The Effect of Probiotic Supplementation on Serum Interleukin -23 Levels among Ulcerative Colitis Patients: a Pilot Study and Secondary Output
DOI:
https://doi.org/10.35516/jmj.v59i5.2429Keywords:
ulcerative colitis, probiotics, Interleukin-23Abstract
Background and aims: Interleukin (IL)-23 has gained particular attention as a proinflammatory cytokine playing key roles in the pathogenesis of ulcerative colitis. Recently, probiotics have been used more frequently in treating ulcerative colitis for induction and maintenance of remission. This study aimed to evaluate the effect of probiotic supplementation on IL-23 levels after remission induction in mild-to-moderately active ulcerative colitis patients in Jordan.
Methods: This is a pilot, multicenter, randomized, placebo-controlled, double-blind parallel-arms study. Twenty-four ulcerative colitis patients (11 men, 13 women) were randomly assigned to receive 3×1010 probiotic 10 billion active cells or three capsules of placebo daily for six weeks. Partial mayo score and serum level of IL-23 were measured at baseline and after six weeks.
Results: There was a significant difference in the mean Partial Mayo score between the probiotic group and the placebo group at the end of the study (1.33 ± 0.49 vs 3.42 ± 1.78) (p<0.001). The probiotics' IL-23 level was insignificantly reduced compared to the placebo group (p>0.05). Similarly, there were no significant differences in the mean or percentage change in the IL-23 level between the two groups (p>0.05).
Conclusions: Probiotic supplementation had an insignificant suppressive effect on IL-23 levels. However, it still offered a beneficial therapeutic effect for patients with ulcerative colitis, as evidenced by an improvement in the Partial Mayo score.
References
Cosnes J, Gower-Rousseau C, Seksik P, Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology 2011; 140(6): 1785-94.
Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology 2004; 126(6): 1504-17.
Baumgart DC, Carding SR. Inflammatory bowel disease: Cause and immunobiology. Lancet 2007; 369(9573): 1627-40.
Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 2006; 12(Suppl. 1): S3-9.
Danese S. Immune and nonimmune components orchestrate the pathogenesis of inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 2011; 300(5): G716-22.
Montalban-Arques A, Chaparro M, Gisbert JP, Bernardo D. The innate immune system in the gastrointestinal tract: Role of intraepithelial lymphocytes and lamina propria innate lymphoid cells in intestinal inflammation. Inflamm Bowel Dis 2018; 24(8): 1649-59.
Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature 2011; 474(7351): 307-17.
Troncone E, Marafini I, Pallone F, Monteleone G. Th17 cytokines in inflammatory bowel diseases: discerning the good from the bad. Int rev immunol. 2013 Oct 1;32(5-6):526-33.
Rossi M, Bot A. The Th17 cell population and the immune homeostasis of the gastrointestinal tract. Int rev immunol. 2013 Oct 1;32(5-6):471-4.
Lubberts E. The IL-23-IL-17 axis in inflammatory arthritis. Nat Rev Rheumatol 2015; 11(7): 415-29.
Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, Ouyang W. Interleukin-22, a T (H) 17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 2007;445:648e51.
Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annu Rev Immunol 2009;27:485e517.
Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ, McKenzie BS, Powrie F, Maloy KJ. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J Exp Med 2006;203: 2473e83.
Brennan FM, McInnes IB. Evidence that cytokines play a role in rheumatoid arthritis. J Clin Invest 2008;118:3537e41.
El-Bassat H, AboAli L, El Yamany S, Al Shenawy H, Al-Din RA, Taha A. Interleukin-23p19 expression in patients with ulcerative colitis and its relation to disease severity. Adv Dig Med. 2016 Sep 1;3(3):88-94.
Guandalini S, Sansotta N. Probiotics in the Treatment of Inflammatory Bowel Disease. Adv Exp Med Biol. 2019;1125:101-107.
Dupaul-Chicoine J, Dagenais M, Saleh M. Crosstalk between the intestinal microbiota and the innate immune system in intestinal homeostasis and inflammatory bowel disease. Inflamm bowel dis. 2013 Sep 1;19(10):2227-37.
Chen L, Zou Y, Peng J, Lu F, Yin Y, Li F, Yang J. Lactobacillus acidophilus suppresses colitis-associated activation of the IL-23/Th17 axis. J Immunol Res. 2015;2015.
