The Enteric Network: Interactions between the Immune and Nervous Systems of the Gut

Immunity

Volumn 46, Issue 6, 2017, Pages 910-926

  Yoo, Bryan B ^a   Mazmanian, Sarkis K ^a  

^a California Institute of Technology   (United States)

Author keywords

enteric nervous system; gastrointestinal tract; gut brain axis; intestinal microbiota; neuro immune interactions; neuro immunity

Indexed keywords

ACETYLCHOLINE; CATECHOLAMINE; CYTOKINE; HISTAMINE; NEUROPEPTIDE; NEUROTROPHIC FACTOR; SEROTONIN; SHORT CHAIN FATTY ACID;

ANATOMY; BACTEROIDES; CENTRAL NERVOUS SYSTEM; ENVIRONMENT; GASTROINTESTINAL MUCOSA; GASTROINTESTINAL TRACT; HUMAN; IMMUNE RESPONSE; IMMUNE SYSTEM; INTESTINE; INTESTINE EPITHELIUM; INTESTINE INNERVATION; LACTOBACILLUS; MICROBIOME; NERVE CELL; NERVE CONDUCTION; NERVOUS SYSTEM; NERVOUS SYSTEM FUNCTION; NONHUMAN; PHYSIOLOGY; PRIORITY JOURNAL; REVIEW; TRICHINELLA SPIRALIS; ANATOMY AND HISTOLOGY; ANIMAL; ENVIRONMENTAL EXPOSURE; HOST PATHOGEN INTERACTION; IMMUNOLOGY; IMMUNOMODULATION; INTESTINE FLORA; MUCOSAL IMMUNITY;

ANIMALS; CENTRAL NERVOUS SYSTEM; ENTERIC NERVOUS SYSTEM; ENVIRONMENTAL EXPOSURE; GASTROINTESTINAL MICROBIOME; GASTROINTESTINAL TRACT; HOST-PATHOGEN INTERACTIONS; HUMANS; IMMUNE SYSTEM; IMMUNITY, MUCOSAL; INTESTINES; NEUROIMMUNOMODULATION;

EID: 85027566080     PISSN: 10747613     EISSN: 10974180     Source Type: Journal    
DOI: 10.1016/j.immuni.2017.05.011     Document Type: Review

References (226)

1. Aas, J., Gessert, C.E., Bakken, J.S., Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube. Clin. Infect. Dis. 36 (2003), 580–585.
2. Abad, C., Martinez, C., Juarranz, M.G., Arranz, A., Leceta, J., Delgado, M., Gomariz, R.P., Therapeutic effects of vasoactive intestinal peptide in the trinitrobenzene sulfonic acid mice model of Crohn's disease. Gastroenterology 124 (2003), 961–971.
3. Ahlman, H., Lundberg, J., Dahlström, A., Kewenter, J., A possible vagal adrenergic release of serotonin from enterochromaffin cells in the cat. Acta Physiol. Scand. 98 (1976), 366–375.
4. Ahmad, A., Wang, C.H., Bell, R.G., A role for IgE in intestinal immunity. Expression of rapid expulsion of Trichinella spiralis in rats transfused with IgE and thoracic duct lymphocytes. J. Immunol. 146 (1991), 3563–3570.
5. Amato, A., Cinci, L., Rotondo, A., Serio, R., Faussone-Pellegrini, M.S., Vannucchi, M.G., Mulè, F., Peripheral motor action of glucagon-like peptide-1 through enteric neuronal receptors. Neurogastroenterol. Motil., 22, 2010 664–e203.
6. Angrist, M., Bolk, S., Halushka, M., Lapchak, P.A., Chakravarti, A., Germline mutations in glial cell line-derived neurotrophic factor (GDNF) and RET in a Hirschsprung disease patient. Nat. Genet. 14 (1996), 341–344.
7. Anini, Y., Brubaker, P.L., Muscarinic receptors control glucagon-like peptide 1 secretion by human endocrine L cells. Endocrinology 144 (2003), 3244–3250.
8. Anitha, M., Chandrasekharan, B., Salgado, J.R., Grouzmann, E., Mwangi, S., Sitaraman, S.V., Srinivasan, S., Glial-derived neurotrophic factor modulates enteric neuronal survival and proliferation through neuropeptide Y. Gastroenterology 131 (2006), 1164–1178.
9. Anitha, M., Vijay-Kumar, M., Sitaraman, S.V., Gewirtz, A.T., Srinivasan, S., Gut microbial products regulate murine gastrointestinal motility via Toll-like receptor 4 signaling. Gastroenterology, 143, 2012 1006–16.e4.
10. Asano, Y., Hiramoto, T., Nishino, R., Aiba, Y., Kimura, T., Yoshihara, K., Koga, Y., Sudo, N., Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am. J. Physiol. Gastrointest. Liver Physiol. 303 (2012), G1288–G1295.
11. Atarashi, K., Tanoue, T., Shima, T., Imaoka, A., Kuwahara, T., Momose, Y., Cheng, G., Yamasaki, S., Saito, T., Ohba, Y., et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331 (2011), 337–341.
12. Atarashi, K., Tanoue, T., Oshima, K., Suda, W., Nagano, Y., Nishikawa, H., Fukuda, S., Saito, T., Narushima, S., Hase, K., et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500 (2013), 232–236.
13. Austin, K.M., The pathogenesis of Hirschsprung's disease-associated enterocolitis. Semin. Pediatr. Surg. 21 (2012), 319–327.
14. Ayabe, T., Satchell, D.P., Wilson, C.L., Parks, W.C., Selsted, M.E., Ouellette, A.J., Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat. Immunol. 1 (2000), 113–118.
15. Bär, K.J., Facer, P., Williams, N.S., Tam, P.K., Anand, P., Glial-derived neurotrophic factor in human adult and fetal intestine and in Hirschsprung's disease. Gastroenterology 112 (1997), 1381–1385.
16. Barajon, I., Serrao, G., Arnaboldi, F., Opizzi, E., Ripamonti, G., Balsari, A., Rumio, C., Toll-like receptors 3, 4, and 7 are expressed in the enteric nervous system and dorsal root ganglia. J. Histochem. Cytochem. 57 (2009), 1013–1023.
17. Barrett, E., Ross, R.P., O'Toole, P.W., Fitzgerald, G.F., Stanton, C., γ-Aminobutyric acid production by culturable bacteria from the human intestine. J. Appl. Microbiol. 113 (2012), 411–417.
18. Berthoud, H.-R., Powley, T.L., Characterization of vagal innervation to the rat celiac, suprarenal and mesenteric ganglia. J. Auton. Nerv. Syst. 42 (1993), 153–169.
19. Bevins, C.L., Salzman, N.H., Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat. Rev. Microbiol. 9 (2011), 356–368.
20. Birchenough, G.M.H., Nyström, E.E.L., Johansson, M.E.V., Hansson, G.C., A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion. Science 352 (2016), 1535–1542.
21. Bogunovic, M., Davé, S.H., Tilstra, J.S., Chang, D.T.W., Harpaz, N., Xiong, H., Mayer, L.F., Plevy, S.E., Enteroendocrine cells express functional Toll-like receptors. Am. J. Physiol. Gastrointest. Liver Physiol. 292 (2007), G1770–G1783.
