Glutamine Supplementation Effects on Reducing Inflammation in The Ileum of Acute and Chronic Diarrhea Rats Induced by Enteropathogenic Escherichia coli

Deddy Satriya Putra, Fadil Oenzil, Eryati Darwin, Hafni Bachtiar, Tofrizal Tofrizal


BACKGROUND: Glutamine, a non-essential amino acid, is the main fuel in the gastrointestinal mucosa. It is thought to protect the intestinal mucosa against local or systemic injury from diarrhea. This study aimed to determine the relationship between glutamine supplementation and ileum histopathology in acute and chronic diarrhea rats induced by enteropathogenic Escherichia coli (EPEC).

METHODS: A randomized post-test only control group design was conducted. Thirty Rattus norvegicus Wistar strain were divided into 5 groups: one negative control group, two acute, and two chronic diarrhea groups. All four diarrhea groups were induced by EPEC at a dose of 108 CFU/mL. One acute and one chronic groups were supplemented with glutamine at a dose of 810 mg/200 g body weight for 14 days. While the other two diarrhea groups were not treated. The intestinal histopathology of each group was assessed and the level of inflammation was classified.

RESULTS: Significant differences in inflammation levels were found among the groups (p<0.05). The highest inflammation level was observed in the acute diarrhea group without glutamine supplementation. Inflammation levels of both acute and chronic diarrhea with glutamine supplementation groups were significantly lower than the inflammation levels of acute and chronic diarrhea without glutamine supplementation groups.

CONCLUSION: Supplementation of glutamine reduces the level of inflammation and leads to the histopathological improvement of the rat’s ileum.

KEYWORDS: enteropathogenic Escherichia coli, glutamine, gastrointestinal tract, histopathology, ileum

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Soedarmo SSP, Garna H, Hadinegoro SRS. Buku ajar ilmu kesehatan anak: Infeksi dan penyakit tropis [Child health science textbooks: Infections and tropical diseases]. Jakarta: Ikatan Dokter Anak Indonesia; 2003.

Randy PP, Russell WS [Internet]. Pediatric: General medicine [update 2018 Nov 26; cited 2019 May 26]. Available from:

Komarulzaman A, Smits J, de Jong E. Clean water, sanitation and diarrhoea in Indonesia: Effects of household and community factors. Glob. Public Health. 2017; 12: 1141-55, CrossRef.

Dinas Kesehatan Provinsi Riau. Profil Kesehatan Provinsi Riau 2012. Pekanbaru: Dinas Kesehatan Provinsi Riau; 2012, article.

Behiry I, Abada E, Ahmed E, Labeeb R. Enteropathogenic Escherichia coli associated with diarrhea in children in Cairo, Egypt. Sci World J. 2011; 11: 2613-19, CrossRef.

Ochoa TJ, Contreras CA. Enteropathogenic E. coli (EPEC) infection in children. Curr Opin Infect Dis. 2011; 24: 478-83, CrossRef.

Amin LZ. Tatalaksana diare akut [Management of acute diarrhea]. Cermin Dunia Kedokretan. 2015; 230: 504-7, article.

Sullivan P, Marsh MN. Small intestinal mucosal histology in the syndrome of persistent diarrhoea and malnutrition: A review. Acta Paediatr Suppl. 1992; 381: 72-7, CrossRef.

Towoliu S, Lintong P, Kairupan C. Pengaruh pemberian lactobacillus terhadap gambaran mikroskopis mukosa usus halus tikus wistar (Rattus norvegicus) yang diinfeksi dengan Escherichia coli [The effect of lactobacillus on the microscopic picture of the small intestine mucosa of the wistar rat (Rattus norvegicus) infected with Escherichia coli]. Jurnal e-Biomedik (eBM). 2013; 1: 930-9, CrossRef.

Duggan C, Gannon J, Walker WA. Protective nutrients and functional foods for the gastrointestinal tract. Am J Clin Nutr. 2002; 75: 789-808, CrossRef.

Carneiro-Filho BA, Bushen OY, Brito GA, Lima AA, Guerrant RL. Glutamine analogues as adjunctive therapy for infectious diarrhea. Curr Infect Dis Rep. 2003; 5: 114-9, CrossRef.

