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The distribution and chemical coding of enteroendocrine cells in Trypanosoma cruzi-infected individuals with chagasic megacolon

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Abstract

Chagas disease is caused by the parasite, Trypanosoma cruzi that causes chronic cardiac and digestive dysfunction. Megacolon, an irreversible dilation of the left colon, is the main feature of the gastrointestinal form of Chagas disease. Patients have severe constipation, a consequence of enteric neuron degeneration associated with chronic inflammation. Dysmotility, infection, neuronal loss and a chronic exacerbated inflammation, all observed in Chagas disease, can affect enteroendocrine cells (EEC) expression, which in turn, could influence the inflammatory process. In this study, we investigated the distribution and chemical coding of EEC in the dilated and non-dilated portion of T. cruzi-induced megacolon and in non-infected individuals (control colon). Using immunohistochemistry, EECs were identified by applying antibodies to chromogranin A (CgA), glucagon-like peptide 1 (GLP-1), 5-hydroxytryptamine (5-HT), peptide YY (PYY) and somatostatin (SST). Greater numbers of EEC expressing GLP-1 and SST occurred in the dilated portion compared to the non-dilated portion of the same patients with Chagas disease and in control colon, but numbers of 5-HT and PYY EEC were not significantly different. However, it was noticeable that EEC in which 5-HT and PYY were co-expressed were common in control colon, but were rare in the non-dilated and absent in the dilated portion of chagasic megacolon. An increase in the number of CgA immunoreactive EEC in chagasic patients reflected the increases in EEC numbers summarised above. Our data suggests that the denervation and associated chronic inflammation are accompanied by changes in the number and coding of EEC that could contribute to disorders of motility and defence in the chagasic megacolon.

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References

  • Adad SJ, Cancado CG, Etchebehere RM, Teixeira VP, Gomes UA, Chapadeiro E, Lopes ER (2001) Neuron count reevaluation in the myenteric plexus of chagasic megacolon after morphometric neuron analysis. Virchows Arch 438:254–258. https://doi.org/10.1007/s004280000319

    Article  CAS  PubMed  Google Scholar 

  • Agersnap M, Rehfeld JF (2014) Measurement of nonsulfated cholecystokinins. Scand J Clin Lab Investig 74(5):424–431

    CAS  Google Scholar 

  • Ahern GP (2011) 5-HT and the immune system. Current Opinion in Pharmacology 11:29–33

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bafutto M, Luquetti AO, Neto SG, Penhavel FAS, Oliveira EC (2017) Constipation is related to small bowel disturbance rather than colonic enlargement in acquired chagasic megacolon. Gastroenterol Res 10:213. https://doi.org/10.14740/gr872w

    Article  Google Scholar 

  • Baldassano S, Wang G-D, Mulè F, Wood JD (2012) Glucagon-like peptide-1 modulates neurally evoked mucosal chloride secretion in guinea pig small intestine in vitro. Am J Physiol-Gastrointestinal Liv Physiol 302:G352–G358

    CAS  Google Scholar 

  • Benchimol Barbosa PR (2006) The oral transmission of Chagas’ disease: an acute form of infection responsible for regional outbreaks. Int J Cardiol 112:132–133. https://doi.org/10.1016/j.ijcard.2005.11.087

    Article  PubMed  Google Scholar 

  • Bermudez R, Vigliano F, Quiroga MI, Nieto JM, Bosi G, Domeneghini C (2007) Immunohistochemical study on the neuroendocrine system of the digestive tract of turbot, Scophthalmus maximus (L.), infected by Enteromyxum scophthalmi (Myxozoa). Fish Shellfish Immunol 22:252–263. https://doi.org/10.1016/j.fsi.2006.05.006

    Article  CAS  PubMed  Google Scholar 

  • Bern C (2015) Chagas’ disease New England. J Med 373:456–466

    CAS  Google Scholar 

  • Bern C et al (2007) Evaluation and treatment of chagas disease in the United States: a systematic review. JAMA 298:2171–2181. https://doi.org/10.1001/jama.298.18.2171