22. Bohórquez, D.V., Shahid, R.A., Erdmann, A., Kreger, A.M., Wang, Y., Calakos, N., Wang, F., Liddle, R.A., Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells. J. Clin. Invest. 125 (2015), 782–786.
23. Borovikova, L.V., Ivanova, S., Zhang, M., Yang, H., Botchkina, G.I., Watkins, L.R., Wang, H., Abumrad, N., Eaton, J.W., Tracey, K.J., Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405 (2000), 458–462.
24. Bradley, J.S. Jr., Parr, E.J., Sharkey, K.A., Effects of inflammation on cell proliferation in the myenteric plexus of the guinea-pig ileum. Cell Tissue Res. 289 (1997), 455–461.
25. Bravo, J.A., Forsythe, P., Chew, M.V., Escaravage, E., Savignac, H.M., Dinan, T.G., Bienenstock, J., Cryan, J.F., Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc. Natl. Acad. Sci. USA 108 (2011), 16050–16055.
26. Bröer, S., Amino acid transport across mammalian intestinal and renal epithelia. Physiol. Rev. 88 (2008), 249–286.
27. Brooks, A.S., Oostra, B.A., Hofstra, R.M.W., Studying the genetics of Hirschsprung's disease: unraveling an oligogenic disorder. Clin. Genet. 67 (2005), 6–14.
28. Brown, D.R., Price, L.D., Catecholamines and sympathomimetic drugs decrease early Salmonella Typhimurium uptake into porcine Peyer's patches. FEMS Immunol. Med. Microbiol. 52 (2008), 29–35.
29. Brown, A.J., Goldsworthy, S.M., Barnes, A.A., Eilert, M.M., Tcheang, L., Daniels, D., Muir, A.I., Wigglesworth, M.J., Kinghorn, I., Fraser, N.J., et al. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem. 278 (2003), 11312–11319.
30. Brun, P., Giron, M.C., Qesari, M., Porzionato, A., Caputi, V., Zoppellaro, C., Banzato, S., Grillo, A.R., Spagnol, L., De Caro, R., et al. Toll-like receptor 2 regulates intestinal inflammation by controlling integrity of the enteric nervous system. Gastroenterology 145 (2013), 1323–1333.
31. Brun, P., Gobbo, S., Caputi, V., Spagnol, L., Schirato, G., Pasqualin, M., Levorato, E., Palù, G., Giron, M.C., Castagliuolo, I., Toll like receptor-2 regulates production of glial-derived neurotrophic factors in murine intestinal smooth muscle cells. Mol. Cell. Neurosci. 68 (2015), 24–35.
32. Buhner, S., Li, Q., Vignali, S., Barbara, G., De Giorgio, R., Stanghellini, V., Cremon, C., Zeller, F., Langer, R., Daniel, H., et al. Activation of human enteric neurons by supernatants of colonic biopsy specimens from patients with irritable bowel syndrome. Gastroenterology 137 (2009), 1425–1434.
33. Bülbring, E., Lin, R.C.Y., The effect of intraluminal application of 5-hydroxytryptamine and 5-hydroxytryptophan on peristalsis; the local production of 5-HT and its release in relation to intraluminal pressure and propulsive activity. J. Physiol. 140 (1958), 381–407.
34. Burgueño, J.F., Barba, A., Eyre, E., Romero, C., Neunlist, M., Fernández, E., TLR2 and TLR9 modulate enteric nervous system inflammatory responses to lipopolysaccharide. J. Neuroinflammation, 13, 2016, 187.
35. Burton-Freeman, B., Gietzen, D.W., Schneeman, B.O., Cholecystokinin and serotonin receptors in the regulation of fat-induced satiety in rats. Am. J. Physiol. 276 (1999), R429–R434.
36. Bush, T.G., Savidge, T.C., Freeman, T.C., Cox, H.J., Campbell, E.A., Mucke, L., Johnson, M.H., Sofroniew, M.V., Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice. Cell 93 (1998), 189–201.
37. Campbell, J.M., Fahey, G.C. Jr., Wolf, B.W., Selected indigestible oligosaccharides affect large bowel mass, cecal and fecal short-chain fatty acids, pH and microflora in rats. J. Nutr. 127 (1997), 130–136.
38. Carretta, M.D., Conejeros, I., Hidalgo, M.A., Burgos, R.A., Propionate induces the release of granules from bovine neutrophils. J. Dairy Sci. 96 (2013), 2507–2520.
39. Chang, R.B., Strochlic, D.E., Williams, E.K., Umans, B.D., Liberles, S.D., Vagal Sensory Neuron Subtypes that Differentially Control Breathing. Cell 161 (2015), 622–633.
40. Charney, A.N., Micic, L., Egnor, R.W., Nonionic diffusion of short-chain fatty acids across rat colon. Am. J. Physiol. 274 (1998), G518–G524.
41. Cherbut, C., Ferrier, L., Rozé, C., Anini, Y., Blottière, H., Lecannu, G., Galmiche, J.-P., Short-chain fatty acids modify colonic motility through nerves and polypeptide YY release in the rat. Am. J. Physiol. 275 (1998), G1415–G1422.
42. Chorny, A., Gonzalez-Rey, E., Fernandez-Martin, A., Pozo, D., Ganea, D., Delgado, M., Vasoactive intestinal peptide induces regulatory dendritic cells with therapeutic effects on autoimmune disorders. Proc. Natl. Acad. Sci. USA 102 (2005), 13562–13567.
43. Chu, H., Khosravi, A., Kusumawardhani, I.P., Kwon, A.H.K., Vasconcelos, A.C., Cunha, L.D., Mayer, A.E., Shen, Y., Wu, W.-L., Kambal, A., et al. Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease. Science 352 (2016), 1116–1120.
44. Clark, M.A., Hirst, B.H., Jepson, M.A., M-cell surface β1 integrin expression and invasin-mediated targeting of Yersinia pseudotuberculosis to mouse Peyer's patch M cells. Infect. Immun. 66 (1998), 1237–1243.
45. Collins, S.M., Hurst, S.M., Main, C., Stanley, E., Khan, I., Blennerhassett, P., Swain, M., Effect of inflammation of enteric nerves. Cytokine-induced changes in neurotransmitter content and release. Ann. N Y Acad. Sci. 664 (1992), 415–424.
46. Collins, J., Borojevic, R., Verdu, E.F., Huizinga, J.D., Ratcliffe, E.M., Intestinal microbiota influence the early postnatal development of the enteric nervous system. Neurogastroenterol. Motil. 26 (2014), 98–107.
47. Conlin, V.S., Wu, X., Nguyen, C., Dai, C., Vallance, B.A., Buchan, A.M.J., Boyer, L., Jacobson, K., Vasoactive intestinal peptide ameliorates intestinal barrier disruption associated with Citrobacter rodentium-induced colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 297 (2009), G735–G750.
48. Costa, M., Furness, J.B., The sites of action of 5-hydroxytryptamine in nerve-muscle preparations from the guinea-pig small intestine and colon. Br. J. Pharmacol. 65 (1979), 237–248.
49. Covasa, M., Duca, F.A., Swartz, T.D., Gut Microbiota Restores Central Neuropeptide Deficits Present in Germ Free Animals. FASEB J., 30, 2016, 1166.9.
50. Csaba, G., Kapa, E., Cserhalmi, M., Hormone receptor studies on frog macrophage cells by means of histamine, serotonin and indoleacetic acid. Endokrinologie 65 (1975), 219–223.
