Probiotics in pediatric cardiac surgery: biological effects and clinical outcomes – a systematic review of randomized evidence

Authors

  • Muhammad Shahzad Department of Pediatric Cardiac Surgical ICU, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  • Mohammed S. Aldughaythir Department of Pediatric Cardiac Surgical ICU, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  • Fai Alanazi Department of Pediatric Cardiac Surgical ICU, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  • Abdulaziz Alanazi Department of Pediatric Cardiac Surgical ICU, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  • Mashail Alghamdi Department of Pediatric Cardiac Surgical ICU, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  • Hend Alharbi Department of Pediatric Cardiac Surgical ICU, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  • Sarah Alsubaie Department of Critical Care Nursing, Pediatric Cardiac Surgical ICU, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  • Lina Alshabanah College of Medicine, Alfaisal University, Saudi Arabia
  • Joud Almohrij College of Medicine, Alfaisal University, Saudi Arabia

DOI:

https://doi.org/10.18203/2349-3291.ijcp20263822

Keywords:

Probiotics, Cardiac surgery, Cardiopulmonary bypass, Randomized controlled trials, Pilot study, Outcome

Abstract

Children undergoing cardiac surgery with cardiopulmonary bypass (CPB) are vulnerable to intestinal barrier dysfunction, systemic inflammation, and postoperative infection. Probiotics may restore gut microbiota balance and modulate inflammation, but evidence in pediatric cardiac populations is limited. The objective is to systematically analyze the effects of perioperative probiotic supplementation in pediatric cardiac surgery, and incorporating indirect evidence from adult CPB trials. Following PRISMA 2020 guidelines, major databases (PubMed, Embase, Scopus, CENTRAL, and ClinicalTrials.gov) were searched through March 2025. Eligible studies were randomized controlled trial (RCTs) and pilot studies that evaluated the probiotics in pediatric or adult cardiac-surgery patients. Data extraction and risk-of-bias assessment (RoB2) were performed independently by three reviewers. Owing to clinical heterogeneity and sparse events, findings were narratively synthesized, with quantitative pooling limited to comparable continuous outcomes. Five RCTs (three pediatric, two adult) met the inclusion criteria. Pediatric trials using Bifidobacterium breve or Bifidobacterium longum demonstrated improved intestinal microbiota and trends toward reduced endotoxin and I-FABP levels, but no significant differences in infection or ICU length of stay. Adult CPB trials showed reduced acute gastrointestinal injury and nosocomial infections. No adverse events or probiotic-associated sepsis were reported. Overall certainty of evidence ranged from low to moderate, limited by sample size and outcome heterogeneity. Perioperative probiotic supplementation in pediatric cardiac surgery appears safe and biologically active but lacks conclusive evidence for clinical benefit. Larger, standardized multicenter RCTs are warranted to determine efficacy and optimize strain selection, dosing, and timing.

References

Martins C, Gama BMN. Risk Factors for Mortality in Pediatric Cardiac Intensive Care Unit. Int J Cardiovasc Sci. 2020;33:337-9.

Shahzad M, Alheraish YA, Beheri RM, Alarwan K. Integrated care in cardiac intensive care unit for noncardiovascular complications in children after open-heart surgery: A comprehensive review. J Pediatr Crit Care. 2023;10(5):220-7.

Zhang Y, Luo W, Zhao M, Li Y, Wu X. Advances in understanding the effects of cardiopulmonary bypass on gut microbiota during cardiac surgery. Int J Artif Organs. 2025;48(2):51-63.

Salomon J, Ericsson A, Price A, Manithody C, Murry DJ, Chhonker YS, et al. Dysbiosis and Intestinal Barrier Dysfunction in Pediatric Congenital Heart Disease Is Exacerbated Following Cardiopulmonary Bypass. JACC Basic Transl Sci. 2021;6(4):311-27.

Yang X, Liu R, An Z, Li B, Lin Y, Li Y, et al. Probiotic mitigates gut hypoperfusion-associated acute gastrointestinal injury in patients undergoing cardiopulmonary bypass: a randomized controlled trial. BMC Med. 2025;23(1):238.

Sharif S, Meader N, Oddie SJ, Rojas-Reyes MX, McGuire W. Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. Cochrane Database Syst Rev. 2023;7(7):CD005496.

Lou J, Cui S, Huang N, Jin G, Chen C, Fan Y, et al. Efficacy of probiotics or synbiotics in critically ill patients: A systematic review and meta-analysis. Clin Nutr ESPEN. 2024;59:48-62.

