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

Immunity - Tập 46 Số 6 - Trang 910-926 - 2017
Bryan B. Yoo1, Sarkis K. Mazmanian1
1Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA

Tóm tắt

Từ khóa


Tài liệu tham khảo

Aas, 2003, Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube, Clin. Infect. Dis., 36, 580, 10.1086/367657

Abad, 2003, Therapeutic effects of vasoactive intestinal peptide in the trinitrobenzene sulfonic acid mice model of Crohn’s disease, Gastroenterology, 124, 961, 10.1053/gast.2003.50141

Ahlman, 1976, A possible vagal adrenergic release of serotonin from enterochromaffin cells in the cat, Acta Physiol. Scand., 98, 366, 10.1111/j.1748-1716.1976.tb10321.x

Ahmad, 1991, 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, 3563, 10.4049/jimmunol.146.10.3563

Amato, 2010, Peripheral motor action of glucagon-like peptide-1 through enteric neuronal receptors, Neurogastroenterol. Motil., 22, 10.1111/j.1365-2982.2010.01476.x

Angrist, 1996, Germline mutations in glial cell line-derived neurotrophic factor (GDNF) and RET in a Hirschsprung disease patient, Nat. Genet., 14, 341, 10.1038/ng1196-341

Anini, 2003, Muscarinic receptors control glucagon-like peptide 1 secretion by human endocrine L cells, Endocrinology, 144, 3244, 10.1210/en.2003-0143

Anitha, 2006, Glial-derived neurotrophic factor modulates enteric neuronal survival and proliferation through neuropeptide Y, Gastroenterology, 131, 1164, 10.1053/j.gastro.2006.07.019

Anitha, 2012, Gut microbial products regulate murine gastrointestinal motility via Toll-like receptor 4 signaling, Gastroenterology, 143, 10.1053/j.gastro.2012.06.034

Asano, 2012, 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, G1288, 10.1152/ajpgi.00341.2012

Atarashi, 2011, Induction of colonic regulatory T cells by indigenous Clostridium species, Science, 331, 337, 10.1126/science.1198469

Atarashi, 2013, Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota, Nature, 500, 232, 10.1038/nature12331

Austin, 2012, The pathogenesis of Hirschsprung’s disease-associated enterocolitis, Semin. Pediatr. Surg., 21, 319, 10.1053/j.sempedsurg.2012.07.006

Ayabe, 2000, Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria, Nat. Immunol., 1, 113, 10.1038/77783

Bär, 1997, Glial-derived neurotrophic factor in human adult and fetal intestine and in Hirschsprung’s disease, Gastroenterology, 112, 1381, 10.1016/S0016-5085(97)70154-9

Barajon, 2009, Toll-like receptors 3, 4, and 7 are expressed in the enteric nervous system and dorsal root ganglia, J. Histochem. Cytochem., 57, 1013, 10.1369/jhc.2009.953539

Barrett, 2012, γ-Aminobutyric acid production by culturable bacteria from the human intestine, J. Appl. Microbiol., 113, 411, 10.1111/j.1365-2672.2012.05344.x

Berthoud, 1993, Characterization of vagal innervation to the rat celiac, suprarenal and mesenteric ganglia, J. Auton. Nerv. Syst., 42, 153, 10.1016/0165-1838(93)90046-W

Bevins, 2011, Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis, Nat. Rev. Microbiol., 9, 356, 10.1038/nrmicro2546

Birchenough, 2016, A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion, Science, 352, 1535, 10.1126/science.aaf7419

Bogunovic, 2007, Enteroendocrine cells express functional Toll-like receptors, Am. J. Physiol. Gastrointest. Liver Physiol., 292, G1770, 10.1152/ajpgi.00249.2006

Bohórquez, 2015, Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells, J. Clin. Invest., 125, 782, 10.1172/JCI78361

Borovikova, 2000, Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin, Nature, 405, 458, 10.1038/35013070

Bradley, 1997, Effects of inflammation on cell proliferation in the myenteric plexus of the guinea-pig ileum, Cell Tissue Res., 289, 455, 10.1007/s004410050891

Bravo, 2011, 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, 16050, 10.1073/pnas.1102999108

Bröer, 2008, Amino acid transport across mammalian intestinal and renal epithelia, Physiol. Rev., 88, 249, 10.1152/physrev.00018.2006

Brooks, 2005, Studying the genetics of Hirschsprung’s disease: unraveling an oligogenic disorder, Clin. Genet., 67, 6, 10.1111/j.1399-0004.2004.00319.x