51. De la Fuente, M., Bernaez, I., Del Rio, M., Hernanz, A., Stimulation of murine peritoneal macrophage functions by neuropeptide Y and peptide YY. Involvement of protein kinase C. Immunology 80 (1993), 259–265.
52. de las Casas-Engel, M., Domínguez-Soto, A., Sierra-Filardi, E., Bragado, R., Nieto, C., Puig-Kroger, A., Samaniego, R., Loza, M., Corcuera, M.T., Gómez-Aguado, F., et al. Serotonin skews human macrophage polarization through HTR2B and HTR7. J. Immunol. 190 (2013), 2301–2310.
53. Delgado, M., Munoz-Elias, E.J., Gomariz, R.P., Ganea, D., Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide enhance IL-10 production by murine macrophages: in vitro and in vivo studies. J. Immunol. 162 (1999), 1707–1716.
54. Delgado, M., Chorny, A., Gonzalez-Rey, E., Ganea, D., Vasoactive intestinal peptide generates CD4+CD25+ regulatory T cells in vivo. J. Leukoc. Biol. 78 (2005), 1327–1338.
55. Delgado, M., Gonzalez-Rey, E., Ganea, D., The neuropeptide vasoactive intestinal peptide generates tolerogenic dendritic cells. J. Immunol. 175 (2005), 7311–7324.
56. Derrien, M., Vaughan, E.E., Plugge, C.M., de Vos, W.M., Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int. J. Syst. Evol. Microbiol. 54 (2004), 1469–1476.
57. Dhawan, S., De Palma, G., Willemze, R.A., Hilbers, F.W., Verseijden, C., Luyer, M.D., Nuding, S., Wehkamp, J., Souwer, Y., de Jong, E.C., et al. Acetylcholine-producing T cells in the intestine regulate antimicrobial peptide expression and microbial diversity. Am. J. Physiol. Gastrointest. Liver Physiol. 311 (2016), G920–G933.
58. Diakos, C., Prieschl, E.E., Säemann, M.D., Böhmig, G.A., Csonga, R., Sobanov, Y., Baumruker, T., Zlabinger, G.J., n-Butyrate inhibits Jun NH(2)-terminal kinase activation and cytokine transcription in mast cells. Biochem. Biophys. Res. Commun. 349 (2006), 863–868.
59. Diaz Heijtz, R., Wang, S., Anuar, F., Qian, Y., Björkholm, B., Samuelsson, A., Hibberd, M.L., Forssberg, H., Pettersson, S., Normal gut microbiota modulates brain development and behavior. Proc. Natl. Acad. Sci. USA 108 (2011), 3047–3052.
60. Digby, J.E., Martinez, F., Jefferson, A., Ruparelia, N., Chai, J., Wamil, M., Greaves, D.R., Choudhury, R.P., Anti-inflammatory effects of nicotinic acid in human monocytes are mediated by GPR109A dependent mechanisms. Arterioscler. Thromb. Vasc. Biol. 32 (2012), 669–676.
61. Dubos, R.J., Schaedler, R.W., The effect of the intestinal flora on the growth rate of mice, and on their susceptibility to experimental infections. J. Exp. Med. 111 (1960), 407–417.
62. Duca, F.A., Swartz, T.D., Sakar, Y., Covasa, M., Increased oral detection, but decreased intestinal signaling for fats in mice lacking gut microbiota. PLoS ONE, 7, 2012, e39748.
63. Eftimiadi, C., Buzzi, E., Tonetti, M., Buffa, P., Buffa, D., van Steenbergen, M.T., de Graaff, J., Botta, G.A., Short-chain fatty acids produced by anaerobic bacteria alter the physiological responses of human neutrophils to chemotactic peptide. J. Infect. 14 (1987), 43–53.
64. Elenkov, I.J., Wilder, R.L., Chrousos, G.P., Vizi, E.S., The sympathetic nerve–an integrative interface between two supersystems: the brain and the immune system. Pharmacol. Rev. 52 (2000), 595–638.
65. Erspamer, V., Asero, B., Identification of enteramine, the specific hormone of the enterochromaffin cell system, as 5-hydroxytryptamine. Nature 169 (1952), 800–801.
66. Espinosa-Medina, I., Saha, O., Boismoreau, F., Chettouh, Z., Rossi, F., Richardson, W.D., Brunet, J.F., The sacral autonomic outflow is sympathetic. Science 354 (2016), 893–897.
67. Foligne, B., Nutten, S., Grangette, C., Dennin, V., Goudercourt, D., Poiret, S., Dewulf, J., Brassart, D., Mercenier, A., Pot, B., Correlation between in vitro and in vivo immunomodulatory properties of lactic acid bacteria. World J. Gastroenterol. 13 (2007), 236–243.
68. Foster, N., Lea, S.R., Preshaw, P.M., Taylor, J.J., Pivotal advance: vasoactive intestinal peptide inhibits up-regulation of human monocyte TLR2 and TLR4 by LPS and differentiation of monocytes to macrophages. J. Leukoc. Biol. 81 (2007), 893–903.
69. Frieling, T., Palmer, J.M., Cooke, H.J., Wood, J.D., Neuroimmune communication in the submucous plexus of guinea pig colon after infection with Trichinella spiralis. Gastroenterology 107 (1994), 1602–1609.
70. Fujimoto, T., Reen, D.J., Puri, P., Inflammatory response in enterocolitis in the piebald lethal mouse model of Hirschsprung's disease. Pediatr. Res. 24 (1988), 152–155.
71. Furness, J.B., The enteric nervous system and neurogastroenterology. Nat. Rev. Gastroenterol. Hepatol. 9 (2012), 286–294.
72. Furness, J.B., Costa, M., Types of nerves in the enteric nervous system. Neuroscience 5 (1980), 1–20.
73. Furness, J.B., Callaghan, B.P., Rivera, L.R., Cho, H.-J., The enteric nervous system and gastrointestinal innervation: integrated local and central control. Adv. Exp. Med. Biol. 817 (2014), 39–71.
74. Furusawa, Y., Obata, Y., Fukuda, S., Endo, T.A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504 (2013), 446–450.
75. Gabanyi, I., Muller, P.A., Feighery, L., Oliveira, T.Y., Costa-Pinto, F.A., Mucida, D., Neuro-immune Interactions Drive Tissue Programming in Intestinal Macrophages. Cell 164 (2016), 378–391.
76. Gadelle, D., Raibaud, P., Sacquet, E., beta-Glucuronidase activities of intestinal bacteria determined both in vitro and in vivo in gnotobiotic rats. Appl. Environ. Microbiol. 49 (1985), 682–685.
77. Ganea, D., Gonzalez-Rey, E., Delgado, M., A novel mechanism for immunosuppression: from neuropeptides to regulatory T cells. J. Neuroimmune Pharmacol. 1 (2006), 400–409.
78. Gerbe, F., Sidot, E., Smyth, D.J., Ohmoto, M., Matsumoto, I., Dardalhon, V., Cesses, P., Garnier, L., Pouzolles, M., Brulin, B., et al. Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites. Nature 529 (2016), 226–230.
79. Gianino, S., Grider, J.R., Cresswell, J., Enomoto, H., Heuckeroth, R.O., GDNF availability determines enteric neuron number by controlling precursor proliferation. Development 130 (2003), 2187–2198.