Haddaway NR, Page MJ, Pritchard CC, McGuinness LA. PRISMA 2020: An R package and Shiny app for producing PRISMA 2020-compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis. Campbell Syst Rev. 2022;18(2):e1230.

Cochrane. Cochrane Handbook for Systematic Reviews of Interventions. Available at: https://www.cochrane.org/authors/handbooks-and-manuals/handbook#how-to-cite. Accessed on 13 November 2025.

Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 8. Rating the quality of evidence--indirectness. J Clin Epidemiol. 2011;64(12):1303-10.

Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135.

Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.

Rodgers M, Sowden A, Petticrew M, Arai L, Roberts H, Britten N, et al. Testing Methodological Guidance on the Conduct of Narrative Synthesis in Systematic Reviews: Effectiveness of Interventions to Promote Smoke Alarm Ownership and Function. Evaluation. 2009;15(1):49-73.

DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177-88.

Friedrich JO, Adhikari NKJ, Beyene J. Inclusion of zero total event trials in meta-analyses maintains analytic consistency and incorporates all available data. BMC Med Res Methodol. 2007;7:5.

Ellis CL, Bokulich NA, Kalanetra KM, Mirmiran M, Elumalai J, Haapanen L, et al. Probiotic administration in congenital heart disease: a pilot study. J Perinatol. 2013;33(9):691-7.

Umenai T, Shime N, Asahara T, Nomoto K, Itoi T. A pilot study of Bifidobacterium breve in neonates undergoing surgery for congenital heart disease. J Intensive Care. 2014;2:36.

Toritsuka D, Aoki M, Higashida A, Fukahara K, Nishida N, Hirono K, et al. Probiotics may alleviate intestinal damage induced by cardiopulmonary bypass in children. Eur J Cardiothorac Surg. 2024;65(4):ezae152.

Liu WC, Zhan YP, Wang XH, Hou BC, Huang J, Chen SB. Comprehensive preoperative regime of selective gut decontamination in combination with probiotics, and smectite for reducing endotoxemia and cytokine activation during cardiopulmonary bypass: A pilot randomized, controlled trial. Medicine (Baltimore). 2018;97(46):e12685.

Magner C, Jenkins D, Koc F, Tan MH, O'Toole M, Boyle J, et al. Protocol for a prospective cohort study exploring the gut microbiota of infants with congenital heart disease undergoing cardiopulmonary bypass (the GuMiBear study). BMJ Open. 2023;13(3):e067016.

Koc F, Magner C, Murphy K, Kelleher ST, Tan MH, O'Toole M, et al. Gut Microbiome in Children with Congenital Heart Disease After Cardiopulmonary Bypass Surgery (GuMiBear Study). Pediatr Cardiol. 2025;46(7):1868-78.

Chen Y, Qi A, Teng D, Li S, Yan Y, Hu S, et al. Probiotics and synbiotics for preventing postoperative infectious complications in colorectal cancer patients: a systematic review and meta-analysis. Tech Coloproctol. 2022;26(6):425-36.

Suez J, Zmora N, Zilberman-Schapira G, Mor U, Dori-Bachash M, Bashiardes S, et al. Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT. Cell. 2018;174(6):1406-23.

Shahzad M, Alheraish YA, Algethami B, Algheryafi LA, Kamel S, Ghunaim R, et al. Original Article--Risk Factors for Neurological Complications and Short-term Outcomes After Pediatric Heart Surgery: A Retrospective Analysis. J Saudi Heart Assoc. 2024;36(1):8-13.

Angurana SK. Probiotics in the Pediatric ICU: Beyond Blurred Lines. Chest. 2017;152:685-6.

Plaza-Díaz J, Ruiz-Ojeda FJ, Vilchez-Padial LM, Gil A. Evidence of the Anti-Inflammatory Effects of Probiotics and Synbiotics in Intestinal Chronic Diseases. Nutrients. 2017;9(6):555.

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Published

2026-10-27

How to Cite

Shahzad, M., Aldughaythir, M. S., Alanazi, F., Alanazi, A., Alghamdi, M., Alharbi, H., Alsubaie, S., Alshabanah, L., & Almohrij, J. (2026). Probiotics in pediatric cardiac surgery: biological effects and clinical outcomes – a systematic review of randomized evidence. International Journal of Contemporary Pediatrics, 13(11), 2322–2329. https://doi.org/10.18203/2349-3291.ijcp20263822

Issue

Section

Systematic Reviews