Brown, 2008, Catecholamines and sympathomimetic drugs decrease early Salmonella Typhimurium uptake into porcine Peyer’s patches, FEMS Immunol. Med. Microbiol., 52, 29, 10.1111/j.1574-695X.2007.00348.x

Brown, 2003, The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids, J. Biol. Chem., 278, 11312, 10.1074/jbc.M211609200

Brun, 2013, Toll-like receptor 2 regulates intestinal inflammation by controlling integrity of the enteric nervous system, Gastroenterology, 145, 1323, 10.1053/j.gastro.2013.08.047

Brun, 2015, Toll like receptor-2 regulates production of glial-derived neurotrophic factors in murine intestinal smooth muscle cells, Mol. Cell. Neurosci., 68, 24, 10.1016/j.mcn.2015.03.018

Buhner, 2009, Activation of human enteric neurons by supernatants of colonic biopsy specimens from patients with irritable bowel syndrome, Gastroenterology, 137, 1425, 10.1053/j.gastro.2009.07.005

Bülbring, 1958, 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, 381, 10.1113/jphysiol.1958.sp005940

Burgueño, 2016, TLR2 and TLR9 modulate enteric nervous system inflammatory responses to lipopolysaccharide, J. Neuroinflammation, 13, 187, 10.1186/s12974-016-0653-0

Burton-Freeman, 1999, Cholecystokinin and serotonin receptors in the regulation of fat-induced satiety in rats, Am. J. Physiol., 276, R429

Bush, 1998, Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice, Cell, 93, 189, 10.1016/S0092-8674(00)81571-8

Campbell, 1997, Selected indigestible oligosaccharides affect large bowel mass, cecal and fecal short-chain fatty acids, pH and microflora in rats, J. Nutr., 127, 130, 10.1093/jn/127.1.130

Carretta, 2013, Propionate induces the release of granules from bovine neutrophils, J. Dairy Sci., 96, 2507, 10.3168/jds.2012-6111

Chang, 2015, Vagal Sensory Neuron Subtypes that Differentially Control Breathing, Cell, 161, 622, 10.1016/j.cell.2015.03.022

Charney, 1998, Nonionic diffusion of short-chain fatty acids across rat colon, Am. J. Physiol., 274, G518

Cherbut, 1998, Short-chain fatty acids modify colonic motility through nerves and polypeptide YY release in the rat, Am. J. Physiol., 275, G1415

Chorny, 2005, Vasoactive intestinal peptide induces regulatory dendritic cells with therapeutic effects on autoimmune disorders, Proc. Natl. Acad. Sci. USA, 102, 13562, 10.1073/pnas.0504484102

Chu, 2016, Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease, Science, 352, 1116, 10.1126/science.aad9948

Clark, 1998, M-cell surface β1 integrin expression and invasin-mediated targeting of Yersinia pseudotuberculosis to mouse Peyer’s patch M cells, Infect. Immun., 66, 1237, 10.1128/IAI.66.3.1237-1243.1998

Collins, 1992, Effect of inflammation of enteric nerves. Cytokine-induced changes in neurotransmitter content and release, Ann. N Y Acad. Sci., 664, 415, 10.1111/j.1749-6632.1992.tb39780.x

Collins, 2014, Intestinal microbiota influence the early postnatal development of the enteric nervous system, Neurogastroenterol. Motil., 26, 98, 10.1111/nmo.12236

Conlin, 2009, Vasoactive intestinal peptide ameliorates intestinal barrier disruption associated with Citrobacter rodentium-induced colitis, Am. J. Physiol. Gastrointest. Liver Physiol., 297, G735, 10.1152/ajpgi.90551.2008

Costa, 1979, The sites of action of 5-hydroxytryptamine in nerve-muscle preparations from the guinea-pig small intestine and colon, Br. J. Pharmacol., 65, 237, 10.1111/j.1476-5381.1979.tb07824.x

Covasa, 2016, Gut Microbiota Restores Central Neuropeptide Deficits Present in Germ Free Animals, FASEB J., 30, 1166.9, 10.1096/fasebj.30.1_supplement.1166.9

Csaba, 1975, Hormone receptor studies on frog macrophage cells by means of histamine, serotonin and indoleacetic acid, Endokrinologie, 65, 219

De la Fuente, 1993, Stimulation of murine peritoneal macrophage functions by neuropeptide Y and peptide YY. Involvement of protein kinase C, Immunology, 80, 259

de las Casas-Engel, 2013, Serotonin skews human macrophage polarization through HTR2B and HTR7, J. Immunol., 190, 2301, 10.4049/jimmunol.1201133

Delgado, 1999, 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, 1707, 10.4049/jimmunol.162.3.1707

