ROLE OF PROKINETIC AGENTS IN PREVENTING SMALL INTESTINAL BACTERIAL OVERGROWTH (SIBO) RECURRENCE: A NARRATIVE REVIEW

Authors

DOI:

https://doi.org/10.31435/ijitss.3(51).2026.5819

Keywords:

Small Intestinal Bacterial Overgrowth; SIBO; Prokinetic Agents; Migrating Motor Complex; MMC; Gastrointestinal Motility

Abstract

Background: Small intestinal bacterial overgrowth (SIBO) involves the pathological proliferation of bacteria in the small bowel, causing symptoms like bloating and abdominal pain. Although rifaximin is effective for initial eradication, the condition frequently relapses. This recurrence is primarily driven by the failure of the migrating motor complex (MMC), specifically its phase III "housekeeping" function.

Aim: This review evaluates the clinical utility of prokinetic agents in maintaining SIBO remission and examines whether their administration extends the symptom-free interval in high-risk populations.

Material and methods: A systematic search of PubMed and Scopus was conducted to synthesize evidence on MMC dysfunction and the efficacy of various prokinetic agents in preventing bacterial regrowth.

Results: Research indicates that SIBO patients experience a 60% reduction in MMC-related clearance compared to healthy controls. The synergistic integration of prokinetic therapy into the antibiotic eradication phase has been shown to significantly enhance bacterial clearance rates. Among these agents, prucalopride demonstrates high efficacy in delaying relapses and extending the duration of remission. Clinical success depends heavily on nocturnal dosing during the interdigestive state to maximize mechanical cleansing.

Conclusions: Prokinetic pharmacotherapy is an essential component of maintaining remission in SIBO by directly addressing MMC dysfunction - the primary pathophysiological cause of relapse. The selection of a therapeutic agent should be tailored to the patient’s clinical phenotype, considering metabolic safety and the symptom profile. Despite promising data, this review underscores the need for large-scale randomized controlled trials to establish standardized diagnostic and therapeutic guidelines.

References

Allescher, H.-D., Burgell, R., Malfertheiner, P., & Mearin, F. (2020). Multi-target treatment for irritable bowel syndrome with STW 5: Pharmacological modes of action. Journal of Gastrointestinal and Liver Diseases, 29(2), 227–233. https://doi.org/10.15403/jgld-814

von Arnim, U., Peitz, U., Vinson, B., Gundermann, K.-J., & Malfertheiner, P. (2007). STW 5, a phytopharmacon for patients with functional dyspepsia: Results of a multicenter, placebo-controlled double-blind study. The American Journal of Gastroenterology, 102(6), 1268–1275. https://doi.org/10.1111/j.1572-0241.2006.01183.x

Bianco, F., Bonora, E., Natarajan, D., et al. (2016). Prucalopride exerts neuroprotection in human enteric neurons. American Journal of Physiology-Gastrointestinal and Liver Physiology, 310(10), G768–G775. https://doi.org/10.1152/ajpgi.00036.2016

Broeders, B., Tack, J., & Talley, N. J. (2025). Itopride in functional dyspepsia: Open-label, 1-year treatment follow-up of two multicenter, randomized, double-blind, placebo-controlled trials. Therapeutic Advances in Gastroenterology, 18, 17562848251321123. https://doi.org/10.1177/17562848251321123

Bures, J., Cyrany, J., Kohoutova, D., et al. (2010). Small intestinal bacterial overgrowth syndrome. World Journal of Gastroenterology, 16(24), 2978–2990. https://doi.org/10.3748/wjg.v16.i24.2978

Bushyhead, D., & Quigley, E. M. M. (2022). Small intestinal bacterial overgrowth—Pathophysiology and its implications for definition and management. Gastroenterology, 163(3), 593–607. https://doi.org/10.1053/j.gastro.2022.04.002

Camilleri, M., Piessevaux, H., Yiannakou, Y., et al. (2016). Efficacy and safety of prucalopride in chronic constipation: An integrated analysis of six randomized, controlled clinical trials. Digestive Diseases and Sciences, 61, 2357–2372. https://doi.org/10.1007/s10620-016-4147-9

Carbone, F., Van den Houte, K., Clevers, E., et al. (2019). Prucalopride in gastroparesis: A randomized placebo-controlled crossover study. The American Journal of Gastroenterology, 114(8), 1265. https://doi.org/10.14309/ajg.0000000000000304

