PROBIOTIC SUPPLEMENTATION IN NEONATAL JAUNDICE: CURRENT PERSPECTIVES AND THERAPEUTIC POTENTIAL
Abstract
Objective: The objective of this paper is to review the adjunctive role of probiotics in the treatment of neonatal jaundice (NJ), focusing on mechanisms, clinical trial evidence, and synergy with phototherapy.
Methods: Narrative synthesis of randomized controlled trials, mechanistic studies, and meta-analyses of probiotic interventions in term and preterm infants with hyperbilirubinemia.
Results: Probiotics, especially Saccharomyces boulardii and Bifidobacterium animalis subsp. lactis CP 9 enhance bilirubin clearance via gut modulation, decreased β glucuronidase activity, improved motility, and strengthened barrier integrity. Clinical trials report faster bilirubin decline, shorter phototherapy time, and better feeding tolerance. Multi-strain products also show positive outcomes, though variability in strains and dosing persists.
Conclusions: Probiotics are safe and effective adjuncts to phototherapy in treating NJ. Future standardized large RCTs with long-term follow-up are necessary to define precise clinical guidelines.
References
Serce O, Gursoy T, Ovali F, Karatekin G. Effects of Saccharomyces boulardii on neonatal hyperbilirubinemia: a randomized controlled trial. Am J Perinatol 2015;30(2)doi:10.1055s-0034-1376390
Nasief H, Alaifan MA, Tamur S et al. Phototherapy with/without probiotics in preterm neonates: randomized controlled trial. Paediatr Int Child Health 2024;44(1):24–29. PMID:38482867.
Hu D, Wang Y, Yang S, Zhang H. S. boulardii & phototherapy in preterm infants. J Pediatr (Rio J) 2023;99(3):263–268. PMID:36574954.
Tang W, Lu HY, Sun Q, Xu WM. S. boulardii + phototherapy RCT. Zhongguo Dang Dai Er Ke Za Zhi 2020;22(11):1149–1153. PMID:33172546.
Eghbalian F, Sabzehei MK, Talesh ST et al. Probiotic + phototherapy in term neonates: randomized controlled trial. Curr Pediatr Rev 2024;21(1):85–90. PMID:37929736.
Santosa I, Shoji H, Itoh S, Shimizu T. Roles of probiotics in reduction of neonatal jaundice in term newborns. Juntendo Iji Zasshi 2022;68(2):140–146. PMID:38912278.
Qian X, Zhao Y. Blue-light + probiotics RCT in pathological neonatal jaundice. Minerva Pediatr (Torino) 2024;76(1):133–135. PMID:37427960.
Rezki D, Firmansyah I, Darussalam D et al. Lactobacillus reuteri with phototherapy. Paediatrica Indonesiana 2023;63:219–225. doi:10.14238/pi63.4.2023.219-25. PMID:38523836.
Wang Y, Yu X, Chen J. Effect of S. boulardii on neonatal hyperbilirubinemia. Chin J Pediatr 2020;58:112–117.
Yu QY, Feng L, Zhao Y. S. boulardii in neonatal jaundice: randomized controlled trial. World J Pediatr 2021;17:489–495.
Chen K, Yuan T. Microbiota and neonatal hyperbilirubinemia. Am J Transl Res 2020;12:7459–7474.
Deshmukh J, Deshmukh M, Patole S. Systematic review of probiotics: neonatal hyperbilirubinemia. J Matern Fetal Neonatal Med 2019;32:154–163. doi:10.1080/14767058.2017.1369520.
Goodarzi R, Saadat S, Arshadzadeh M et al. Probiotics in neonatal hyperbilirubinemia: randomized controlled trial. J Neonatal Nurs 2021;28:1–8.
Abbas P, Pujiati P, Mayangsari C et al. L. acidophilus/S. thermophilus/B. longum in neonatal jaundice. Sains Medika 2023;14:58.
Vanderhoof JA, Young RJ. Pediatric probiotics. In: Butler JM, editor. Gastroenterol Clin North Am 2005;34:451–463.
Frontiers in Pharmacology. Systematic review: probiotic safety in neonatal jaundice. Front Pharmacol 2017;8:432. doi:10.3389/fphar.2017.00432.
Walker-Pizarro N, Terán CG. Review: roles of L. reuteri and S. boulardii. J Clin Neonatol 2021;10:30.
Sarfarazi M, Vajdi M, Mohammadhoseini M et al. S. boulardii in neonates: hospitalization outcome. Immunopathol Persa 2022;8:e02. doi:10.34172/ipp.2022.02.
Jenabi E, Ensiyeh J, Eghbalian F et al. The effect of probiotics and phototherapy combined with phototherapy alone on bilirubin reduction in term neonates: randomized controlled trial. Res Square preprint 2022;rs-1387582/v1.
Bernstein A et al. Meta-analysis: probiotics and phototherapy – bilirubin reduction. Iron J Matern Fetal Neonatal Med 2024;89:2–11.
Hotta M, Ueda K, Ikehara S et al. Phototherapy and risk of developmental delay: the Japan Environment and Children’s Study. Eur J Pediatr 2023;182:2139–2149. doi:10.1007/s00431-022-04785-1.
Wang J, Guo G, Li A, Cai WQ, Wang X. Challenges of phototherapy for neonatal hyperbilirubinemia (Review). Exp Ther Med 2021;21(3):231. doi:10.3892/etm.2021.9662.
Le Pichon JB, Riordan SM, Watchko J, Shapiro SM. The neurological sequelae of neonatal hyperbilirubinemia: definitions, diagnosis and treatment of the kernicterus spectrum disorders (KSDs). Curr Pediatr Rev 2017;13(3):199–209. doi:10.2174/1573396313666170815100214.
Akagawa S, Akagawa Y, Yamanouchi S et al. Association of neonatal jaundice with gut dysbiosis characterized by decreased Bifidobacteriales. Metabolites 2021;11(12):887. doi:10.3390/metabo11120887.
Su H, Yang S, Chen S et al. What happens in the gut during the formation of neonatal jaundice—underhand manipulation of gut microbiota? Int J Mol Sci 2024;25:8582. doi:10.3390/ijms25168582.
Hall B, Levy S, Dufault-Thompson K et al. BilR is a gut microbial enzyme that reduces bilirubin to urobilinogen. Nat Microbiol 2024;9:173–184.
Hall B, Levy S, Dufault-Thompson K et al. Discovery of the gut microbial enzyme responsible for bilirubin reduction to urobilinogen. bioRxiv preprint 2023;2023.02.07.527579. doi:10.1101/2023.02.07.527579.
Views:
33
Downloads:
8
Copyright (c) 2025 Anna Zielińska, Agata Nowacka, Marika Gutowska , Zuzanna Tomaszewska, Julia Ciechanowicz, Aleksandra Przybylska, Stanisław Ciechanowicz, Piotr Kupidłowski, Adrianna Maria Perzanowska, Julia Dura

This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.