Abstract
Background
Enterocolitis (EC) is the most common and serious postoperative complication of Hirschsprung’s disease (HD). Probiotics potentially play a protective role in maintaining intestinal mucosal integrity. Based on the beneficial effects of probiotics, we hypothesized that oral probiotics could decrease the incidence and severity of Hirschsprung’s disease-associated enterocolitis (HAEC).
Methods
We conducted a prospective, multicenter, randomized, and controlled trial to assess whether oral probiotics could decrease the incidence and severity of HAEC. HD patients were randomly assigned into the control group and probiotic-treated group. All children in probiotic-treated group were fed with probiotics per day for 4 weeks. In next 3 months, the incidence and severity of HAEC were analyzed. The peripheral blood T lymphocyte subsets and cytokines, including TNF-α, IFN-γ, IL-6, and IL-10, were analyzed by flow cytometry and enzyme immunoassay (EIA).
Results
Compared with the control group, the incidence of HAEC in the probiotic-treated group was significantly diminished. The severity of EC was also remarkably decreased. Furthermore, probiotics balanced T lymphocyte subsets. Moreover, pro-inflammatory cytokines TNF-α, IFN-γ, and IL-6 were significantly decreased and anti-inflammatory cytokine IL-10 was notably increased in probiotic-treated group.
Conclusions
Probiotics not only significantly diminished the incidence but also decreased the severity of HAEC. Moreover, our study revealed that probiotics decreased pro-inflammatory cytokine and increased anti-inflammatory cytokine and furthermore balanced T lymphocytes (registered with ClinicalTrials.gov, NCT number: NCT01934959).
Similar content being viewed by others
References
Lilly DM, Stillwell RH (1965) Probiotics: growth promoting factors by microorganisms. Sci 147:747–748
Fuller R (1989) Probiotics in man and animals. J Appl Bacteriol 66:365–378
Arnold C (2013) The pros and cons of probiotics. Lancet Infect Dis 13(7):571–572
Drouault-Holowacz S, Bieuvelet S, Burckel A, Cazaubiel M, Dray X, Marteau P (2008) A double blind randomized controlled trial of a probiotic combination in 100 patients with irritable bowel syndrome. Gastroenterol Clin Biol 32(2):147–152
Geier MS, Butler RN, Howarth GS (2007) Inflammatory bowel disease: current insights into pathogenesis and new therapeutic options; probiotics, prebiotics and synbiotics. Int J Food Microbiol 115(1):1–11
Imase K, Tanaka A, Tokunaga K, Sugano H, Ishida H, Takahashi S (2007) Lactobacillus reuteri tablets suppress Helicobacter pylori infection—a double-blind randomised placebo-controlled cross-over clinical study. Kansenshogaku Zasshi 81(4):387–393
Rafter J (2003) Probiotics and colon cancer. Best Pract Res Clin Gastroenterol 17(5):849–859
Barrons R, Tassone D (2008) Use of Lactobacillus probiotics for bacterial genitourinary infections in women: a review. Clin Ther 30(3):453–468
Schultz M, Timmer A, Herfarth HH, Sartor RB, Vanderhoof JA, Rath HC (2004) Lactobacillus GG in inducing and maintaining remission of Crohn’s disease. BMC Gastroenterol 4:5
Rosemary JY, Shari H (2003) Probiotic use in children. J Pediatr Health Care 17(6):277–283
Sari FN, Dizdar EA, Oguz S, Erdeve O, Uras N, Dilmen U (2011) Oral probiotics: Lactobacillus sporogenes for prevention of necrotizing enterocolitis in very low-birth weight infants: a randomized, controlled trial. Eur J Clin Nutr 65(4):434–439
Barclay AR, Stenson B, Simpson JH, Weaver LT, Wilson DC (2007) Probiotics for necrotizing enterocolitis: a systematic review. J Pediatr Gastroenterol Nutr 45(5):569–576