Chaussade, S., Grandjouan, S., Couturier, D., Thierman-Duffaud, D., & Henry, J. F. (1987). Induction of phase 3 of the migrating motor complex in human small intestine by trimebutine. European Journal of Clinical Pharmacology, 32(6), 615–618. https://doi.org/10.1007/BF02455998

Chedid, V., Dhalla, S., Clarke, J. O., et al. (2014). Herbal therapy is equivalent to rifaximin for the treatment of small intestinal bacterial overgrowth. Global Advances in Health and Medicine, 3(3), 16–24. https://doi.org/10.7453/gahmj.2014.019

Deeraksa, C. (2024). Erythromycin drug interactions: A comprehensive review. Journal of Pharmacovigilance. https://www.hilarispublisher.com/open-access/erythromycin-drug-interactions-a-comprehensive-review-108626.html

Deloose, E., Janssen, P., Depoortere, I., & Tack, J. (2012). The migrating motor complex: Control mechanisms and its role in health and disease. Nature Reviews Gastroenterology & Hepatology, 9(5), 271–285. https://doi.org/10.1038/nrgastro.2012.57

Deloose, E., & Tack, J. (2016). Redefining the functional roles of the gastrointestinal migrating motor complex and motilin in small bacterial overgrowth and hunger signaling. American Journal of Physiology-Gastrointestinal and Liver Physiology, 310(4), G228–G233. https://doi.org/10.1152/ajpgi.00212.2015

Dite, P., Rydlo, M., Dockal, M., & Martinek, A. (2014). A prokinetic agent with a dual effect—Itopride—in the treatment of dysmotility. EMJ Gastroenterology, 42–47. https://doi.org/10.33590/emjgastroenterol/10314653

Foxx-Orenstein, A. E., Camilleri, M., Szarka, L. A., et al. (2007). Does co-administration of a non-selective opiate antagonist enhance acceleration of transit by a 5-HT4 agonist in constipation-predominant irritable bowel syndrome? A randomized controlled trial. Neurogastroenterology & Motility, 19(10), 821–830. https://doi.org/10.1111/j.1365-2982.2007.00944.x

Gatta, L., Scarpignato, C., McCallum, R. W., et al. (2017). Systematic review with meta-analysis: Rifaximin is effective and safe for the treatment of small intestine bacterial overgrowth. Alimentary Pharmacology & Therapeutics, 45(5), 604–616. https://doi.org/10.1111/apt.13928

Giacosa, A., Guido, D., Grassi, M., et al. (2015). The effect of ginger (Zingiber officinalis) and artichoke (Cynara cardunculus) extract supplementation on functional dyspepsia: A randomised, double-blind, and placebo-controlled clinical trial. Evidence-Based Complementary and Alternative Medicine, 2015, 915087. https://doi.org/10.1155/2015/915087

Hawkyard, C. V., & Koerner, R. J. (2007). The use of erythromycin as a gastrointestinal prokinetic agent in adult critical care: Benefits versus risks. Journal of Antimicrobial Chemotherapy, 59(3), 347–358. https://doi.org/10.1093/jac/dkl537

Hu, M.-L., Rayner, C. K., Wu, K.-L., et al. (2011). Effect of ginger on gastric motility and symptoms of functional dyspepsia. World Journal of Gastroenterology, 17(1), 105–110. https://doi.org/10.3748/wjg.v17.i1.105

Huang, X., Lv, B., Zhang, S., Fan, Y.-H., & Meng, L.-N. (2012). Itopride therapy for functional dyspepsia: A meta-analysis. World Journal of Gastroenterology, 18(48), 7371–7377. https://doi.org/10.3748/wjg.v18.i48.7371

Jo, I. H., Paik, C.-N., Lee, J. M., Song, D. S., & Kim, Y.-J. (2024). Effect of trimebutine and rifaximin on breath hydrogen and methane by glucose breath test in patients with functional bloating: A randomized double-blind clinical trial. Journal of Neurogastroenterology and Motility, 30(2), 220–228. https://doi.org/10.5056/jnm23029

Kariv, R., Tiomny, E., Grenshpon, R., et al. (2006). Low-dose naltreoxone for the treatment of irritable bowel syndrome: A pilot study. Digestive Diseases and Sciences, 51(12), 2128–2133. https://doi.org/10.1007/s10620-006-9289-8