Ghadimi D, Helwig U, Schrezenmeir J, Heller KJ, de Vrese M. Epigenetic imprinting by commensal probiotics inhibits the IL‐23/IL‐17 axis in an in vitro model of the intestinal mucosal immune system. J leukoc biol. 2012;92(4):895-911.
Bibiloni R, Fedorak RN, Tannock GW, et al. VSL# 3 probiotic-mixture induces remission in patients with active ulcerative colitis. Am J Gastroenterol 2005;100(7):1539-46.
Sood A, Midha V, Makharia GK, et al. The probiotic preparation, VSL# 3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clin Gastroenterol Hepatol 2009;7(11):1202-1209.
Tursi A, Brandimarte G, Papa A, et al. Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL# 3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebo-controlled study. Am J Gastroenterol 2010;105(10):2218.
Agraib LM, Yamani MI, Tayyem R, Abu-Sneineh AT, Rayyan YM. Probiotic supplementation induces remission and changes in the immunoglobulins and inflammatory response in active ulcerative colitis patients: A pilot, randomized, double-blind, placebo-controlled study. Clinical Nutrition ESPEN. 2022;51:83-91.
Elson CO, Cong Y. Host-microbiota interactions in inflammatory bowel disease. Gut microbes. 2012 Jul 14;3(4):332-44.
Ueno A, Jijon H, Chan R, Ford K, Hirota C, Kaplan GG, Beck PL, Iacucci M, Fort Gasia M, Barkema HW, Panaccione R. Increased prevalence of circulating novel IL-17 secreting Foxp3 expressing CD4+ T cells and defective suppressive function of circulating Foxp3+ regulatory cells support plasticity between Th17 and regulatory T cells in inflammatory bowel disease patients. Inflamm bowel dis. 2013 Nov 1;19(12):2522-34.
Hölttä V, Klemetti P, Salo HM, Koivusalo A, Pakarinen M, Westerholm-Ormio M, Kolho KL, Vaarala O. Interleukin-17 immunity in pediatric Crohn disease and ulcerative colitis. J Pediatr Gastroenterol Nutr. 2013 Sep 1;57(3):287-92.
Bamola VD, Dubey D, Samanta P, Kedia S, Ahuja V, Madempudi RS, Neelamraju J, Chaudhry R. Role of a probiotic strain in the modulation of gut microbiota and cytokines in inflammatory bowel disease. Anaerobe. 2022 Oct 2;78:102652. doi: 10.1016/j.anaerobe.2022.102652. Epub ahead of print.
Zhang Z, Andoh A, Yasui H, Inatomi O, Hata K, Tsujikawa T, Kitoh K, Takayanagi A, Shimizu N, Fujiyama Y. Interleukin-1β and tumor necrosis factor-α upregulate interleukin-23 subunit p19 gene expression in human colonic subepithelial myofibroblasts. Int J Mol Med. 2005 Jan 1;15(1):79-83.
Leccese G, Bibi A, Mazza S, Facciotti F, Caprioli F, Landini P, Paroni M. Probiotic Lactobacillus and Bifidobacterium strains counteract adherent-invasive Escherichia coli (AIEC) virulence and hamper IL-23/Th17 axis in ulcerative colitis, but not in Crohn's disease. Cells. 2020 Aug 1;9(8):1824.
Caprioli F, Pallone F, Monteleone G. Th17 immune response in IBD: A new pathogenic mechanism. J Crohn's Colitis. 2008 Dec 1;2(4):291-5.
Bsat M, Chapuy L, Rubio M, Wassef R, Richard C, Schwenter F, Loungnarath R, Soucy G, Mehta H, Sarfati M. Differential pathogenic Th17 profile in mesenteric lymph nodes of Crohn's disease and ulcerative colitis patients. Front Immunol. 2019 May 28;10:1177.
Isidro RA, Bonilla FJ, Pagan H, Cruz ML, Lopez P, Godoy L, Hernandez S, Loucil-Alicea RY, Rivera-Amill V, Yamamura Y, Isidro AA, Appleyard CB. The Probiotic Mixture VSL#3 Alters the Morphology and Secretion Profile of Both Polarized and Unpolarized Human Macrophages in a Polarization-Dependent Manner. J Clin Cell Immunol. 2014 Jun 20;5(3):1000227. doi: 10.4172/2155-9899.1000227. PMID: 25177525; PMCID: PMC4145411.
Turroni F, Duranti S, Milani C, Lugli GA, van Sinderen D, Ventura M. Bifidobacterium bifidum: a key member of the early human gut microbiota. Microorganisms. 2019;7:544.
