., Ibrahim, Y.M., Perrotta, A., Alm, E.J., Erdman, S.E., Beneficial dog bacteria up-regulate oxytocin and lower risk of obesity. J. Probiotics Health 4 (2016), 1–9.
78. [78] Varian, B.J., Poutahidis, T., DiBenedictis, B.T., Levkovich, T., Ibrahim, Y., Didyk, E., Shikhman, L., Cheung, H.K., Hardas, A., Ricciardi, C.E., Kolandaivelu, K., Veenema, A.H., Alm, E.J., Erdman, S.E., Microbial lysate upregulates host oxytocin. Brain Behav. Immun., 2016 In Press.
79. [79] Poutahidis, T., Kleinewietfeld, M., Smillie, C., Levkovich, T., Perrotta, A., Bhela, S., Varian, B.J., Ibrahim, Y.M., Lakritz, J.R., Kearney, S.M., Chatzigiagkos, A., Hafler, D.A., Alm, E.J., Erdman, S.E., Microbial reprogramming inhibits Western diet-associated obesity. PLoS One, 8, 2013, e68596.
80. [80] Levkovich, T., Poutahidis, T., Smillie, C., Varian, B.J., Ibrahim, Y.M., Lakritz, J.R., Alm, E.J., Erdman, S.E., Probiotic bacteria induce a ‘glow of health’. PLoS One, 8, 2013, e53867.
81. [81] Lakritz, J.R., Poutahidis, T., Levkovich, T., Varian, B.J., Ibrahim, Y.M., Chatzigiagkos, A., Mirabal, S., Alm, E.J., Erdman, S.E., Beneficial bacteria stimulate host immune cells to counteract dietary and genetic predisposition to mammary cancer in mice. Int J. Cancer 135 (2014), 529–540.
82. [82] Al-Amran, F., Shahkolahi, M., Oxytocin ameliorates the immediate myocardial injury in rat heart transplant through downregulation of neutrophil-dependent myocardial apoptosis. Transpl. Proc. 45 (2013), 2506–2512.
83. [83] Biyikli, N.K., Tugtepe, H., Sener, G., Velioglu-Ogunc, A., Cetinel, S., Midillioglu, S., Gedik, N., Yegen, B.C., Oxytocin alleviates oxidative renal injury in pyelonephritic rats via a neutrophil-dependent mechanism. Peptides 27 (2006), 2249–2257.
84. [84] Iseri, S.O., Sener, G., Saglam, B., Gedik, N., Ercan, F., Yegen, B.C., Oxytocin ameliorates oxidative colonic inflammation by a neutrophil-dependent mechanism. Peptides 26 (2005), 483–491.
85. [85] Iseri, S.O., Sener, G., Saglam, B., Gedik, N., Ercan, F., Yegen, B.C., Oxytocin protects against sepsis-induced multiple organ damage: role of neutrophils. J. Surg. Res. 126 (2005), 73–81.
86. [86] Petersson, M., Wiberg, U., Lundeberg, T., Uvnas-Moberg, K., Oxytocin decreases carrageenan induced inflammation in rats. Peptides 22 (2001), 1479–1484.
87. [87] Cheema, A.K., Maier, I., Dowdy, T., Wang, Y., Singh, R., Ruegger, P.M., Borneman, J., Fornace, A.J. Jr, Schiestl, R.H., Chemopreventive metabolites are correlated with a change in intestinal microbiota measured in A-T mice and decreased carcinogenesis. PLoS One, 11, 2016, e0151190.
88. [88] Rook, G.A., Review series on helminths, immune modulation and the hygiene hypothesis: the broader implications of the hygiene hypothesis. Immunology 126 (2009), 3–11.
89. [89] Molin, G., Jeppsson, B., Johansson, M.L., Ahrne, S., Nobaek, S., Stahl, M., Bengmark, S., Numerical taxonomy of Lactobacillus spp. associated with healthy and diseased mucosa of the human intestines. J. Appl. Bacteriol. 74 (1993), 314–323.