80. Gomariz, R.P., Arranz, A., Abad, C., Torroba, M., Martinez, C., Rosignoli, F., Garcia-Gómez, M., Leceta, J., Juarranz, Y., Time-course expression of Toll-like receptors 2 and 4 in inflammatory bowel disease and homeostatic effect of VIP. J. Leukoc. Biol. 78 (2005), 491–502.
81. Grasa, L., Abecia, L., Forcén, R., Castro, M., de Jalón, J.A.G., Latorre, E., Alcalde, A.I., Murillo, M.D., Antibiotic-Induced Depletion of Murine Microbiota Induces Mild Inflammation and Changes in Toll-Like Receptor Patterns and Intestinal Motility. Microb. Ecol. 70 (2015), 835–848.
82. Gribble, F.M., Reimann, F., Enteroendocrine Cells: Chemosensors in the Intestinal Epithelium. Annu. Rev. Physiol. 78 (2016), 277–299.
83. Grubišić, V., Gulbransen, B.D., Enteric glial activity regulates secretomotor function in the mouse colon but does not acutely affect gut permeability. J. Physiol., 2017, 10.1113/JP273492.
84. Grundy, D., Brookes, S., Neural Control of Gastrointestinal Function, Colloquium Series on Integrated Systems Physiology: From Molecule to Function. 2011, Morgan & Claypool Publishers.
85. Gunawardene, A.R., Corfe, B.M., Staton, C.A., Classification and functions of enteroendocrine cells of the lower gastrointestinal tract. Int. J. Exp. Pathol. 92 (2011), 219–231.
86. Gustafsson, J.K., Ermund, A., Johansson, M.E.V., Schütte, A., Hansson, G.C., Sjövall, H., An ex vivo method for studying mucus formation, properties, and thickness in human colonic biopsies and mouse small and large intestinal explants. Am. J. Physiol. Gastrointest. Liver Physiol. 302 (2012), G430–G438.
87. Gutknecht, L., Kriegebaum, C., Waider, J., Schmitt, A., Lesch, K.-P., Spatio-temporal expression of tryptophan hydroxylase isoforms in murine and human brain: convergent data from Tph2 knockout mice. Eur. Neuropsychopharmacol. 19 (2009), 266–282.
88. Hadjifrangiskou, M., Kostakioti, M., Chen, S.L., Henderson, J.P., Greene, S.E., Hultgren, S.J., A central metabolic circuit controlled by QseC in pathogenic Escherichia coli. Mol. Microbiol. 80 (2011), 1516–1529.
89. Haghikia, A., Jörg, S., Duscha, A., Berg, J., Manzel, A., Waschbisch, A., Hammer, A., Lee, D.-H., May, C., Wilck, N., et al. Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine. Immunity 43 (2015), 817–829.
90. Han, T.Y., Lourenssen, S., Miller, K.G., Blennerhassett, M.G., Intestinal smooth muscle phenotype determines enteric neuronal survival via GDNF expression. Neuroscience 290 (2015), 357–368.
91. Hansen, G.H., Niels-Christiansen, L.L., Immerdal, L., Hunziker, W., Kenny, A.J., Danielsen, E.M., Transcytosis of immunoglobulin A in the mouse enterocyte occurs through glycolipid raft- and rab17-containing compartments. Gastroenterology 116 (1999), 610–622.
92. Hayes, M.R., Chory, F.M., Gallagher, C.A., Covasa, M., Serotonin type-3 receptors mediate cholecystokinin-induced satiation through gastric distension. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291 (2006), R115–R123.
93. Heanue, T.A., Pachnis, V., Expression profiling the developing mammalian enteric nervous system identifies marker and candidate Hirschsprung disease genes. Proc. Natl. Acad. Sci. USA 103 (2006), 6919–6924.
94. Helander, H.F., Fändriks, L., Surface area of the digestive tract - revisited. Scand. J. Gastroenterol. 49 (2014), 681–689.
95. Herrera, J.L., Gonzalez-Rey, E., Fernandez-Montesinos, R., Quintana, F.J., Najmanovich, R., Pozo, D., Toll-like receptor stimulation differentially regulates vasoactive intestinal peptide type 2 receptor in macrophages. J. Cell. Mol. Med. 13:9B (2009), 3209–3217.
96. Heuckeroth, R.O., Enomoto, H., Grider, J.R., Golden, J.P., Hanke, J.A., Jackman, A., Molliver, D.C., Bardgett, M.E., Snider, W.D., Johnson, E.M. Jr., Milbrandt, J., Gene targeting reveals a critical role for neurturin in the development and maintenance of enteric, sensory, and parasympathetic neurons. Neuron 22 (1999), 253–263.
97. Hillsley, K., Grundy, D., Sensitivity to 5-hydroxytryptamine in different afferent subpopulations within mesenteric nerves supplying the rat jejunum. J. Physiol. 509 (1998), 717–727.
98. Hira, T., Nakajima, S., Eto, Y., Hara, H., Calcium-sensing receptor mediates phenylalanine-induced cholecystokinin secretion in enteroendocrine STC-1 cells. FEBS J. 275 (2008), 4620–4626.
99. Hoban, A.E., Stilling, R.M., Ryan, F.J., Shanahan, F., Dinan, T.G., Claesson, M.J., Clarke, G., Cryan, J.F., Regulation of prefrontal cortex myelination by the microbiota. Transl. Psychiatry, 6, 2016, e774.
100. Hooper, L.V., Wong, M.H., Thelin, A., Hansson, L., Falk, P.G., Gordon, J.I., Molecular analysis of commensal host-microbial relationships in the intestine. Science 291 (2001), 881–884.
101. Howitt, M.R., Lavoie, S., Michaud, M., Blum, A.M., Tran, S.V., Weinstock, J.V., Gallini, C.A., Redding, K., Margolskee, R.F., Osborne, L.C., et al. Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science 351 (2016), 1329–1333.
102. Hsiao, E.Y., McBride, S.W., Hsien, S., Sharon, G., Hyde, E.R., McCue, T., Codelli, J.A., Chow, J., Reisman, S.E., Petrosino, J.F., et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155 (2013), 1451–1463.
103. Hurst, S.M., Stanisz, A.M., Sharkey, K.A., Collins, S.M., Interleukin-1-Beta Induced Increase in Substance-P in Rat Myenteric Plexus. Gastroenterology 105 (1993), 1754–1760.
104. Ibiza, S., García-Cassani, B., Ribeiro, H., Carvalho, T., Almeida, L., Marques, R., Misic, A.M., Bartow-McKenney, C., Larson, D.M., Pavan, W.J., et al. Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence. Nature 535 (2016), 440–443.
105. Imamura, A., Puri, P., O'Briain, D.S., Reen, D.J., Mucosal immune defence mechanisms in enterocolitis complicating Hirschsprung's disease. Gut 33 (1992), 801–806.
106. Ishizaka, T., Hirata, F., Ishizaka, K., Axelrod, J., Stimulation of phospholipid methylation, Ca2+ influx, and histamine release by bridging of IgE receptors on rat mast cells. Proc. Natl. Acad. Sci. USA 77 (1980), 1903–1906.
107. Johansson, M.E.V., Hansson, G.C., Immunological aspects of intestinal mucus and mucins. Nat. Rev. Immunol. 16 (2016), 639–649.