Vicario M, Amat C, Rivero M, Moretó M, Pelegrí C. Dietary glutamine affects mucosal functions in rats with mild DSS-induced colitis. J Nutr. 2007; 137: 1931-7, CrossRef.

Rao R, Samak G. Role of glutamine in protection of intestinal epithelial tight junctions. J Epithel Biol Pharmacol. 2012; 5: 47-54, CrossRef.

Xue H, Sawyer B, Field C, Dieleman LA, Murray D, Baracos VE. Bolus oral glutamine protects rats against CPT-11-induced diarrhea and differentially activates cytoprotective mechanisms in host intestine but not tumor. J Nutr. 2008; 138: 740-6, CrossRef.

Kim MH, Kim H. The roles of glutamine in the intestine and its implication in intestinal diseases. Int J Mol Sci. 2017; 18: E1051, CrossRef.

Irawan R, Subijanto MS, Putra S, Soetjipto. Efek pemberian glutamin terhadap aktivitas sucrase, maltase, lactase dan ekspresi spectrin, clathrin dalam perbaikan mikrovili ileum pada tikus malnutrisi [Effects of glutamine administration on sucrase, maltase, lactase and spectrin, clathrin expression in repairing ileal microvilli in malnutrition rats]. Jurnal Biosains Pascasarjana. 2012; 14: 48-60, article.

Huang ZX, Ye LY, Zheng ZY, Chen XM, Ren RN, Tong GY. Effect of glutamine on small intestinal repair in weanling rats after chronic diarrhea. Zhonghua Er Ke Za Zhi. 2005; 43: 368-72, PMID.

Kamuchaki J, Wobodeya E, Kiguli S, Bortolussi R. Efficacy of glutamine supplementation on the outcome of children admitted with persistent diarrhea in Uganda: A randomized controlled study. Paediatr. Child Health. 2013; 18(1): e1, CrossRef.

Federer WT. Experimental design, theory and application. New Delhi: Oxford and IBH Publ. Co; 1967.

Barthel M, Hapfelmeir S, Quintanilla LM, Kremer M, Rohde M, Hogardt M. Pretreatment of mice with streptomycin provides a Salmonella enterica serovar typhimurium colitis model that allows analysis of both pathogen and host. Infect Immun. 2003; 71: 2839-58, CrossRef.

Porsani MYH, Paludetti M, Orlando DR, Peconick AP, Costa RC, Oliveira LED, et al. Protective effect of β-glucan and glutamine on intestinal and immunological damage in mice induced by cytarabine (Ara-C). Pesq Vet Bras. 2017; 37: 977-83, CrossRef.

Zhou Q, Verne ML, Fields JZ, Lefante JJ, Basra S, Salameh H, Verne GN. Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome. BMJ. 2019; 68: 996-1002, CrossRef.

Chen K, Okuma T, Okamura K, Torigoe Y, Miyauchi Y. Glutamine-supplemented parenteral nutrition improves gut mucosa integrity and function in endotoxemic rats. J. Parenter Enteral Nutr. 1994; 18: 167-71, CrossRef.

Tannuri U, Carrazza F, Iriya K. The effects of glutamine-supplemented diet on the intestinal mucosa of the malnourished growing rat. Rev Hosp Clin. 2000; 55: 87-92, CrossRef.

Xu CL, Sun R, Qiao XJ, Xu CC, Shang XY, Niu WN. Protective effect of glutamine on intestinal injury andbacterial community in rats exposed to hypobaric hypoxiaenvironment. World J Gastroenterol. 2014; 20: 4662-74, CrossRef.

Zuhl MN, Lanphere KR, Kravitz L, Mermier CM, Schneider S, Dokladny K, et al. Effects of oral glutamine supplementation on exercise-induced gastrointestinal permeability and tight junction protein expression. J Appl Physiol. 2013; 116: 183-91, CrossRef.

Pithon-Curi TC, Schumacher RI, Freitas JJ, Lagranha C, Newsholme P, Palanch AC, et al. Glutamine delays spontaneous apoptosis in neutrophils. Am J Physiol Cell Physiol. 2003; 284: C1355-61, CrossRef.


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