90. [90] Walter, J., Britton, R.A., Roos, S., Host-microbial symbiosis in the vertebrate gastrointestinal tract and the Lactobacillus reuteri paradigm. Proc. Natl. Acad. Sci. USA 108:Suppl. 1 (2011), 4645–4652.
91. [91] Poutahidis, T., Springer, A., Levkovich, T., Qi, P., Varian, B.J., Lakritz, J.R., Ibrahim, Y.M., Chatzigiagkos, A., Alm, E.J., Erdman, S.E., Probiotic microbes sustain youthful serum testosterone levels and testicular size in aging mice. PLoS One, 9, 2014, e84877.
92. [92] Nakajima, A., Negishi, N., Tsurui, H., Kadowaki-Ohtsuji, N., Maeda, K., Nanno, M., Yamaguchi, Y., Shimizu, N., Yagita, H., Okumura, K., Habu, S., Commensal bacteria regulate thymic Aire expression. PLoS One, 9, 2014, e105904.
93. [93] Valencia, X., Stephens, G., Goldbach-Mansky, R., Wilson, M., Shevach, E.M., Lipsky, P.E., TNF downmodulates the function of human CD4+CD25hi T-regulatory cells. Blood 108 (2006), 253–261.
94. [94] Cebula, A., Seweryn, M., Rempala, G.A., Pabla, S.S., McIndoe, R.A., Denning, T.L., Bry, L., Kraj, P., Kisielow, P., Ignatowicz, L., Thymus-derived regulatory T cells contribute to tolerance to commensal microbiota. Nature 497 (2013), 258–262.
95. [95] Wang, P., Yang, H.P., Tian, S., Wang, L., Wang, S.C., Zhang, F., Wang, Y.F., Oxytocin-secreting system: a major part of the neuroendocrine center regulating immunologic activity. J. Neuroimmunol. 289 (2015), 152–161.
96. [96] Geenen, V., Martens, H., Brilot, F., Renard, C., Franchimont, D., Kecha, O., Thymic neuroendocrine self-antigens. Role in T-cell development and central T-cell self-tolerance. Ann. NY Acad. Sci. 917 (2000), 710–723.
97. [97] Hansenne, I., Rasier, G., Pequeux, C., Brilot, F., Renard, C., Breton, C., Greimers, R., Legros, J.J., Geenen, V., Martens, H.J., Ontogenesis and functional aspects of oxytocin and vasopressin gene expression in the thymus network. J. Neuroimmunol. 158 (2005), 67–75.
98. [98] Gimpl, G., Fahrenholz, F., The oxytocin receptor system: structure, function, and regulation. Physiol. Rev. 81 (2001), 629–683.
99. [99] Hamasaki, M.Y., Barbeiro, H.V., Barbeiro, D.F., Cunha, D.M., Koike, M.K., Machado, M.C., Pinheiro da Silva, F., Neuropeptides in the brain defense against distant organ damage. J. Neuroimmunol. 290 (2016), 33–35.
100. [100] Yuan, L., Liu, S., Bai, X., Gao, Y., Liu, G., Wang, X., Liu, D., Li, T., Hao, A., Wang, Z., Oxytocin inhibits lipopolysaccharide-induced inflammation in microglial cells and attenuates microglial activation in lipopolysaccharide-treated mice. J. Neuroinflamm., 13, 2016, 77.
101. [101] Matsuura, T., Kawasaki, M., Hashimoto, H., Yoshimura, M., Motojima, Y., Saito, R., Ueno, H., Maruyama, T., Sabanai, K., Mori, T., Ohnishi, H., Sakai, A., Ueta, Y., Effects of central administration of oxytocin-saporin cytotoxin on chronic inflammation and feeding/drinking behaviors in adjuvant arthritic rats. Neurosci. Lett. 621 (2016), 104–110.