Delgado, 2005, Vasoactive intestinal peptide generates CD4+CD25+ regulatory T cells in vivo, J. Leukoc. Biol., 78, 1327, 10.1189/jlb.0605299

Delgado, 2005, The neuropeptide vasoactive intestinal peptide generates tolerogenic dendritic cells, J. Immunol., 175, 7311, 10.4049/jimmunol.175.11.7311

Derrien, 2004, Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium, Int. J. Syst. Evol. Microbiol., 54, 1469, 10.1099/ijs.0.02873-0

Dhawan, 2016, Acetylcholine-producing T cells in the intestine regulate antimicrobial peptide expression and microbial diversity, Am. J. Physiol. Gastrointest. Liver Physiol., 311, G920, 10.1152/ajpgi.00114.2016

Diakos, 2006, n-Butyrate inhibits Jun NH(2)-terminal kinase activation and cytokine transcription in mast cells, Biochem. Biophys. Res. Commun., 349, 863, 10.1016/j.bbrc.2006.08.117

Diaz Heijtz, 2011, Normal gut microbiota modulates brain development and behavior, Proc. Natl. Acad. Sci. USA, 108, 3047, 10.1073/pnas.1010529108

Digby, 2012, Anti-inflammatory effects of nicotinic acid in human monocytes are mediated by GPR109A dependent mechanisms, Arterioscler. Thromb. Vasc. Biol., 32, 669, 10.1161/ATVBAHA.111.241836

Dubos, 1960, The effect of the intestinal flora on the growth rate of mice, and on their susceptibility to experimental infections, J. Exp. Med., 111, 407, 10.1084/jem.111.3.407

Duca, 2012, Increased oral detection, but decreased intestinal signaling for fats in mice lacking gut microbiota, PLoS ONE, 7, e39748, 10.1371/journal.pone.0039748

Eftimiadi, 1987, Short-chain fatty acids produced by anaerobic bacteria alter the physiological responses of human neutrophils to chemotactic peptide, J. Infect., 14, 43, 10.1016/S0163-4453(87)90808-5

Elenkov, 2000, The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system, Pharmacol. Rev., 52, 595

Erspamer, 1952, Identification of enteramine, the specific hormone of the enterochromaffin cell system, as 5-hydroxytryptamine, Nature, 169, 800, 10.1038/169800b0

Espinosa-Medina, 2016, The sacral autonomic outflow is sympathetic, Science, 354, 893, 10.1126/science.aah5454

Foligne, 2007, Correlation between in vitro and in vivo immunomodulatory properties of lactic acid bacteria, World J. Gastroenterol., 13, 236, 10.3748/wjg.v13.i2.236

Foster, 2007, 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, 893, 10.1189/jlb.0206086

Frieling, 1994, Neuroimmune communication in the submucous plexus of guinea pig colon after infection with Trichinella spiralis, Gastroenterology, 107, 1602, 10.1016/0016-5085(94)90798-6

Fujimoto, 1988, Inflammatory response in enterocolitis in the piebald lethal mouse model of Hirschsprung’s disease, Pediatr. Res., 24, 152, 10.1203/00006450-198808000-00002

Furness, 2012, The enteric nervous system and neurogastroenterology, Nat. Rev. Gastroenterol. Hepatol., 9, 286, 10.1038/nrgastro.2012.32

Furness, 1980, Types of nerves in the enteric nervous system, Neuroscience, 5, 1, 10.1016/0306-4522(80)90067-6

Furness, 2014, The enteric nervous system and gastrointestinal innervation: integrated local and central control, Adv. Exp. Med. Biol., 817, 39, 10.1007/978-1-4939-0897-4_3

Furusawa, 2013, Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells, Nature, 504, 446, 10.1038/nature12721

Gabanyi, 2016, Neuro-immune Interactions Drive Tissue Programming in Intestinal Macrophages, Cell, 164, 378, 10.1016/j.cell.2015.12.023

Gadelle, 1985, beta-Glucuronidase activities of intestinal bacteria determined both in vitro and in vivo in gnotobiotic rats, Appl. Environ. Microbiol., 49, 682, 10.1128/aem.49.3.682-685.1985

Ganea, 2006, A novel mechanism for immunosuppression: from neuropeptides to regulatory T cells, J. Neuroimmune Pharmacol., 1, 400, 10.1007/s11481-006-9044-0

Gerbe, 2016, Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites, Nature, 529, 226, 10.1038/nature16527

Gianino, 2003, GDNF availability determines enteric neuron number by controlling precursor proliferation, Development, 130, 2187, 10.1242/dev.00433