108. Kabouridis, P.S., Lasrado, R., McCallum, S., Chng, S.H., Snippert, H.J., Clevers, H., Pettersson, S., Pachnis, V., Microbiota controls the homeostasis of glial cells in the gut lamina propria. Neuron 85 (2015), 289–295.
109. Kagnoff, M.F., 1987. Immunology of the digestive system. Physiology of the gastrointestinal tract.
110. Kalff, J.C., Schwarz, N.T., Walgenbach, K.J., Schraut, W.H., Bauer, A.J., Leukocytes of the intestinal muscularis: their phenotype and isolation. J. Leukoc. Biol. 63 (1998), 683–691.
111. Karaki, S., Mitsui, R., Hayashi, H., Kato, I., Sugiya, H., Iwanaga, T., Furness, J.B., Kuwahara, A., Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine. Cell Tissue Res. 324 (2006), 353–360.
112. Kelly, D., Campbell, J.I., King, T.P., Grant, G., Jansson, E.A., Coutts, A.G.P., Pettersson, S., Conway, S., Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA. Nat. Immunol. 5 (2004), 104–112.
113. Kim, M.H., Kang, S.G., Park, J.H., Yanagisawa, M., Kim, C.H., Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterology 145 (2013), 396–406.e1 10.
114. King, C.D., Rios, G.R., Green, M.D., Tephly, T.R., UDP-glucuronosyltransferases. Curr. Drug Metab. 1 (2000), 143–161.
115. Kunze, W.A., Mao, Y.K., Wang, B., Huizinga, J.D., Ma, X., Forsythe, P., Bienenstock, J., Lactobacillus reuteri enhances excitability of colonic AH neurons by inhibiting calcium-dependent potassium channel opening. J. Cell. Mol. Med. 13:8B (2009), 2261–2270.
116. Le Poul, E., Loison, C., Struyf, S., Springael, J.-Y., Lannoy, V., Decobecq, M.-E., Brezillon, S., Dupriez, V., Vassart, G., Van Damme, J., et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J. Biol. Chem. 278 (2003), 25481–25489.
117. Lelievre, V., Favrais, G., Abad, C., Adle-Biassette, H., Lu, Y., Germano, P.M., Cheung-Lau, G., Pisegna, J.R., Gressens, P., Lawson, G., Waschek, J.A., Gastrointestinal dysfunction in mice with a targeted mutation in the gene encoding vasoactive intestinal polypeptide: a model for the study of intestinal ileus and Hirschsprung's disease. Peptides 28 (2007), 1688–1699.
118. Lelouard, H., Fallet, M., de Bovis, B., Méresse, S., Gorvel, J.P., Peyer's patch dendritic cells sample antigens by extending dendrites through M cell-specific transcellular pores. Gastroenterology 142 (2012), 592–601.e3.
119. León-Ponte, M., Ahern, G.P., O'Connell, P.J., Serotonin provides an accessory signal to enhance T-cell activation by signaling through the 5-HT7 receptor. Blood 109 (2007), 3139–3146.
120. Levite, M., Neuropeptides, by direct interaction with T cells, induce cytokine secretion and break the commitment to a distinct T helper phenotype. Proc. Natl. Acad. Sci. USA 95 (1998), 12544–12549.
121. Ley, R.E., Hamady, M., Lozupone, C., Turnbaugh, P.J., Ramey, R.R., Bircher, J.S., Schlegel, M.L., Tucker, T.A., Schrenzel, M.D., Knight, R., Gordon, J.I., Evolution of mammals and their gut microbes. Science 320 (2008), 1647–1651.
122. Li, Z.S., Pham, T.D., Tamir, H., Chen, J.J., Gershon, M.D., Enteric dopaminergic neurons: definition, developmental lineage, and effects of extrinsic denervation. J. Neurosci. 24 (2004), 1330–1339.
123. Li, Y., Xiao, B., Qiu, W., Yang, L., Hu, B., Tian, X., Yang, H., Altered expression of CD4(+)CD25(+) regulatory T cells and its 5-HT(1a) receptor in patients with major depression disorder. J. Affect. Disord. 124 (2010), 68–75.
124. Liang, S.C., Tan, X.-Y., Luxenberg, D.P., Karim, R., Dunussi-Joannopoulos, K., Collins, M., Fouser, L.A., Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J. Exp. Med. 203 (2006), 2271–2279.
125. Ligumsky, M., Simon, P.L., Karmeli, F., Rachmilewitz, D., Role of interleukin 1 in inflammatory bowel disease–enhanced production during active disease. Gut 31 (1990), 686–689.
126. Lin, Q., Submerged fermentation of Lactobacillus rhamnosus YS9 for γ-aminobutyric acid (GABA) production. Braz. J. Microbiol. 44 (2013), 183–187.
127. Lindemans, C.A., Calafiore, M., Mertelsmann, A.M., O'Connor, M.H., Dudakov, J.A., Jenq, R.R., Velardi, E., Young, L.F., Smith, O.M., Lawrence, G., et al. Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. Nature 528 (2015), 560–564.
128. Lotz, M., Vaughan, J.H., Carson, D.A., Effect of neuropeptides on production of inflammatory cytokines by human monocytes. Science 241 (1988), 1218–1221.
129. Lozupone, C.A., Stombaugh, J.I., Gordon, J.I., Jansson, J.K., Knight, R., Diversity, stability and resilience of the human gut microbiota. Nature 489 (2012), 220–230.
130. Lv, Y., Feng, M., Che, T., Sun, H., Luo, Y., Liu, K., Liu, C., CCK mediated the inhibitory effect of oxytocin on the contraction of longitudinal muscle strips of duodenum in male rats. Pflugers Arch. 460 (2010), 1063–1071.
131. Macpherson, A.J., Gatto, D., Sainsbury, E., Harriman, G.R., Hengartner, H., Zinkernagel, R.M., A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science 288 (2000), 2222–2226.
132. Madsen, K.L., Doyle, J.S., Jewell, L.D., Tavernini, M.M., Fedorak, R.N., Lactobacillus species prevents colitis in interleukin 10 gene-deficient mice. Gastroenterology 116 (1999), 1107–1114.
133. Mantyh, C.R., Gates, T.S., Zimmerman, R.P., Welton, M.L., Passaro, E.P. Jr., Vigna, S.R., Maggio, J.E., Kruger, L., Mantyh, P.W., Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed in high concentrations by arterioles, venules, and lymph nodules in surgical specimens obtained from patients with ulcerative colitis and Crohn disease. Proc. Natl. Acad. Sci. USA 85 (1988), 3235–3239.
134. Mao, Y.K., Kasper, D.L., Wang, B., Forsythe, P., Bienenstock, J., Kunze, W.A., Bacteroides fragilis polysaccharide A is necessary and sufficient for acute activation of intestinal sensory neurons. Nat. Commun., 4, 2013, 1465.
135. Matsumura, K., Miki, T., Jhomori, T., Gonoi, T., Seino, S., Possible role of PEPT1 in gastrointestinal hormone secretion. Biochem. Biophys. Res. Commun. 336 (2005), 1028–1032.
136. Mazmanian, S.K., Liu, C.H., Tzianabos, A.O., Kasper, D.L., An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122 (2005), 107–118.
137. Mazmanian, S.K., Round, J.L., Kasper, D.L., A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453 (2008), 620–625.