    Article  CAS  PubMed  Google Scholar 

  • Brubaker PL, Drucker DJ, Asa SL, Swallow C, Redston M, Greenberg GR (2002) Prolonged gastrointestinal transit in a patient with a glucagon-like peptide (GLP)-1-and-2-producing neuroendocrine tumor. J Clin Endocrinol Metab 87:3078–3083

    CAS  PubMed  Google Scholar 

  • Chisholm C, Greenberg GR (2002) Somatostatin-28 regulates GLP-1 secretion via somatostatin receptor subtype 5 in rat intestinal cultures. Am J Physiol-Endocrinol Metab 283:E311–E317

    CAS  PubMed  Google Scholar 

  • Cho H-J, Callaghan B, Bron R, Bravo DM, Furness JB (2014) Identification of enteroendocrine cells that express TRPA1 channels in the mouse intestine. Cell Tissue Res 356(1):77–82

    CAS  PubMed  Google Scholar 

  • Cho H-J, Kosari S, Hunne B, Callaghan B, Rivera LR, Bravo DM, Furness JB (2015) Differences inhormone localisation patterns of K and L type enteroendocrine cells in the mouse andpig small intestine and colon. Cell Tissue Res 359(2):693–698

    CAS  PubMed  Google Scholar 

  • Chowers Y, Cahalon L, Lahav M, Schor H, Tal R, Bar-Meir S, Levite M (2000) Somatostatin through its specific receptor inhibits spontaneous and TNF-α-and bacteria-induced IL-8 and IL-1β secretion from intestinal epithelial cells. J Immunol 165:2955–2961

    CAS  PubMed  Google Scholar 

  • Coates MD et al (2004) Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology 126:1657–1664

    CAS  PubMed  Google Scholar 

  • Coleman NS et al (2006) Abnormalities of serotonin metabolism and their relation to symptoms in untreated celiac disease. Clin Gastroenterol Hepatol 4:874–881

    CAS  PubMed  Google Scholar 

  • Costedio MM, Coates MD, Danielson AB, Buttolph TR, Blaszyk HJ, Mawe GM, Hyman NH (2008) Serotonin signaling in diverticular disease. J Gastrointestinal Surg 12:1439

    Google Scholar 

  • da Silveira AB et al (2007a) Neurochemical coding of the enteric nervous system in chagasic patients with megacolon. Dig Dis Sci 52:2877–2883. https://doi.org/10.1007/s10620-006-9680-5

    Article  PubMed  Google Scholar 

  • da Silveira AB, Lemos EM, Adad SJ, Correa-Oliveira R, Furness JB, D’Avila Reis D (2007b) Megacolon in Chagas disease: a study of inflammatory cells, enteric nerves, and glial cells. Hum Pathol 38:1256–1264. https://doi.org/10.1016/j.humpath.2007.01.020

    Article  PubMed  Google Scholar 

  • de Freitas M, de Oliveira E, de Oliveira F, Jabari S, Brehmer A, da Silveira A (2015) Is the increased presence of CD 8 T-lymphocytes related to serotonin levels in C hagas disease? Colorectal Dis 17:268–269

    PubMed  Google Scholar 

  • De Jonge F et al (2003) Effects of Schistosoma mansoni infection on somatostatin and somatostatin receptor 2A expression in mouse ileum. Neurogastroenterol Motil 15:149–159. https://doi.org/10.1046/j.1365-2982.2003.00400.x

    Article  PubMed  Google Scholar 

  • de Oliveira JA, Freitas MAR, de Oliveira EC, Jabari S, Brehmer A, da Silveira ABM (2019) 5-HT3A serotonin receptor in the gastrointestinal tract: the link between immune system and enteric nervous system in the digestive form of Chagas disease. Parasitol Res 118:1325–1329. https://doi.org/10.1007/s00436-019-06241-w

    Article  PubMed  Google Scholar 

  • Di Sabatino A et al (2014) Increase in neuroendocrine cells in the duodenal mucosa of patients with refractory celiac disease. Am J Gastroenterol 109:258–269

    PubMed  Google Scholar 

  • Dias JC, Silveira AC, Schofield CJ (2002) The impact of Chagas disease control in Latin America: a review. Mem Inst Oswaldo Cruz 97:603–612. https://doi.org/10.1590/s0074-02762002000500002