Gomariz, 2005, Time-course expression of Toll-like receptors 2 and 4 in inflammatory bowel disease and homeostatic effect of VIP, J. Leukoc. Biol., 78, 491, 10.1189/jlb.1004564

Grasa, 2015, Antibiotic-Induced Depletion of Murine Microbiota Induces Mild Inflammation and Changes in Toll-Like Receptor Patterns and Intestinal Motility, Microb. Ecol., 70, 835, 10.1007/s00248-015-0613-8

Gribble, 2016, Enteroendocrine Cells: Chemosensors in the Intestinal Epithelium, Annu. Rev. Physiol., 78, 277, 10.1146/annurev-physiol-021115-105439

Grubišić, 2017, Enteric glial activity regulates secretomotor function in the mouse colon but does not acutely affect gut permeability, J. Physiol., 10.1113/JP273492

Grundy, 2011

Gunawardene, 2011, Classification and functions of enteroendocrine cells of the lower gastrointestinal tract, Int. J. Exp. Pathol., 92, 219, 10.1111/j.1365-2613.2011.00767.x

Gustafsson, 2012, 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, G430, 10.1152/ajpgi.00405.2011

Gutknecht, 2009, Spatio-temporal expression of tryptophan hydroxylase isoforms in murine and human brain: convergent data from Tph2 knockout mice, Eur. Neuropsychopharmacol., 19, 266, 10.1016/j.euroneuro.2008.12.005

Hadjifrangiskou, 2011, A central metabolic circuit controlled by QseC in pathogenic Escherichia coli, Mol. Microbiol., 80, 1516, 10.1111/j.1365-2958.2011.07660.x

Haghikia, 2015, Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine, Immunity, 43, 817, 10.1016/j.immuni.2015.09.007

Han, 2015, Intestinal smooth muscle phenotype determines enteric neuronal survival via GDNF expression, Neuroscience, 290, 357, 10.1016/j.neuroscience.2015.01.056

Hansen, 1999, Transcytosis of immunoglobulin A in the mouse enterocyte occurs through glycolipid raft- and rab17-containing compartments, Gastroenterology, 116, 610, 10.1016/S0016-5085(99)70183-6

Hayes, 2006, Serotonin type-3 receptors mediate cholecystokinin-induced satiation through gastric distension, Am. J. Physiol. Regul. Integr. Comp. Physiol., 291, R115, 10.1152/ajpregu.00002.2006

Heanue, 2006, Expression profiling the developing mammalian enteric nervous system identifies marker and candidate Hirschsprung disease genes, Proc. Natl. Acad. Sci. USA, 103, 6919, 10.1073/pnas.0602152103

Helander, 2014, Surface area of the digestive tract - revisited, Scand. J. Gastroenterol., 49, 681, 10.3109/00365521.2014.898326

Herrera, 2009, Toll-like receptor stimulation differentially regulates vasoactive intestinal peptide type 2 receptor in macrophages, J. Cell. Mol. Med., 13, 3209, 10.1111/j.1582-4934.2008.00662.x

Heuckeroth, 1999, Gene targeting reveals a critical role for neurturin in the development and maintenance of enteric, sensory, and parasympathetic neurons, Neuron, 22, 253, 10.1016/S0896-6273(00)81087-9

Hillsley, 1998, Sensitivity to 5-hydroxytryptamine in different afferent subpopulations within mesenteric nerves supplying the rat jejunum, J. Physiol., 509, 717, 10.1111/j.1469-7793.1998.717bm.x

Hira, 2008, Calcium-sensing receptor mediates phenylalanine-induced cholecystokinin secretion in enteroendocrine STC-1 cells, FEBS J., 275, 4620, 10.1111/j.1742-4658.2008.06604.x

Hoban, 2016, Regulation of prefrontal cortex myelination by the microbiota, Transl. Psychiatry, 6, e774, 10.1038/tp.2016.42

Hooper, 2001, Molecular analysis of commensal host-microbial relationships in the intestine, Science, 291, 881, 10.1126/science.291.5505.881

Howitt, 2016, Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut, Science, 351, 1329, 10.1126/science.aaf1648

Hsiao, 2013, Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders, Cell, 155, 1451, 10.1016/j.cell.2013.11.024

Hurst, 1993, Interleukin-1-Beta Induced Increase in Substance-P in Rat Myenteric Plexus, Gastroenterology, 105, 1754, 10.1016/0016-5085(93)91073-Q

Ibiza, 2016, Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence, Nature, 535, 440, 10.1038/nature18644

Imamura, 1992, Mucosal immune defence mechanisms in enterocolitis complicating Hirschsprung’s disease, Gut, 33, 801, 10.1136/gut.33.6.801

Ishizaka, 1980, Stimulation of phospholipid methylation, Ca2+ influx, and histamine release by bridging of IgE receptors on rat mast cells, Proc. Natl. Acad. Sci. USA, 77, 1903, 10.1073/pnas.77.4.1903

Johansson, 2016, Immunological aspects of intestinal mucus and mucins, Nat. Rev. Immunol., 16, 639, 10.1038/nri.2016.88

Kabouridis, 2015, Microbiota controls the homeostasis of glial cells in the gut lamina propria, Neuron, 85, 289, 10.1016/j.neuron.2014.12.037

Kagnoff, M.F., 1987. Immunology of the digestive system. Physiology of the gastrointestinal tract.