102. [102] Furusawa, Y., Obata, Y., Fukuda, S., Endo, T.A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., Takahashi, M., Fukuda, N.N., Murakami, S., Miyauchi, E., Hino, S., Atarashi, K., Onawa, S., Fujimura, Y., Lockett, T., Clarke, J.M., Topping, D.L., Tomita, M., Hori, S., Ohara, O., Morita, T., Koseki, H., Kikuchi, J., Honda, K., Hase, K., Ohno, H., Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504 (2013), 446–450.
103. [103] Smith, P.M., Howitt, M.R., Panikov, N., Michaud, M., Gallini, C.A., Bohlooly, Y.M., Glickman, J.N., Garrett, W.S., The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341 (2013), 569–573.
104. [104] Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., Liu, H., Cross, J.R., Pfeffer, K., Coffer, P.J., Rudensky, A.Y., Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504 (2013), 451–455.
105. [105] Wang, L., Liu, Y., Han, R., Beier, U.H., Bhatti, T.R., Akimova, T., Greene, M.I., Hiebert, S.W., Hancock, W.W., FOXP3+ regulatory T cell development and function require histone/protein deacetylase. J. Clin. Investig. 125:3 (2015), 1111–1123.
106. [106] Fontenelle, B., Gilbert, K.M., n-Butyrate anergized effector CD4+ T cells independent of regulatory T cell generation or activity. Scand. J. Immunol. 76 (2012), 457–463.
107. [107] Clemente, J.C., Ursell, L.K., Parfrey, L.W., Knight, R., The impact of the gut microbiota on human health: an integrative view. Cell 148 (2012), 1258–1270.
108. [108] Guilloteau, P., Martin, L., Eeckhaut, V., Ducatelle, R., Zabielski, R., Van Immerseel, F., From the gut to the peripheral tissues: the multiple effects of butyrate. Nutr. Res. Rev. 23 (2010), 366–384.
109. [109] Poutahidis, T., Erdman, S.E., Commensal bacteria modulate the tumor microenvironment. Cancer Lett., 2015.
110. [110] Vetizou, M., Pitt, J.M., Daillere, R., Lepage, P., Waldschmitt, N., Flament, C., Rusakiewicz, S., Routy, B., Roberti, M.P., Duong, C.P., Poirier-Colame, V., Roux, A., Becharef, S., Formenti, S., Golden, E., Cording, S., Eberl, G., Schlitzer, A., Ginhoux, F., Mani, S., Yamazaki, T., Jacquelot, N., Enot, D.P., Berard, M., Nigou, J., Opolon, P., Eggermont, A., Woerther, P.L., Chachaty, E., Chaput, N., Robert, C., Mateus, C., Kroemer, G., Raoult, D., Boneca, I.G., Carbonnel, F., Chamaillard, M., Zitvogel, L., Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350 (2015), 1079–1084.
111. [111] Sivan, A., Corrales, L., Hubert, N., Williams, J.B., Aquino-Michaels, K., Earley, Z.M., Benyamin, F.W., Lei, Y.M., Jabri, B., Alegre, M.L., Chang, E.B., Gajewski, T.F., Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350 (2015), 1084–1089.
112. [112] Northoff, H., Berg, A., Weinstock, C., Similarities and differences of the immune response to exercise and trauma: the IFN-gamma concept. Can. J. Physiol. Pharmacol. 76 (1998), 497–504.
113. [113] Tanno, H., Kawakami, K., Ritsu, M., Kanno, E., Suzuki, A., Kamimatsuno, R., Takagi, N., Miyasaka, T., Ishii, K., Imai, Y., Maruyama, R., Tachi, M., Contribution of invariant natural killer T cells to skin wound healing. Am. J. Pathol. 185 (2015), 3248–3257.
114. [114] Thelemann, C., Eren, R.O., Coutaz, M., Brasseit, J., Bouzourene, H., Rosa, M., Duval, A., Lavanchy, C., Mack, V., Mueller, C., Reith, W., Acha-Orbea, H., Interferon-gamma induces expression of MHC class II on intestinal epithelial cells and protects mice from colitis. PLoS One, 9, 2014, e86844.