138. McDermott, J.R., Leslie, F.C., D'Amato, M., Thompson, D.G., Grencis, R.K., McLaughlin, J.T., Immune control of food intake: enteroendocrine cells are regulated by CD4+ T lymphocytes during small intestinal inflammation. Gut 55 (2006), 492–497.
139. McDole, J.R., Wheeler, L.W., McDonald, K.G., Wang, B., Konjufca, V., Knoop, K.A., Newberry, R.D., Miller, M.J., Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Nature 483 (2012), 345–349.
140. McLean, L.P., Smith, A., Cheung, L., Sun, R., Grinchuk, V., Vanuytsel, T., Desai, N., Urban, J.F. Jr., Zhao, A., Raufman, J.-P., Shea-Donohue, T., Type 3 Muscarinic Receptors Contribute to Clearance of Citrobacter rodentium. Inflamm. Bowel Dis. 21 (2015), 1860–1871.
141. McLean, L.P., Smith, A., Cheung, L., Urban, J.F., Sun, R., Grinchuk, V., Desai, N., Zhao, A., Raufman, J.-P., Shea-Donohue, T., Type 3 Muscarinic Receptors Contribute to Intestinal Mucosal Homeostasis and Clearance of Nippostrongylus brasiliensis through Induction of Th2 Cytokines. Am. J. Physiol. Gastrointest. Liver Physiol. 311 (2016), G130–G141.
142. McVey Neufeld, K.A., Mao, Y.K., Bienenstock, J., Foster, J.A., Kunze, W.A., The microbiome is essential for normal gut intrinsic primary afferent neuron excitability in the mouse. Neurogastroenterol. Motil., 25, 2013 183–e88.
143. Merchant, J.L., Tales from the crypts: regulatory peptides and cytokines in gastrointestinal homeostasis and disease. J. Clin. Invest. 117 (2007), 6–12.
144. Meredith, E.J., Holder, M.J., Chamba, A., Challa, A., Drake-Lee, A., Bunce, C.M., Drayson, M.T., Pilkington, G., Blakely, R.D., Dyer, M.J., et al. The serotonin transporter (SLC6A4) is present in B-cell clones of diverse malignant origin: probing a potential anti-tumor target for psychotropics. FASEB J. 19 (2005), 1187–1189.
145. Mongardi Fantaguzzi, C., Thacker, M., Chiocchetti, R., Furness, J.B., Identification of neuron types in the submucosal ganglia of the mouse ileum. Cell Tissue Res. 336 (2009), 179–189.
146. Moreira, C.G., Sperandio, V., Interplay between the QseC and QseE bacterial adrenergic sensor kinases in Salmonella enterica serovar Typhimurium pathogenesis. Infect. Immun. 80 (2012), 4344–4353.
147. Moreira, C.G., Russell, R., Mishra, A.A., Narayanan, S., Ritchie, J.M., Waldor, M.K., Curtis, M.M., Winter, S.E., Weinshenker, D., Sperandio, V., Bacterial Adrenergic Sensors Regulate Virulence of Enteric Pathogens in the Gut. MBio, 7, 2016 e00826-16.
148. Murphy, F., Puri, P., New insights into the pathogenesis of Hirschsprung's associated enterocolitis. Pediatr. Surg. Int. 21 (2005), 773–779.
149. Nassif, A., Longo, W.E., Sexe, R., Stratton, M., Standeven, J., Vernava, A.M., Kaminski, D.L., Clostridium difficile suppresses colonic vasoactive intestinal peptide associated with altered motility. Mediators Inflamm. 4 (1995), 452–453.
150. Neunlist, M., Dobreva, G., Schemann, M., Characteristics of mucosally projecting myenteric neurones in the guinea-pig proximal colon. J. Physiol. 517 (1999), 533–546.
151. Neunlist, M., Barouk, J., Michel, K., Just, I., Oreshkova, T., Schemann, M., Galmiche, J.P., Toxin B of Clostridium difficile activates human VIP submucosal neurons, in part via an IL-1beta-dependent pathway. Am. J. Physiol. Gastrointest. Liver Physiol. 285 (2003), G1049–G1055.
152. Ngu, M.C., Activation of enteric nerve pathways in the guinea-pig duodenum by cholecystokinin octapeptide and pentagastrin. J. Physiol. 364 (1985), 31–43.
153. Njoroge, J., Sperandio, V., Enterohemorrhagic Escherichia coli virulence regulation by two bacterial adrenergic kinases, QseC and QseE. Infect. Immun. 80 (2012), 688–703.
154. Nogueira, A.M., Barbosa, A.J., Immunocytochemical study of intestinal endocrine cells in germ-free mice. Eur. J. Histochem. 38 (1994), 213–218.
155. Nøhr, M.K., Pedersen, M.H., Gille, A., Egerod, K.L., Engelstoft, M.S., Husted, A.S., Sichlau, R.M., Grunddal, K.V., Poulsen, S.S., Han, S., et al. GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. Endocrinology 154 (2013), 3552–3564.
156. O'Connell, P.J., Wang, X., Leon-Ponte, M., Griffiths, C., Pingle, S.C., Ahern, G.P., A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells. Blood 107 (2006), 1010–1017.
157. O'Hara, J.R., Skinn, A.C., MacNaughton, W.K., Sherman, P.M., Sharkey, K.A., Consequences of Citrobacter rodentium infection on enteroendocrine cells and the enteric nervous system in the mouse colon. Cell. Microbiol. 8 (2006), 646–660.
158. Orland, F.J., Blayney, J.R., Harrison, R.W., Reyniers, J.A., Trexler, P.C., Wagner, M., Gordon, H.A., Luckey, T.D., Use of the germfree animal technic in the study of experimental dental caries. I. Basic observations on rats reared free of all microorganisms. J. Dent. Res. 33 (1954), 147–174.
159. Pácha, J., Development of intestinal transport function in mammals. Physiol. Rev. 80 (2000), 1633–1667.
160. Palazzo, M., Balsari, A., Rossini, A., Selleri, S., Calcaterra, C., Gariboldi, S., Zanobbio, L., Arnaboldi, F., Shirai, Y.F., Serrao, G., Rumio, C., Activation of enteroendocrine cells via TLRs induces hormone, chemokine, and defensin secretion. J. Immunol. 178 (2007), 4296–4303.
161. Patel, A., Harker, N., Moreira-Santos, L., Ferreira, M., Alden, K., Timmis, J., Foster, K., Garefalaki, A., Pachnis, P., Andrews, P., et al. Differential RET signaling pathways drive development of the enteric lymphoid and nervous systems. Sci. Signal., 5, 2012, ra55.
162. Peery, A.F., Dellon, E.S., Lund, J., Crockett, S.D., McGowan, C.E., Bulsiewicz, W.J., Gangarosa, L.M., Thiny, M.T., Stizenberg, K., Morgan, D.R., et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology, 143, 2012 1179–87.e1, 3.
163. Perez-Burgos, A., Wang, B., Mao, Y.K., Mistry, B., McVey Neufeld, K.A., Bienenstock, J., Kunze, W., Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents. Am. J. Physiol. Gastrointest. Liver Physiol. 304 (2013), G211–G220.
164. Psichas, A., Sleeth, M.L., Murphy, K.G., Brooks, L., Bewick, G.A., Hanyaloglu, A.C., Ghatei, M.A., Bloom, S.R., Frost, G., The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int. J. Obes. 39 (2015), 424–429.