Kalff, 1998, Leukocytes of the intestinal muscularis: their phenotype and isolation, J. Leukoc. Biol., 63, 683, 10.1002/jlb.63.6.683

Karaki, 2006, Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine, Cell Tissue Res., 324, 353, 10.1007/s00441-005-0140-x

Kelly, 2004, Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA, Nat. Immunol., 5, 104, 10.1038/ni1018

Kim, 2013, Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice, Gastroenterology, 145, 396, 10.1053/j.gastro.2013.04.056

King, 2000, UDP-glucuronosyltransferases, Curr. Drug Metab., 1, 143, 10.2174/1389200003339171

Kunze, 2009, Lactobacillus reuteri enhances excitability of colonic AH neurons by inhibiting calcium-dependent potassium channel opening, J. Cell. Mol. Med., 13, 2261, 10.1111/j.1582-4934.2009.00686.x

Le Poul, 2003, Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation, J. Biol. Chem., 278, 25481, 10.1074/jbc.M301403200

Lelievre, 2007, 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, 1688, 10.1016/j.peptides.2007.05.006

Lelouard, 2012, Peyer’s patch dendritic cells sample antigens by extending dendrites through M cell-specific transcellular pores, Gastroenterology, 142, 592, 10.1053/j.gastro.2011.11.039

León-Ponte, 2007, Serotonin provides an accessory signal to enhance T-cell activation by signaling through the 5-HT7 receptor, Blood, 109, 3139, 10.1182/blood-2006-10-052787

Levite, 1998, 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, 12544, 10.1073/pnas.95.21.12544

Ley, 2008, Evolution of mammals and their gut microbes, Science, 320, 1647, 10.1126/science.1155725

Li, 2004, Enteric dopaminergic neurons: definition, developmental lineage, and effects of extrinsic denervation, J. Neurosci., 24, 1330, 10.1523/JNEUROSCI.3982-03.2004

Li, 2010, Altered expression of CD4(+)CD25(+) regulatory T cells and its 5-HT(1a) receptor in patients with major depression disorder, J. Affect. Disord., 124, 68, 10.1016/j.jad.2009.10.018

Liang, 2006, Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides, J. Exp. Med., 203, 2271, 10.1084/jem.20061308

Ligumsky, 1990, Role of interleukin 1 in inflammatory bowel disease--enhanced production during active disease, Gut, 31, 686, 10.1136/gut.31.6.686

Lin, 2013, Submerged fermentation of Lactobacillus rhamnosus YS9 for γ-aminobutyric acid (GABA) production, Braz. J. Microbiol., 44, 183, 10.1590/S1517-83822013000100028

Lindemans, 2015, Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration, Nature, 528, 560, 10.1038/nature16460

Lotz, 1988, Effect of neuropeptides on production of inflammatory cytokines by human monocytes, Science, 241, 1218, 10.1126/science.2457950

Lozupone, 2012, Diversity, stability and resilience of the human gut microbiota, Nature, 489, 220, 10.1038/nature11550

Lv, 2010, CCK mediated the inhibitory effect of oxytocin on the contraction of longitudinal muscle strips of duodenum in male rats, Pflugers Arch., 460, 1063, 10.1007/s00424-010-0880-7

Macpherson, 2000, A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria, Science, 288, 2222, 10.1126/science.288.5474.2222

Madsen, 1999, Lactobacillus species prevents colitis in interleukin 10 gene-deficient mice, Gastroenterology, 116, 1107, 10.1016/S0016-5085(99)70013-2

Mantyh, 1988, 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, 3235, 10.1073/pnas.85.9.3235

Mao, 2013, Bacteroides fragilis polysaccharide A is necessary and sufficient for acute activation of intestinal sensory neurons, Nat. Commun., 4, 1465, 10.1038/ncomms2478

Matsumura, 2005, Possible role of PEPT1 in gastrointestinal hormone secretion, Biochem. Biophys. Res. Commun., 336, 1028, 10.1016/j.bbrc.2005.08.259