    Article  CAS  PubMed  Google Scholar 

  • Duhamel B (1956) Une nouvelle operation pour le megacôlon congenital: L’abaissement retrocecal et trans-anal du côlon et son application posible au traitement de quelques malformations. Press Med 95:2249–2250

    Google Scholar 

  • El-Salhy M, Gundersen D (2015) Diet in irritable bowel syndrome. Nutr J 14:36. https://doi.org/10.1186/s12937-015-0022-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • El-Salhy M, Gundersen D, Østgaard H, Lomholt-Beck B, Hatlebakk JG, Hausken T (2012) Low densities of serotonin and peptide YY cells in the colon of patients with irritable bowel syndrome. Dig Dis Sci 57:873–878

    CAS  PubMed  Google Scholar 

  • Everard A, Cani PD (2014) Gut microbiota and GLP-1. Reviews in Endocrine and Metabolic Disorders 15:189–196

    CAS  PubMed  Google Scholar 

  • Facer P, Bishop AE, Lloyd RV, Wilson BS, Hennessy RJ, Polak JM (1985) Chromogranin: a newly recognized marker for endocrine cells of the human gastrointestinal tract. Gastroenterology 89:1366–1373. https://doi.org/10.1016/0016-5085(85)90657-2

    Article  CAS  PubMed  Google Scholar 

  • Freitas M, Segatto N, Tischler N, de Oliveira E, Brehmer A, da Silveira A (2017) Relation between mast cells concentration and serotonin expression in chagasic megacolon development. Parasite Immunol 39:e12414. https://doi.org/10.1111/pim.12414

    Article  CAS  Google Scholar 

  • Furness JB, Rivera LR, Cho H-J, Bravo DM, Callaghan B (2013) The Gut as a Sensory Organ Nature reviews. Gastroenterol Hepatol 10:729. https://doi.org/10.1038/nrgastro.2013.180

    Article  CAS  Google Scholar 

  • Gattuso J, Kamm M, Talbot I (1997) Pathology of idiopathic megarectum and megacolon. Gut 41:252–257

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gershon MD (2013) 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr Opin Endocrinol Diabetes Obes 20:14

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hansen L, Hartmann B, Bisgaard T, Mineo H, Jørgensen PN, Holst JJ (2000) Somatostatin restrains the secretion of glucagon-like peptide-1 and-2 from isolated perfused porcine ileum. Am J Physiol-Endocrinol Metab 278:E1010–E1018

    CAS  PubMed  Google Scholar 

  • Harrison E, Lal S, McLaughlin JT (2013) Enteroendocrine cells in gastrointestinal pathophysiology. Curr Opin Pharmacol 13:941–945. https://doi.org/10.1016/j.coph.2013.09.012

    Article  CAS  PubMed  Google Scholar 

  • Helyes Z et al (2001) Anti-inflammatory effect of synthetic somatostatin analogues in the rat. Br J Pharmacol 134:1571–1579

    CAS  PubMed  PubMed Central  Google Scholar 

  • Husted AS, Trauelsen M, Rudenko O, Hjorth SA, Schwartz TW (2017) GPCR-mediated signaling of metabolites. Cell Metab 25:777–796. https://doi.org/10.1016/j.cmet.2017.03.008

    Article  CAS  PubMed  Google Scholar 

  • Jabari S, da Silveira AB, de Oliveira EC, Neto SG, Quint K, Neuhuber W, Brehmer A (2011) Partial, selective survival of nitrergic neurons in chagasic megacolon. Histochem Cell Biol 135:47–57

    CAS  PubMed  Google Scholar 

  • Jabari S, da Silveira A, de Oliveira E, Quint K, Wirries A, Neuhuber W, Brehmer A (2013) Interstitial cells of C ajal: crucial for the development of megacolon in human C hagas’ disease? Colorectal Dis 15:e592–e598

    CAS  PubMed  Google Scholar 

  • Jabari S, da Silveira AB, de Oliveira EC, Quint K, Wirries A, Neuhuber W, Brehmer A (2014a) Mucosal layers and related nerve fibres in non-chagasic and chagasic human colon–a quantitative immunohistochemical study. Cell Tissue Res 358:75–83. https://doi.org/10.1007/s00441-014-1934-5