165. Rakhilin, N., Barth, B., Choi, J., Muñoz, N.L., Kulkarni, S., Jones, J.S., Small, D.M., Cheng, Y.T., Cao, Y., LaVinka, C., et al. Simultaneous optical and electrical in vivo analysis of the enteric nervous system. Nat. Commun., 7, 2016, 11800.
166. Rapport, M.M., Green, A.A., Page, I.H., Serum vasoconstrictor, serotonin; isolation and characterization. J. Biol. Chem. 176 (1948), 1243–1251.
167. Reigstad, C.S., Salmonson, C.E., Rainey, J.F. 3rd, Szurszewski, J.H., Linden, D.R., Sonnenburg, J.L., Farrugia, G., Kashyap, P.C., Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J. 29 (2015), 1395–1403.
168. Reimann, F., Tolhurst, G., Gribble, F.M., G-protein-coupled receptors in intestinal chemosensation. Cell Metab. 15 (2012), 421–431.
169. Rescigno, M., Urbano, M., Valzasina, B., Francolini, M., Rotta, G., Bonasio, R., Granucci, F., Kraehenbuhl, J.-P., Ricciardi-Castagnoli, P., Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2 (2001), 361–367.
170. Reyniers, J.A., The use of germ-free guinea pigs in bacteriology. Proc. Ind. Acad. Sci. 42 (1932), 35–37.
171. Rosas-Ballina, M., Ochani, M., Parrish, W.R., Ochani, K., Harris, Y.T., Huston, J.M., Chavan, S., Tracey, K.J., Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia. Proc. Natl. Acad. Sci. USA 105 (2008), 11008–11013.
172. Rosas-Ballina, M., Olofsson, P.S., Ochani, M., Valdés-Ferrer, S.I., Levine, Y.A., Reardon, C., Tusche, M.W., Pavlov, V.A., Andersson, U., Chavan, S., et al. Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science 334 (2011), 98–101.
173. 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.
174. Rubin, D.C., Zhang, H., Qian, P., Lorenz, R.G., Hutton, K., Peters, M.G., Altered enteroendocrine cell expression in T cell receptor alpha chain knock-out mice. Microsc. Res. Tech. 51 (2000), 112–120.
175. Rudd, M.L., Nicolas, A.N., Brown, B.L., Fischer-Stenger, K., Stewart, J.K., Peritoneal macrophages express the serotonin transporter. J. Neuroimmunol. 159 (2005), 113–118.
176. Rühl, A., Franzke, S., Stremmel, W., IL-1β and IL-10 have dual effects on enteric glial cell proliferation. Neurogastroenterol. Motil. 13 (2001), 89–94.
177. Sampson, T.R., Debelius, J.W., Thron, T., Janssen, S., Shastri, G.G., Ilhan, Z.E., Challis, C., Schretter, C.E., Rocha, S., Gradinaru, V., et al. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell 167 (2016), 1469–1480.e12.
178. Samuel, B.S., Shaito, A., Motoike, T., Rey, F.E., Bäckhed, F., Manchester, J.K., Hammer, R.E., Williams, S.C., Crowley, J., Yanagisawa, M., Gordon, J.I., Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc. Natl. Acad. Sci. USA 105 (2008), 16767–16772.
179. Sánchez, M.P., Silos-Santiago, I., Frisén, J., He, B., Lira, S.A., Barbacid, M., Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 382 (1996), 70–73.
180. Satoh, Y., Atropine inhibits the degranulation of Paneth cells in ex-germ-free mice. Cell Tissue Res. 253 (1988), 397–402.
181. Satoh, Y., Ishikawa, K., Ono, K., Vollrath, L., Quantitative light microscopic observations on Paneth cells of germ-free and ex-germ-free Wistar rats. Digestion 34 (1986), 115–121.
182. Satoh, Y., Ishikawa, K., Oomori, Y., Takeda, S., Ono, K., Bethanechol and a G-protein activator, NaF/AlCl3, induce secretory response in Paneth cells of mouse intestine. Cell Tissue Res. 269 (1992), 213–220.
183. Schäfer, K.-H., Mestres, P., März, P., Rose-John, S., The IL-6/sIL-6R fusion protein hyper-IL-6 promotes neurite outgrowth and neuron survival in cultured enteric neurons. J. Interferon Cytokine Res. 19 (1999), 527–532.
184. Schéle, E., Grahnemo, L., Anesten, F., Hallén, A., Bäckhed, F., Jansson, J.-O., The gut microbiota reduces leptin sensitivity and the expression of the obesity-suppressing neuropeptides proglucagon (Gcg) and brain-derived neurotrophic factor (Bdnf) in the central nervous system. Endocrinology 154 (2013), 3643–3651.
185. Scheller, J., Chalaris, A., Schmidt-Arras, D., Rose-John, S., The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim. Biophys. Acta 1813 (2011), 878–888.
186. Schuchardt, A., D'Agati, V., Larsson-Blomberg, L., Costantini, F., Pachnis, V., Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 367 (1994), 380–383.
187. Sender, R., Fuchs, S., Milo, R., Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans. Cell 164 (2016), 337–340.
188. Serafini, N., Vosshenrich, C.A.J., Di Santo, J.P., Transcriptional regulation of innate lymphoid cell fate. Nat. Rev. Immunol. 15 (2015), 415–428.
189. Shajib, M.S., Khan, W.I., The role of serotonin and its receptors in activation of immune responses and inflammation. Acta Physiol. (Oxf.) 213 (2015), 561–574.
190. Singh, N., Gurav, A., Sivaprakasam, S., Brady, E., Padia, R., Shi, H., Thangaraju, M., Prasad, P.D., Manicassamy, S., Munn, D.H., et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40 (2014), 128–139.
191. Siragusa, S., De Angelis, M., Di Cagno, R., Rizzello, C.G., Coda, R., Gobbetti, M., Synthesis of gamma-aminobutyric acid by lactic acid bacteria isolated from a variety of Italian cheeses. Appl. Environ. Microbiol. 73 (2007), 7283–7290.
192. 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.
193. Song, J., Zhang, L., Bai, T., Qian, W., Li, R., Hou, X., Mast Cell-dependent Mesenteric Afferent Activation by Mucosal Supernatant From Different Bowel Segments of Guinea Pigs With Post-infectious Irritable Bowel Syndrome. J. Neurogastroenterol. Motil. 21 (2015), 236–246.
194. Sonnenberg, G.F., Monticelli, L.A., Elloso, M.M., Fouser, L.A., Artis, D., CD4(+) lymphoid tissue-inducer cells promote innate immunity in the gut. Immunity 34 (2011), 122–134.
195. Soret, R., Chevalier, J., De Coppet, P., Poupeau, G., Derkinderen, P., Segain, J.P., Neunlist, M., Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats. Gastroenterology 138 (2010), 1772–1782.
196. Stadnyk, A.W., Kearsey, J.A., Pattern of proinflammatory cytokine mRNA expression during Trichinella spiralis infection of the rat. Infect. Immun. 64 (1996), 5138–5143.
197. Stanisz, A.M., Befus, D., Bienenstock, J., Differential effects of vasoactive intestinal peptide, substance P, and somatostatin on immunoglobulin synthesis and proliferations by lymphocytes from Peyer's patches, mesenteric lymph nodes, and spleen. J. Immunol. 136 (1986), 152–156.