Mazmanian, 2005, An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system, Cell, 122, 107, 10.1016/j.cell.2005.05.007

Mazmanian, 2008, A microbial symbiosis factor prevents intestinal inflammatory disease, Nature, 453, 620, 10.1038/nature07008

McDermott, 2006, Immune control of food intake: enteroendocrine cells are regulated by CD4+ T lymphocytes during small intestinal inflammation, Gut, 55, 492, 10.1136/gut.2005.081752

McDole, 2012, Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine, Nature, 483, 345, 10.1038/nature10863

McLean, 2015, Type 3 Muscarinic Receptors Contribute to Clearance of Citrobacter rodentium, Inflamm. Bowel Dis., 21, 1860, 10.1097/MIB.0000000000000408

McLean, 2016, 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, G130, 10.1152/ajpgi.00461.2014

McVey Neufeld, 2013, The microbiome is essential for normal gut intrinsic primary afferent neuron excitability in the mouse, Neurogastroenterol. Motil., 25, 10.1111/nmo.12049

Merchant, 2007, Tales from the crypts: regulatory peptides and cytokines in gastrointestinal homeostasis and disease, J. Clin. Invest., 117, 6, 10.1172/JCI30974

Meredith, 2005, 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, 1187, 10.1096/fj.04-3477fje

Mongardi Fantaguzzi, 2009, Identification of neuron types in the submucosal ganglia of the mouse ileum, Cell Tissue Res., 336, 179, 10.1007/s00441-009-0773-2

Moreira, 2012, Interplay between the QseC and QseE bacterial adrenergic sensor kinases in Salmonella enterica serovar Typhimurium pathogenesis, Infect. Immun., 80, 4344, 10.1128/IAI.00803-12

Moreira, 2016, Bacterial Adrenergic Sensors Regulate Virulence of Enteric Pathogens in the Gut, MBio, 7, 10.1128/mBio.00826-16

Murphy, 2005, New insights into the pathogenesis of Hirschsprung’s associated enterocolitis, Pediatr. Surg. Int., 21, 773, 10.1007/s00383-005-1551-1

Nassif, 1995, Clostridium difficile suppresses colonic vasoactive intestinal peptide associated with altered motility, Mediators Inflamm., 4, 452, 10.1155/S096293519500072X

Neunlist, 1999, Characteristics of mucosally projecting myenteric neurones in the guinea-pig proximal colon, J. Physiol., 517, 533, 10.1111/j.1469-7793.1999.0533t.x

Neunlist, 2003, 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, G1049, 10.1152/ajpgi.00487.2002

Ngu, 1985, Activation of enteric nerve pathways in the guinea-pig duodenum by cholecystokinin octapeptide and pentagastrin, J. Physiol., 364, 31, 10.1113/jphysiol.1985.sp015727

Njoroge, 2012, Enterohemorrhagic Escherichia coli virulence regulation by two bacterial adrenergic kinases, QseC and QseE, Infect. Immun., 80, 688, 10.1128/IAI.05921-11

Nogueira, 1994, Immunocytochemical study of intestinal endocrine cells in germ-free mice, Eur. J. Histochem., 38, 213

Nøhr, 2013, 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, 3552, 10.1210/en.2013-1142

O’Connell, 2006, A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells, Blood, 107, 1010, 10.1182/blood-2005-07-2903

O’Hara, 2006, Consequences of Citrobacter rodentium infection on enteroendocrine cells and the enteric nervous system in the mouse colon, Cell. Microbiol., 8, 646, 10.1111/j.1462-5822.2005.00657.x

Orland, 1954, 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, 147, 10.1177/00220345540330020201

Pácha, 2000, Development of intestinal transport function in mammals, Physiol. Rev., 80, 1633, 10.1152/physrev.2000.80.4.1633

Palazzo, 2007, Activation of enteroendocrine cells via TLRs induces hormone, chemokine, and defensin secretion, J. Immunol., 178, 4296, 10.4049/jimmunol.178.7.4296

Patel, 2012, Differential RET signaling pathways drive development of the enteric lymphoid and nervous systems, Sci. Signal., 5, ra55, 10.1126/scisignal.2002734

Peery, 2012, Burden of gastrointestinal disease in the United States: 2012 update, Gastroenterology, 143, 10.1053/j.gastro.2012.08.002

Perez-Burgos, 2013, Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents, Am. J. Physiol. Gastrointest. Liver Physiol., 304, G211, 10.1152/ajpgi.00128.2012

Psichas, 2015, The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents, Int. J. Obes., 39, 424, 10.1038/ijo.2014.153