    Article  CAS  PubMed  Google Scholar 

  • Jabari S, de Oliveira EC, Brehmer A, da Silveira AB (2014b) Chagasic megacolon: enteric neurons and related structures. Histochem Cell Biol 142:235–244

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kovacs T, Walsh J, Maxwell V, Wong H, Azuma T, Katt E (1989) Gastrin is a major mediator of the gastric phase of acid secretion in dogs: proof by monoclonal antibody neutralization. Gastroenterology 97(6):1406–1413

    CAS  PubMed  Google Scholar 

  • Kannen V et al (2018) Mast cells and serotonin synthesis modulate Chagas disease in the colon: clinical and experimental evidence. Dig Dis Sci 63:1473–1484

    CAS  PubMed  Google Scholar 

  • Köberle F (1968) Chagas' Disease and Chagas' syndromes: the pathology of American trypanosomiasis. In: Advances in parasitology, vol 6. Elsevier, pp 63–116. https://doi.org/https://doi.org/10.1016/S0065-308X(08)60472-8

  • Latorre R, Sternini C, De Giorgio R, Greenwood-Van Meerveld B (2016) Enteroendocrine cells: a review of their role in brain-gut communication. Neurogastroenterol Motil 28:620–630. https://doi.org/10.1111/nmo.12754

    Article  CAS  PubMed  Google Scholar 

  • Leventhal A, Gimmon Z (1978) Toxic idiopathic megacolon: fatal outcome in a mentally retarded adolescent. Dis Colon Rectum 21:383–386

    CAS  PubMed  Google Scholar 

  • Lincoln J, Crowe R, Kamm M, Burnstock G, Lennard-Jones J (1990) Serotonin and 5-hydroxyindoleacetic acid are increased in the sigmoid colon in severe idiopathic constipation. Gastroenterology 98:1219–1225

    CAS  PubMed  Google Scholar 

  • Lindop G (1983) Enterochromaffin cell hyperplasia and megacolon: report of a case. Gut 24:575–578

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lopes ER, Rocha A, Meneses AC, Lopes MA, Fatureto MC Lopes GP, Chapadeiro E (1989) Prevalence of visceromegalies in necropsies carried out in Triangulo Mineiro from 1954 to 1988. Rev Soc Bras Med Trop 22:211–215. https://doi.org/10.1590/s0037-86821989000400008

    Article  CAS  PubMed  Google Scholar 

  • Lund ML, Egerod KL, Engelstoft MS, Dmytriyeva O, Theodorsson E, Patel BA, Schwartz TW (2018) Enterochromaffin 5-HT cells—a major target for GLP-1 and gut microbial metabolites. Mol Metab 11:70–83. https://doi.org/10.1016/j.molmet.2018.03.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maniero VC et al (2007) IFNG? 874T/A polymorphism is not associated with American tegumentary leishmaniasis susceptibility but can influence Leishmania induced IFN-gamma production. BMC Infect Dis 7:33 Misch. https://doi.org/10.1186/1471-2334-7-33

  • Martins P et al (2017) Analysis of enteroendocrine cell populations in the human colon. Cell Tissue Res 367:161–168. https://doi.org/10.1007/s00441-016-2530-7

    Article  CAS  PubMed  Google Scholar 

  • Martins PR, Nascimento RD, dos Santos AT, de Oliveira EC, Martinelli PM (2018) Reis DdA Mast cell-nerve interaction in the colon of Trypanosoma cruzi-infected individuals with chagasic megacolon. Parasitol Res 117:1147–1158

    PubMed  Google Scholar 

  • Martins PR et al (2015) Mast cells in the colon of Trypanosoma cruzi-infected patients: are they involved in the recruitment, survival and/or activation of eosinophils? Parasitol Res 114:1847–1856

    PubMed  Google Scholar 

  • McCall L-I, Tripathi A, Vargas F, Knight R, Dorrestein PC, Siqueira-Neto JL (2018) Experimental Chagas disease-induced perturbations of the fecal microbiome and metabolome. PLoS Neglected Tropical Dis 12:e0006344