Kliegman RM (2005) Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants. J Pediatr 146(5):710
Lin HC, Su BH, Chen AC, Lin TW, Tsai CH, Yeh TF, Oh W (2005) Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants. Pediatr 115(1):1–4
Austin KM (2012) The pathogenesis of Hirschsprung’s disease-associated enterocolitis. Semin Pediatr Surg 21(4):319–327
Blanarova C, Galovicova A, Petrasova D (2009) Use of probiotics for prevention of radiation-induced diarrhea. Bratisl Lek Listy 110(2):98–104
Hackam DJ, Filler RM, Pearl RH (1998) Enterocolitis after the surgical treatment of Hirschsprung’s disease: risk factors and financial impact. J Pediatr Surg 33(6):830–833
Murphy F, Puri P (2005) New insights into the pathogenesis of Hirschsprung’s associated enterocolitis. Pediatr Surg Int 21(10):773–779
Elhalaby EA, Coran AG, Blane CE, Hirschl RB, Teitelbaum DH (1995) Enterocolitis associated with Hirschsprung’s disease: a clinical-radiological characterization based on 168 patients. J Pediatr Surg 30(1):76–83
Caneiro P, Brereton R, Drake D et al (1992) Enterocolitis in Hirschsprung’s disease. Pediatr Surg Int 7:356–360
Teitelbaum DH, Cilley RE, Sherman NJ, Bliss D, Uitvlugt ND, Renaud EJ, Kirstioglu I, Bengston T, Coran AG (2000) A decade of experience with the primary pull-through for Hirschsprung disease in the newborn period: a multicenter analysis of outcomes. Ann Surg 232(3):372–380
De Filippo C, Pini-Prato A, Mattioli G, Avanzini S, Rapuzzi G, Cavalieri D, Di Paola M, Stefanini I, Ceccherini I, Mavilio D, Lionetti P, Jasonni V (2010) Genomics approach to the analysis of bacterial communities dynamics in Hirschsprung’s disease-associated enterocolitis: a pilot study. Pediatr Surg Int 26:465–471
Wilson-Storey D, Scobie W (1989) Impaired gastrointestinal mucosal defense in Hirschsprung’s disease: a clue to the pathogenesis of enterocolitis? J Pediatr Surg 24:462–464
Caniano DA, Teitelbaum DH, Qualman SJ, Shannon BT (1989) The piebald–lethal murine strain: investigation of the cause of early death. J Pediatr Surg 24:906–910
Aslam A, Spicer RD, Corfield AP (1997) Children with Hirschsprung’s disease have an abnormal colonic mucus defensive barrier independent of the bowel innervation status. J Pediatr Surg 32:1206–1210
Reis EA, Hagan JE, Ribeiro GS, Teixeira-Carvalho A, Martins-Filho OA, Montgomery RR, Shaw AC, Ko AI, Reis MG (2013) Cytokine response signatures in disease progression and development of severe clinical outcomes for leptospirosis. PLoS Negl Trop Dis 7(9):e2457
Imamura A, Puri P, O’Briain DS, Reen DJ (1992) Mucosal immune defence mechanisms in enterocolitis complicating Hirschsprung’s disease. Gut 33(6):801–806
Frykman PK, Short SS (2012) Hirschsprung-associated enterocolitis: prevention and therapy. Semin Pediatr Surg 21(4):328–335
Acknowledgments
This study was funded by National Key Specialty ConstructionProgram (2013544) and National Natural Science Foundation of China (PI:Zhi Li;No:81400579).
Author contribution
Zhi Li and Xiaolin Wang wrote the manuscript. Jiexiong Feng designed the trial and revised the manuscript. Xiaolin Wang, Zhi Li, Zhilin Xu, Zhongrong Wang, and Jiexiong Feng coordinately conducted this trial.
Author information
Authors and Affiliations
Corresponding author
Additional information
Xiaolin Wang and Zhi Li had equal contribution to this manuscript.
Rights and permissions
About this article
Cite this article
Wang, X., Li, Z., Xu, Z. et al. Probiotics prevent Hirschsprung’s disease-associated enterocolitis: a prospective multicenter randomized controlled trial. Int J Colorectal Dis 30, 105–110 (2015). https://doi.org/10.1007/s00384-014-2054-0
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00384-014-2054-0