Rakhilin, 2016, Simultaneous optical and electrical in vivo analysis of the enteric nervous system, Nat. Commun., 7, 11800, 10.1038/ncomms11800

Rapport, 1948, Serum vasoconstrictor, serotonin; isolation and characterization, J. Biol. Chem., 176, 1243, 10.1016/S0021-9258(18)57137-4

Reigstad, 2015, Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells, FASEB J., 29, 1395, 10.1096/fj.14-259598

Reimann, 2012, G-protein-coupled receptors in intestinal chemosensation, Cell Metab., 15, 421, 10.1016/j.cmet.2011.12.019

Rescigno, 2001, Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria, Nat. Immunol., 2, 361, 10.1038/86373

Reyniers, 1932, The use of germ-free guinea pigs in bacteriology, Proc. Ind. Acad. Sci., 42, 35

Rosas-Ballina, 2008, Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia, Proc. Natl. Acad. Sci. USA, 105, 11008, 10.1073/pnas.0803237105

Rosas-Ballina, 2011, Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit, Science, 334, 98, 10.1126/science.1209985

Round, 2010, Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota, Proc. Natl. Acad. Sci. USA, 107, 12204, 10.1073/pnas.0909122107

Rubin, 2000, Altered enteroendocrine cell expression in T cell receptor alpha chain knock-out mice, Microsc. Res. Tech., 51, 112, 10.1002/1097-0029(20001015)51:2<112::AID-JEMT2>3.0.CO;2-D

Rudd, 2005, Peritoneal macrophages express the serotonin transporter, J. Neuroimmunol., 159, 113, 10.1016/j.jneuroim.2004.10.013

Rühl, 2001, IL-1β and IL-10 have dual effects on enteric glial cell proliferation, Neurogastroenterol. Motil., 13, 89, 10.1046/j.1365-2982.2001.00245.x

Sampson, 2016, Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease, Cell, 167, 1469, 10.1016/j.cell.2016.11.018

Samuel, 2008, 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, 16767, 10.1073/pnas.0808567105

Sánchez, 1996, Renal agenesis and the absence of enteric neurons in mice lacking GDNF, Nature, 382, 70, 10.1038/382070a0

Satoh, 1988, Atropine inhibits the degranulation of Paneth cells in ex-germ-free mice, Cell Tissue Res., 253, 397, 10.1007/BF00222296

Satoh, 1986, Quantitative light microscopic observations on Paneth cells of germ-free and ex-germ-free Wistar rats, Digestion, 34, 115, 10.1159/000199319

Satoh, 1992, Bethanechol and a G-protein activator, NaF/AlCl3, induce secretory response in Paneth cells of mouse intestine, Cell Tissue Res., 269, 213, 10.1007/BF00319611

Schäfer, 1999, 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, 527, 10.1089/107999099313974

Schéle, 2013, 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, 3643, 10.1210/en.2012-2151

Scheller, 2011, The pro- and anti-inflammatory properties of the cytokine interleukin-6, Biochim. Biophys. Acta, 1813, 878, 10.1016/j.bbamcr.2011.01.034

Schuchardt, 1994, Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret, Nature, 367, 380, 10.1038/367380a0

Sender, 2016, Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans, Cell, 164, 337, 10.1016/j.cell.2016.01.013

Serafini, 2015, Transcriptional regulation of innate lymphoid cell fate, Nat. Rev. Immunol., 15, 415, 10.1038/nri3855

Shajib, 2015, The role of serotonin and its receptors in activation of immune responses and inflammation, Acta Physiol. (Oxf.), 213, 561, 10.1111/apha.12430

Singh, 2014, Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis, Immunity, 40, 128, 10.1016/j.immuni.2013.12.007

Siragusa, 2007, Synthesis of gamma-aminobutyric acid by lactic acid bacteria isolated from a variety of Italian cheeses, Appl. Environ. Microbiol., 73, 7283, 10.1128/AEM.01064-07

Smith, 2013, The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis, Science, 341, 569, 10.1126/science.1241165

Song, 2015, 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, 236, 10.5056/jnm14095

Sonnenberg, 2011, CD4(+) lymphoid tissue-inducer cells promote innate immunity in the gut, Immunity, 34, 122, 10.1016/j.immuni.2010.12.009

Soret, 2010, Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats, Gastroenterology, 138, 1772, 10.1053/j.gastro.2010.01.053

Stadnyk, 1996, Pattern of proinflammatory cytokine mRNA expression during Trichinella spiralis infection of the rat, Infect. Immun., 64, 5138, 10.1128/iai.64.12.5138-5143.1996

Stanisz, 1986, 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, 152, 10.4049/jimmunol.136.1.152