198. Starke-Buzetti, W.A., Oaks, J.A., Increased glial-derived neurotrophic factor in the small intestine of rats infected with the tapeworm, Hymenolepis diminuta. Int. J. Exp. Pathol. 89 (2008), 458–465.
199. Starodub, A.M., Wood, J.D., Histamine suppresses A-type potassium current in myenteric neurons from guinea pig small intestine. J. Pharmacol. Exp. Ther. 294 (2000), 555–561.
200. Stefulj, J., Jernej, B., Cicin-Sain, L., Rinner, I., Schauenstein, K., mRNA expression of serotonin receptors in cells of the immune tissues of the rat. Brain Behav. Immun. 14 (2000), 219–224.
201. Sternini, C., Anselmi, L., Rozengurt, E., Enteroendocrine cells: a site of ‘taste’ in gastrointestinal chemosensing. Curr. Opin. Endocrinol. Diabetes Obes. 15 (2008), 73–78.
202. Sugimoto, K., Ogawa, A., Mizoguchi, E., Shimomura, Y., Andoh, A., Bhan, A.K., Blumberg, R.S., Xavier, R.J., Mizoguchi, A., IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J. Clin. Invest. 118 (2008), 534–544.
203. Sun, W., Tadmori, I., Yang, L., Delgado, M., Ganea, D., Vasoactive intestinal peptide (VIP) inhibits TGF-β1 production in murine macrophages. J. Neuroimmunol. 107 (2000), 88–99.
204. Tazoe, H., Otomo, Y., Kaji, I., Tanaka, R., Karaki, S.I., Kuwahara, A., Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions. J. Physiol. Pharmacol. 59:Suppl 2 (2008), 251–262.
205. Thangaraju, M., Cresci, G.A., Liu, K., Ananth, S., Gnanaprakasam, J.P., Browning, D.D., Mellinger, J.D., Smith, S.B., Digby, G.J., Lambert, N.A., et al. GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res. 69 (2009), 2826–2832.
206. Theoharides, T.C., Bondy, P.K., Tsakalos, N.D., Askenase, P.W., Differential release of serotonin and histamine from mast cells. Nature 297 (1982), 229–231.
207. Vaishnava, S., Yamamoto, M., Severson, K.M., Ruhn, K.A., Yu, X., Koren, O., Ley, R., Wakeland, E.K., Hooper, L.V., The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine. Science 334 (2011), 255–258.
208. Valeur, N., Engel, P., Carbajal, N., Connolly, E., Ladefoged, K., Colonization and immunomodulation by Lactobacillus reuteri ATCC 55730 in the human gastrointestinal tract. Appl. Environ. Microbiol. 70 (2004), 1176–1181.
209. Vallance, B.A., Blennerhassett, P.A., Collins, S.M., Increased intestinal muscle contractility and worm expulsion in nematode-infected mice. Am. J. Physiol. 272 (1997), G321–G327.
210. van der Waaij, D., Berghuis-de Vries, J.M., Lekkerkerk Lekkerkerk-v, Colonization resistance of the digestive tract in conventional and antibiotic-treated mice. J. Hyg. (Lond.) 69 (1971), 405–411.
211. van der Waaij, L.A., Limburg, P.C., Mesander, G., van der Waaij, D., In vivo IgA coating of anaerobic bacteria in human faeces. Gut 38 (1996), 348–354.
212. Veiga-Fernandes, H., Coles, M.C., Foster, K.E., Patel, A., Williams, A., Natarajan, D., Barlow, A., Pachnis, V., Kioussis, D., Tyrosine kinase receptor RET is a key regulator of Peyer's patch organogenesis. Nature 446 (2007), 547–551.
213. von Boyen, G.B., Schulte, N., Pflüger, C., Spaniol, U., Hartmann, C., Steinkamp, M., Distribution of enteric glia and GDNF during gut inflammation. BMC Gastroenterol., 11, 2011, 3.
214. Vulchanova, L., Casey, M.A., Crabb, G.W., Kennedy, W.R., Brown, D.R., Anatomical evidence for enteric neuroimmune interactions in Peyer's patches. J. Neuroimmunol. 185 (2007), 64–74.
215. Wang, H., Yu, M., Ochani, M., Amella, C.A., Tanovic, M., Susarla, S., Li, J.H., Wang, H., Yang, H., Ulloa, L., et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421 (2003), 384–388.
216. Wang, Z., Friedrich, C., Hagemann, S.C., Korte, W.H., Goharani, N., Cording, S., Eberl, G., Sparwasser, T., Lochner, M., Regulatory T cells promote a protective Th17-associated immune response to intestinal bacterial infection with C. rodentium. Mucosal Immunol. 7 (2014), 1290–1301.
217. Wheway, J., Mackay, C.R., Newton, R.A., Sainsbury, A., Boey, D., Herzog, H., Mackay, F., A fundamental bimodal role for neuropeptide Y1 receptor in the immune system. J. Exp. Med. 202 (2005), 1527–1538.
218. Wolin, M.J., Fermentation in the rumen and human large intestine. Science 213 (1981), 1463–1468.
219. Wright, K.A., Trichinella spiralis: an intracellular parasite in the intestinal phase. J. Parasitol. 65 (1979), 441–445.
220. Xavier, R.J., Podolsky, D.K., Unravelling the pathogenesis of inflammatory bowel disease. Nature 448 (2007), 427–434.
221. Xia, Y., Hu, H.-Z., Liu, S., Ren, J., Zafirov, D.H., Wood, J.D., IL-1β and IL-6 excite neurons and suppress nicotinic and noradrenergic neurotransmission in guinea pig enteric nervous system. J. Clin. Invest. 103 (1999), 1309–1316.
222. Yamasaki, Y., Shimamura, O., Kizu, A., Nakagawa, M., Ijichi, H., Modulation by alpha 2-adrenergic stimulation of IgE-mediated 14C-serotonin release from rat mast cells. Agents Actions 13 (1983), 310–317.
223. Yano, J.M., Yu, K., Donaldson, G.P., Shastri, G.G., Ann, P., Ma, L., Nagler, C.R., Ismagilov, R.F., Mazmanian, S.K., Hsiao, E.Y., Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161 (2015), 264–276.
224. Yissachar, N., Zhou, Y., Ung, L., Lai, N.Y., Mohan, J.F., Ehrlicher, A., Weitz, D.A., Kasper, D.L., Chiu, I.M., Mathis, D., Benoist, C., An Intestinal Organ Culture System Uncovers a Role for the Nervous System in Microbe-Immune Crosstalk. Cell 168 (2017), 1135–1148.e12.
225. Zhao, A., McDermott, J., Urban, J.F. Jr., Gause, W., Madden, K.B., Yeung, K.A., Morris, S.C., Finkelman, F.D., Shea-Donohue, T., Dependence of IL-4, IL-13, and nematode-induced alterations in murine small intestinal smooth muscle contractility on Stat6 and enteric nerves. J. Immunol. 171 (2003), 948–954.
226. Zheng, Y., Valdez, P.A., Danilenko, D.M., Hu, Y., Sa, S.M., Gong, Q., Abbas, A.R., Modrusan, Z., Ghilardi, N., de Sauvage, F.J., Ouyang, W., Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat. Med. 14 (2008), 282–289.