Kessing, B. F., Smout, A. J. P. M., Bennink, R. J., Kraaijpoel, N., Oors, J. M., & Bredenoord, A. J. (2014). Prucalopride decreases esophageal acid exposure and accelerates gastric emptying in healthy subjects. Neurogastroenterology & Motility, 26(8), 1079–1086. https://doi.org/10.1111/nmo.12359

Konen, J. R., Haag, M. M., Guseva, D., et al. (2021). Pro-kinetic actions of luminally-acting 5-HT4 receptor agonists. Neurogastroenterology & Motility, 33(4), e14026. https://doi.org/10.1111/nmo.14026

Larson, J. M., Tavakkoli, A., Drane, W. E., Toskes, P. P., & Moshiree, B. (2010). Advantages of azithromycin over erythromycin in improving the gastric emptying half-time in adult patients with gastroparesis. Journal of Neurogastroenterology and Motility, 16(4), 407–413. https://doi.org/10.5056/jnm.2010.16.4.407

Lauritano, E. C., Gabrielli, M., Scarpellini, E., Lupascu, A., et al. (2008). Small intestinal bacterial overgrowth recurrence after antibiotic therapy. The American Journal of Gastroenterology. Advance online publication. https://doi.org/10.1111/j.1572-0241.2008.02030.x

Liu, M.-T., Kuan, Y.-H., Wang, J., Hen, R., & Gershon, M. D. (2009). 5-HT4 receptor-mediated neuroprotection and neurogenesis in the enteric nervous system of adult mice. The Journal of Neuroscience, 29(31), 9683–9699. https://doi.org/10.1523/JNEUROSCI.1145-09.2009

Lo, W.-K., & Chan, W. W. (2013). Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: A meta-analysis. Clinical Gastroenterology and Hepatology, 11(5), 483–490. https://doi.org/10.1016/j.cgh.2012.12.011

Madisch, A., Holtmann, G., Plein, K., & Hotz, J. (2004). Treatment of irritable bowel syndrome with herbal preparations: Results of a double-blind, randomized, placebo-controlled, multi-centre trial. Alimentary Pharmacology & Therapeutics, 19(3), 271–279. https://doi.org/10.1111/j.1365-2036.2004.01859.x

Mendzelevski, B., Ausma, J., Chanter, D. O., et al. (2012). Assessment of the cardiac safety of prucalopride in healthy volunteers: A randomized, double-blind, placebo- and positive-controlled thorough QT study. British Journal of Clinical Pharmacology, 73(2), 203–209. https://doi.org/10.1111/j.1365-2125.2011.04088.x

von Muhlenbrock, C., Landskron, G., & Madrid, A. M. (2025). Treatment of small intestinal bacterial overgrowth in Chilean patients with irritable bowel syndrome: A prospective and comparative study. Revista de Gastroenterología de México (English Edition), 90(1), 54–62. https://doi.org/10.1016/j.rgmxen.2024.08.003

Mulak, A. (2014). Leki prokinetyczne w Polsce—Kiedy i jak stosować? Gastroenterologia Kliniczna. Postępy i Standardy, 6(4), 134–142. https://journals.viamedica.pl/gastroenterologia_kliniczna/article/view/40607/28186

Nasr, I., Rao, S. S. C., Attaluri, A., Hashmi, S. M. A., & Summers, R. (2009). Effects of tegaserod and erythromycin in upper gut dysmotility: A comparative study. Indian Journal of Gastroenterology, 28(4), 136–142. https://doi.org/10.1007/s12664-009-0048-6

Nikkhah Bodagh, M., Maleki, I., & Hekmatdoost, A. (2019). Ginger in gastrointestinal disorders: A systematic review of clinical trials. Food Science & Nutrition, 7(1), 96–108. https://doi.org/10.1002/fsn3.807

Ottillinger, B., Storr, M., Malfertheiner, P., & Allescher, H.-D. (2013). STW 5 (Iberogast®)—A safe and effective standard in the treatment of functional gastrointestinal disorders. Wiener Medizinische Wochenschrift, 163(3–4), 65–72. https://doi.org/10.1007/s10354-012-0169-x

Pimentel, M., Lin, H. C., Enayati, P., et al. (2006). Methane, a gas produced by enteric bacteria, slows intestinal transit and augments small intestinal contractile activity. American Journal of Physiology-Gastrointestinal and Liver Physiology, 290(6), G1089–G1095. https://doi.org/10.1152/ajpgi.00574.2004