Starke-Buzetti, 2008, Increased glial-derived neurotrophic factor in the small intestine of rats infected with the tapeworm, Hymenolepis diminuta, Int. J. Exp. Pathol., 89, 458, 10.1111/j.1365-2613.2008.00606.x

Starodub, 2000, Histamine suppresses A-type potassium current in myenteric neurons from guinea pig small intestine, J. Pharmacol. Exp. Ther., 294, 555

Stefulj, 2000, mRNA expression of serotonin receptors in cells of the immune tissues of the rat, Brain Behav. Immun., 14, 219, 10.1006/brbi.1999.0579

Sternini, 2008, Enteroendocrine cells: a site of ‘taste’ in gastrointestinal chemosensing, Curr. Opin. Endocrinol. Diabetes Obes., 15, 73, 10.1097/MED.0b013e3282f43a73

Sugimoto, 2008, IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis, J. Clin. Invest., 118, 534

Sun, 2000, Vasoactive intestinal peptide (VIP) inhibits TGF-β1 production in murine macrophages, J. Neuroimmunol., 107, 88, 10.1016/S0165-5728(00)00245-9

Tazoe, 2008, Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions, J. Physiol. Pharmacol., 59, 251

Thangaraju, 2009, GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon, Cancer Res., 69, 2826, 10.1158/0008-5472.CAN-08-4466

Theoharides, 1982, Differential release of serotonin and histamine from mast cells, Nature, 297, 229, 10.1038/297229a0

Vaishnava, 2011, The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine, Science, 334, 255, 10.1126/science.1209791

Valeur, 2004, Colonization and immunomodulation by Lactobacillus reuteri ATCC 55730 in the human gastrointestinal tract, Appl. Environ. Microbiol., 70, 1176, 10.1128/AEM.70.2.1176-1181.2004

Vallance, 1997, Increased intestinal muscle contractility and worm expulsion in nematode-infected mice, Am. J. Physiol., 272, G321

van der Waaij, 1971, Colonization resistance of the digestive tract in conventional and antibiotic-treated mice, J. Hyg. (Lond.), 69, 405, 10.1017/S0022172400021653

van der Waaij, 1996, In vivo IgA coating of anaerobic bacteria in human faeces, Gut, 38, 348, 10.1136/gut.38.3.348

Veiga-Fernandes, 2007, Tyrosine kinase receptor RET is a key regulator of Peyer’s patch organogenesis, Nature, 446, 547, 10.1038/nature05597

von Boyen, 2011, Distribution of enteric glia and GDNF during gut inflammation, BMC Gastroenterol., 11, 3, 10.1186/1471-230X-11-3

Vulchanova, 2007, Anatomical evidence for enteric neuroimmune interactions in Peyer’s patches, J. Neuroimmunol., 185, 64, 10.1016/j.jneuroim.2007.01.014

Wang, 2003, Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation, Nature, 421, 384, 10.1038/nature01339

Wang, 2014, Regulatory T cells promote a protective Th17-associated immune response to intestinal bacterial infection with C. rodentium, Mucosal Immunol., 7, 1290, 10.1038/mi.2014.17

Wheway, 2005, A fundamental bimodal role for neuropeptide Y1 receptor in the immune system, J. Exp. Med., 202, 1527, 10.1084/jem.20051971

Wolin, 1981, Fermentation in the rumen and human large intestine, Science, 213, 1463, 10.1126/science.7280665

Wright, 1979, Trichinella spiralis: an intracellular parasite in the intestinal phase, J. Parasitol., 65, 441, 10.2307/3280292

Xavier, 2007, Unravelling the pathogenesis of inflammatory bowel disease, Nature, 448, 427, 10.1038/nature06005

Xia, 1999, IL-1β and IL-6 excite neurons and suppress nicotinic and noradrenergic neurotransmission in guinea pig enteric nervous system, J. Clin. Invest., 103, 1309, 10.1172/JCI5823

Yamasaki, 1983, Modulation by alpha 2-adrenergic stimulation of IgE-mediated 14C-serotonin release from rat mast cells, Agents Actions, 13, 310, 10.1007/BF01971482

Yano, 2015, Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis, Cell, 161, 264, 10.1016/j.cell.2015.02.047

Yissachar, 2017, An Intestinal Organ Culture System Uncovers a Role for the Nervous System in Microbe-Immune Crosstalk, Cell, 168, 1135, 10.1016/j.cell.2017.02.009

Zhao, 2003, 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, 948, 10.4049/jimmunol.171.2.948

Zheng, 2008, Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens, Nat. Med., 14, 282, 10.1038/nm1720