Conducted at the China Medical University Children’s Hospital between May 2019 and July 2023, the randomised double-blind study offered compelling evidence that two probiotic strains — Lactobacillus salivarius AP-32 and Bifidobacterium animalis subsp. lactis CP-9 — enhanced the efficiency of phototherapy and supported neonatal gut health.
This was the key finding from a clinical trial by researchers at Taiwan’s China Medical University and probiotics manufacturer Glac Biotech Co., Ltd.
Addressing a common yet serious condition in newborns
Neonatal jaundice affects up to 70% of infants in Western countries and even higher numbers among Asian populations.
While often a harmless physiological response, untreated cases can lead to severe complications, including brain damage caused by high bilirubin levels.
Phototherapy, the standard treatment, uses blue light to convert bilirubin into water-soluble forms that can be excreted.
However, this method can have side effects, including sleep disturbances, thermoregulatory issues, diarrhoea, and skin discolouration.
While phototherapy is effective, it has limitations and side effects. The clinical trial aimed to explore whether probiotics could support faster recovery and reduce reliance on prolonged phototherapy.
Testing probiotics as a phototherapy booster
The trial enrolled 300 full-term newborns with bilirubin levels above 15 mg/dL on the fourth day after birth.
Infants were randomly assigned to one of three groups: the first received L. salivarius AP-32, the second B. animalis subsp. lactis CP-9, and the third a placebo containing maltodextrin. Each probiotic capsule delivered five billion CFU (colony-forming units) and was administered twice daily until discharge.
All participants also received phototherapy under standardised conditions.
Both probiotic groups subsequently experienced faster declines in bilirubin levels and required shorter phototherapy sessions, compared to the placebo group.
Notably, the group that had received L. salivarius AP-32 saw a significant reduction in hospital stay — seven hours shorter than the placebo group.
At the same time, phototherapy duration was significantly shorter in both probiotic groups, and the cumulative light exposure was lower, reducing the potential risks associated with extended phototherapy sessions.
These findings suggested that probiotics could act as effective adjuvants to phototherapy, promoting faster clearance of bilirubin.
Improving gut microbiome diversity: A crucial secondary benefit
Beyond reducing phototherapy needs, probiotic supplementation had a notable impact on the gut microbiome.
Gut bacteria play a critical role in bilirubin metabolism by breaking down and eliminating waste products, and disruptions to this system can delay jaundice recovery.
Microbiome analysis showed a significant increase in gut microbial diversity in the L. salivarius AP-32 group, and an increased abundance of beneficial bacteria in both probiotics groups.
These strains didn’t just pass through the digestive tract but actively colonised the gut and promoted a healthier microbiome.
How probiotics enable quicker bilirubin expulsion
Probiotic bacteria contribute to reducing jaundice through several mechanisms. They promote bowel movements, helping expel bilirubin faster.
They also inhibit β-glucuronidase activity, which converts conjugated bilirubin back into its toxic unconjugated form.
Additionally, Lactobacillus strains improve intestinal lining integrity, reducing bilirubin leakage back into the bloodstream. Probiotics also increase the presence of bacteria that metabolise bilirubin efficiently.
These effects explain why the infants in the probiotic groups cleared bilirubin faster and needed less phototherapy.
No safety concerns observed
Crucially, no adverse reactions were reported during the trial. Probiotic supplementation was well tolerated, and there were no differences in adverse outcomes between groups.
This finding is important for clinicians concerned about the safety of probiotic use in vulnerable populations, as these strains could offer an effective, low-risk adjunct therapy for neonatal jaundice.
Study limitations and future directions
Despite the promising results, the researchers noted some limitations.
Firstly, the study did not account for differences in feeding methods (breastfeeding versus formula), which can influence gut microbiota and bilirubin metabolism.
Secondly, the researchers did not collect weight loss data, another important factor in jaundice outcomes.
Future research should focus on how feeding practices interact with probiotic efficacy.
Investigating the effects of additional probiotic strains and dosages could also help refine treatment protocols.
A promising step toward safer, faster jaundice management
The integration of Lactobacillus salivarius AP-32 and Bifidobacterium animalis CP-9 with standard phototherapy provides a promising strategy for treating neonatal jaundice.
This approach not only reduces treatment time but also enhances gut health, with no observed safety concerns.
The researchers concluded: “This combined therapy not only accelerates bilirubin reduction but also appears to do so without significant side effects. The potential to shorten the duration of jaundice through this synergistic treatment could have lasting benefits on the growth and development of affected infants, making it a valuable addition to current therapeutic strategies.”
Source: National Center for Biotechnology Information
“Effects of phototherapy combined with Lactobacillus salivarius AP-32 or Bifidobacterium animalis subsp. lactis CP-9 on improving neonatal jaundice and gut microbiome health: a randomized double-blind clinical study”
https://doi.org/10.1186/s12937-025-01126-4
Authors: Ming-Luen Tsai, et al.