Pimentel, M., Morales, W., Lezcano, S., Sun-Chuan, D., Low, K., & Yang, J. (2009). Low-dose nocturnal tegaserod or erythromycin delays symptom recurrence after treatment of irritable bowel syndrome based on presumed bacterial overgrowth. Gastroenterology & Hepatology, 5(6), 435–442. https://pmc.ncbi.nlm.nih.gov/articles/PMC2886395/

Pimentel, M., Morales, W., Rezaie, A., et al. (2015). Development and validation of a biomarker for diarrhea-predominant irritable bowel syndrome in human subjects. PLOS ONE, 10(5), e0126438. https://doi.org/10.1371/journal.pone.0126438

Pimentel, M., Saad, R. J., Long, M. D., & Rao, S. S. C. (2020). ACG clinical guideline: Small intestinal bacterial overgrowth. The American Journal of Gastroenterology, 115(2), 165–178. https://doi.org/10.14309/ajg.0000000000000501

Pimentel, M., Soffer, E. E., Chow, E. J., Kong, Y., & Lin, H. C. (2002). Lower frequency of MMC is found in IBS subjects with abnormal lactulose breath test, suggesting bacterial overgrowth. Digestive Diseases and Sciences, 47(12), 2639–2643. https://doi.org/10.1023/A:1021039032413

Ploesser, J., Weinstock, L. B., & Thomas, E. (2010). Low dose naltrexone: Side effects and efficacy in gastrointestinal disorders. International Journal of Pharmaceutical Compounding, 14(2), 171–173. https://pubmed.ncbi.nlm.nih.gov/23965429/

Poynard, T., Regimbeau, C., & Benhamou, Y. (2001). Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome. Alimentary Pharmacology & Therapeutics, 15(3), 355–361. https://doi.org/10.1046/j.1365-2036.2001.00937.x

Quigley, E. M. M. (2017). Prokinetics in the management of functional gastrointestinal disorders. Current Gastroenterology Reports, 19(10), 53. https://doi.org/10.1007/s11894-017-0593-6

Raedsch, R., Hanisch, J., Bock, P., Sibaev, A., Vinson, B., & Gundermann, K. J. (2007). Wirksamkeit und Unbedenklichkeit des Phytopharmakons STW 5 versus Metoclopramid bei funktioneller Dyspepsie unter Praxisbedingungen—Eine retrolektive Kohortenstudie. Zeitschrift für Gastroenterologie, 45(10), 1041–1048. https://doi.org/10.1055/s-2007-963357

Rao, S. S. C., Rehman, A., Yu, S., & Martinez de Andino, N. (2018). Brain fogginess, gas and bloating: A link between SIBO, probiotics and metabolic acidosis. Clinical and Translational Gastroenterology, 9(6), 162. https://doi.org/10.1038/s41424-018-0030-7

Rezaie, A., Pimentel, M., & Rao, S. S. (2016). How to test and treat small intestinal bacterial overgrowth: An evidence-based approach. Current Gastroenterology Reports, 18(2), 8. https://doi.org/10.1007/s11894-015-0482-9

Rösch, W., Vinson, B., & Sassin, I. (2002). A randomised clinical trial comparing the efficacy of a herbal preparation STW 5 with the prokinetic drug cisapride in patients with dysmotility type of functional dyspepsia. Zeitschrift für Gastroenterologie, 40(6), 401–408. https://doi.org/10.1055/s-2002-32130

Schemann, M., Michel, K., Zeller, F., Hohenester, B., & Rühl, A. (2006). Region-specific effects of STW 5 (Iberogast®) and its components in gastric fundus, corpus and antrum. Phytomedicine, 13, 90–99. https://doi.org/10.1016/j.phymed.2006.03.020

Silva, B. C. da, Ramos, G. P., Barros, L. L., et al. (2025). Diagnosis and treatment of small intestinal bacterial overgrowth: An official position paper from the Brazilian Federation of Gastroenterology. Arquivos de Gastroenterologia, 62, e24107. https://doi.org/10.1590/S0004-2803.24612024-107

Smith, J. P., Stock, H., Bingaman, S., Mauger, D., Rogosnitzky, M., & Zagon, I. S. (2007). Low-dose naltrexone therapy improves active Crohn’s disease. The American Journal of Gastroenterology, 102(4), 820–828. https://journals.lww.com/ajg/abstract/2007/04000/low_dose_naltrexone_therapy_improves_active.19.aspx