    Google Scholar 

  • Meier-Ruge WA, Müller-Lobeck H, Stoss F, Bruder E (2006) The pathogenesis of idiopathic megacolon. European J Gastroenterol Hepatol 18:1209–1215

    CAS  Google Scholar 

  • Meneghelli UG, Macedo J, Troncon L, Dantas R (1982) Basal motility of dilated and non-dilated sigmoid colon and rectum in Chagas’ disease. Arquivos de Gastroenterol 19:127–132

    CAS  Google Scholar 

  • Neurauter G, Schrocksnadel K, Scholl-Burgi S, Sperner-Unterweger B, Schubert C, Ledochowski M, Fuchs D (2008) Chronic immune stimulation correlates with reduced phenylalanine turnover. Curr Drug Metab 9:622–627

    CAS  PubMed  Google Scholar 

  • Ng QX, Soh AYS, Loke W, Lim DY, Yeo WS (2018) The role of inflammation in irritable bowel syndrome (IBS). J Inflamm Res 11:345–349. https://doi.org/10.2147/JIR.S174982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohkusa T, Koido S, Nishikawa Y, Sato N (2019) Gut microbiota and chronic constipation: a review and update. Frontiers in medicine 6. https://doi.org/10.3389/fmed.2019.00019

  • Oxenkrug G (2011) Interferon-gamma—inducible inflammation: contribution to aging and aging-associated psychiatric disorders. Aging Dis 2:474–486

    PubMed  PubMed Central  Google Scholar 

  • Patterson M, Murphy KG, le Roux CW, Ghatei MA, Bloom SR (2005) Characterization of ghrelinlikeimmunoreactivity in human plasma. J Clin Endocrinol Metabolism 90(4):2205–2211

    CAS  Google Scholar 

  • Peeters T, Janssens J, Vantrappen G (1983) Somatostatin and the interdigestive migrating motor complex in man. Regul Pept 5:209–217

    CAS  PubMed  Google Scholar 

  • Perez-Ayala A, Perez-Molina JA, Norman F, Monge-Maillo B, Faro MV, Lopez-Velez R (2011) Gastro-intestinal Chagas disease in migrants to Spain: prevalence and methods for early diagnosis. Ann Trop Med Parasitol 105:25–29. https://doi.org/10.1179/136485910X12851868780423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pinto J-J et al (2019) Characterization of digestive disorders of patients with chronic Chagas disease in Cochabamba, Bolivia. Heliyon 5:e01206

    PubMed  PubMed Central  Google Scholar 

  • Raybould HE (2010) Gut chemosensing: interactions between gut endocrine cells and visceral afferents. Autonomic Neuroscience 153:41–46

    CAS  PubMed  Google Scholar 

  • Rehfeld JF (1998) Accurate measurement of cholecystokinin in plasma. Clin Chem 44(5):991–1001

    CAS  PubMed  Google Scholar 

  • Ribeiro U Jr, Safatle-Ribeiro AV, Habr-Gama A, Gama-Rodrigues JJ, Sohn J, Reynolds JC (1998) Effect of Chagas’ disease on nitric oxide-containing neurons in severely affected and unaffected intestine. Dis Colon Rectum 41:1411–1417. https://doi.org/10.1007/bf02237058

    Article  PubMed  Google Scholar 

  • Robello C et al (2019) The fecal, oral, and skin microbiota of children with Chagas disease treated with benznidazole. PLoS one. https://doi.org/10.1371/journal.pone.0212593

    Article  PubMed  PubMed Central  Google Scholar 

  • Rogawski MA, Goodrich J, Gershon M, Touloukian R (1978) Hirschsprung’s disease: absence of serotonergic neurons in the aganglionic colon. J Pediatr Surg 13:608–615

    CAS  PubMed  Google Scholar 

  • Rowlands J, Heng J, Newsholme P, Carlessi R (2018) Pleiotropic effects of GLP-1 and analogs on cell signaling, metabolism, and function. Front Endocrinol 9 doi:https://doi.org/10.3389/fendo.2018.00672

