Efficacy of Bacillus clausii as an adjuvant therapy in pathological neonatal unconjugated hyperbilirubinemia in the Nile Delta region of Egypt: a randomized controlled trial.

2026-06-11
Journal of tropical pediatrics 72(4)
- Samah S M Hussein
- Sahar M El-Haggar
- Sahar K Hegazy
- Mohamed A Rowisha

PubMed: 42378553
DOI: 10.1093/tropej/fmag047

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 22
Population: 44 neonates with confirmed pathological unconjugated hyperbilirubinemia
Methods: Randomized, parallel-group comparative study; phototherapy alone vs phototherapy plus oral Bacillus clausii probiotic
Funding: Unclear

Neonatal jaundice (NJ) is a common condition that may progress to serious complications such as kernicterus. Probiotics can also be used for treatment of jaundice by their effect on intestinal motility and microbial flora of the intestine. We aimed to evaluate the effect of probiotic supplementation as an adjuvant therapy in pathological neonatal unconjugated hyperbilirubinemia. A randomized, parallel-group comparative study was conducted on 44 neonates with confirmed pathological unconjugated hyperbilirubinemia admitted to the Neonatal Intensive Care Unit at Tanta University Hospital (Egypt) between May 2024 and April 2025. Participants were randomized (1:1) into two groups: phototherapy alone (control group n = 22) and phototherapy plus oral Bacillus clausii probiotic (probiotic group n = 22). Demographic data and bilirubin fractions were recorded. The primary outcome was the change in bilirubin levels; secondary outcomes included inflammatory biomarkers. Baseline characteristics were comparable between groups. Both groups exhibited significant declines in total serum bilirubin and indirect bilirubin, but only the probiotic group showed a significant reduction in direct bilirubin. By the end of treatment, the probiotic group showed a significantly greater reduction in lipopolysaccharide and tumor necrosis factor-α levels compared with the control group. Hospital stay was significantly shorter with probiotic therapy (3.8 ± 1.18 vs 6.3 ± 2.14 days; P < .001). Bacillus clausii supplementation alongside phototherapy significantly enhanced bilirubin reduction, decreased inflammatory markers, and shortened hospitalization, supporting its role as a beneficial adjunct therapy in neonatal hyperbilirubinemia.

Research Insights

Bacillus clausii→Reduced Direct Bilirubin Level
Both groups exhibited significant declines in total serum bilirubin and indirect bilirubin, but only the probiotic group showed a significant reduction in direct bilirubin.
Effect
Neutral
Effect size
Small
Bacillus clausii→Reduced Hospital Stay
Hospital stay was significantly shorter with probiotic therapy (3.8 ± 1.18 vs 6.3 ± 2.14 days; P < .001).
Effect
Beneficial
Effect size
Large
Bacillus clausii→Reduced Hospital Stay Duration
Hospital stay was significantly shorter with probiotic therapy (3.8 ± 1.18 vs 6.3 ± 2.14 days; P < .001)
Effect
Beneficial
Effect size
Large
Bacillus clausii→Reduced Indirect Bilirubin Level
Both groups exhibited significant declines in total serum bilirubin and indirect bilirubin, but only the probiotic group showed a significant reduction in direct bilirubin.
Effect
Neutral
Effect size
Small
Bacillus clausii→Reduced Lipopolysaccharide Level
By the end of treatment, the probiotic group showed a significantly greater reduction in lipopolysaccharide and tumor necrosis factor-α levels compared with the control group.
Effect
Beneficial
Effect size
Small
Bacillus clausii→Reduced Total Bilirubin Level
Both groups exhibited significant declines in total serum bilirubin and indirect bilirubin, but only the probiotic group showed a significant reduction in direct bilirubin.
Effect
Neutral
Effect size
Small
Bacillus clausii→Reduced Tumor Necrosis Factor Alpha
By the end of treatment, the probiotic group showed a significantly greater reduction in lipopolysaccharide and tumor necrosis factor-α levels compared with the control group.
Effect
Beneficial
Effect size
Small