Staudacher, H. M., & Whelan, K. (2017). The low FODMAP diet: Recent advances in understanding its mechanisms and efficacy in IBS. Gut, 66(8), 1517–1527. https://doi.org/10.1136/gutjnl-2017-313750

Tack, J., Camilleri, M., Chang, L., et al. (2012). Systematic review: Cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders. Alimentary Pharmacology & Therapeutics, 35(7), 745–767. https://doi.org/10.1111/j.1365-2036.2012.05011.x

Takakura, W., & Pimentel, M. (2020). Small intestinal bacterial overgrowth and irritable bowel syndrome—An update. Frontiers in Psychiatry, 11, 664. https://doi.org/10.3389/fpsyt.2020.00664

Takakura, W., Rezaie, A., Chey, W. D., Wang, J., & Pimentel, M. (2024). Symptomatic response to antibiotics in patients with small intestinal bacterial overgrowth: A systematic review and meta-analysis. Journal of Neurogastroenterology and Motility, 30(1), 7–16. https://doi.org/10.5056/jnm22187

Tonini, M., Cipollina, L., Poluzzi, E., Crema, F., Corazza, G. R., & De Ponti, F. (2004). Review article: Clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics. Alimentary Pharmacology & Therapeutics, 19(4), 379–390. https://doi.org/10.1111/j.1365-2036.2004.01867.x

Tsubouchi, T., Saito, T., Mizutani, F., Yamauchi, T., & Iwanaga, Y. (2003). Stimulatory action of itopride hydrochloride on colonic motor activity in vitro and in vivo. The Journal of Pharmacology and Experimental Therapeutics, 306(2), 787–793. https://doi.org/10.1124/jpet.102.048603

Usai-Satta, P., Lai, M., Oppia, F., & Cabras, F. (2022). Effects of prokinetics on the digestive tract. Current Reviews in Clinical and Experimental Pharmacology, 17(3), 161–165. https://doi.org/10.2174/2772432816666210805125813

Weinstock, L. B., Myers, T. L., Walters, A. S., et al. (2016). Identification and treatment of new inflammatory triggers for complex regional pain syndrome: Small intestinal bacterial overgrowth and obstructive sleep apnea. A&A Practice, 6(9), 272–276. https://doi.org/10.1213/XAA.0000000000000292

Wong, B. S., Manabe, N., & Camilleri, M. (2010). Role of prucalopride, a serotonin (5-HT4) receptor agonist, for the treatment of chronic constipation. Clinical and Experimental Gastroenterology, 3, 49–56. https://doi.org/10.2147/CEG.S8091

Yang, T., Wang, K., Cao, Y., et al. (2021). Different doses of prucalopride in treating chronic idiopathic constipation: A meta-analysis and Bayesian analysis. BMJ Open, 11(2), e039461. https://doi.org/10.1136/bmjopen-2020-039461

Yang, Y. J., Bang, C. S., Baik, G. H., et al. (2017). Prokinetics for the treatment of functional dyspepsia: Bayesian network meta-analysis. BMC Gastroenterology, 17, 83. https://doi.org/10.1186/s12876-017-0639-0

Younger, J., Parkitny, L., & McLain, D. (2014). The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clinical Rheumatology, 33(4), 451–459. https://doi.org/10.1007/s10067-014-2517-2

Zhang, Q., Li, H., Chen, C., et al. (2025). Comparative efficacy of diverse therapeutic regimens for small intestinal bacterial overgrowth: A systematic network meta-analysis. Therapeutic Advances in Gastroenterology, 18, 17562848251399033. https://doi.org/10.1177/17562848251399033

Downloads

Published

2026-08-24

How to Cite

Kasperska, A., Kłuś, A., Zhaharina, I., Manila, Y., Dubova, Y., Markowska, H., Sienicka, M., Kobiałkowski, Łukasz, & Doroshkov, V. (2026). ROLE OF PROKINETIC AGENTS IN PREVENTING SMALL INTESTINAL BACTERIAL OVERGROWTH (SIBO) RECURRENCE: A NARRATIVE REVIEW. International Journal of Innovative Technologies in Social Science, 2(3(51). https://doi.org/10.31435/ijitss.3(51).2026.5819

Most read articles by the same author(s)

<< < 1 2