  • Santos S, Barcelos I, Mesquita M (2000) Total and segmental colonic transit time in constipated patients with Chagas disease without megaesophagus or megacolon. Braz J Med Biol Res 33:43–49

    CAS  PubMed  Google Scholar 

  • Sei Y et al (2018) Mature enteroendocrine cells contribute to basal and pathological stem cell dynamics in the small intestine. Am J Physiol Gastrointest Liver Physiol 315:G495–g510. https://doi.org/10.1152/ajpgi.00036.2018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shulkes A, Fletcher D, Hardy K (1983) Organ and plasma metabolism of neurotensin in sheep. Am J Physiol Endocrinol Metab 245(5):E457–E462

    CAS  Google Scholar 

  • Soeda J, O’Briain DS, Puri P (1993) Regional reduction in intestinal neuroendocrine cell populations in enterocolitis complicating Hirschsprung’s disease. J Pediatr Surg 28:1063–1068

    CAS  PubMed  Google Scholar 

  • Spiller R, Jenkins D, Thornley J, Hebden J, Wright T, Skinner M, Neal K (2000) Increased rectal mucosal enteroendocrine cells T lymphocytes, and increased gut permeability following acutecampylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut 47:804–811. https://doi.org/10.1136/gut.47.6.804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stoyanova II, Gulubova MV (2002) Mast cells and inflammatory mediators in chronic ulcerative colitis. Acta Histochem 104:185–192. https://doi.org/10.1078/0065-1281-00641

    Article  CAS  PubMed  Google Scholar 

  • Tolessa T, Gutniak M, Holst JJ, Efendic S, Hellström PM (1998) Inhibitory effect of glucagon-like peptide-1 on small bowel motility. Fasting but not fed motility inhibited via nitric oxide independently of insulin and somatostatin. J Clin Invest 102:764–774

    CAS  PubMed  PubMed Central  Google Scholar 

  • Torres OA, Calzada JE, Beraún Y, Morillo CA, González A, González CI, Martín J (2010) Role of the IFNG+ 874T/A polymorphism in Chagas disease in a Colombian population Infection. Genet Evol 10:682–685. https://doi.org/10.1016/j.meegid.2010.03.009

    Article  CAS  Google Scholar 

  • Van Der Wielen N et al (2014) Cross-species comparison of genes related to nutrient sensing mechanisms expressed along the intestine. PLoS One 9:e107531

    PubMed  PubMed Central  Google Scholar 

  • Vezzadini C, Toni R, Vezzadini P (1996) Pancreatic somatostatinoma presenting with chronic intestinal pseudo-obstruction syndrome. Minerva Gastroenterol e Dietol 42:227–231

    CAS  Google Scholar 

  • Voss U, Sand E, Hellström PM, Ekblad E (2012) Glucagon-like peptides 1 and 2 and vasoactive intestinal peptide are neuroprotective on cultured and mast cell co-cultured rat myenteric neurons. BMC gastroenterology 12:30

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang R et al (2018) Gut microbiota play an essential role in the antidiabetic effects of rhein. Evid Based Complement Alternat Med 2018:609328. https://doi.org/10.1155/2018/6093282

    Article  Google Scholar 

  • Worthington JJ, Reimann F, Gribble F (2018) Enteroendocrine cells-sensory sentinels of the intestinal environment and orchestrators of mucosal immunity. Mucosal Immunol 11:3–20

    CAS  PubMed  Google Scholar 

  • Yanaihara N, Yanaihara C, Nagai K, Sato H, Shimizu F, Yamaguchi K, Abe K (1980) Motilin-like immunoreactivity in porcine, canine, human and rat tissues. Biomedical Research 1(1):76–83

    CAS  Google Scholar 

  • Yusta B et al (2015) GLP-1R agonists modulate enteric immune responses through the intestinal intraepithelial lymphocyte GLP-1R. Diabetes 64:2537–2549

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This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

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Martins, P.R., Fakhry, J., de Oliveira, A.J. et al. The distribution and chemical coding of enteroendocrine cells in Trypanosoma cruzi-infected individuals with chagasic megacolon. Histochem Cell Biol 155, 451–462 (2021). https://doi.org/10.1007/s00418-020-01947-w

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