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Peer-reviewedCC BYnpj Biofilms and Microbiomes

Bifidobacterium animalis reshapes the bile acid pool and prevents neonatal jaundice: a clinical microbiome study from correlation to causation

5 more authors
8 affiliations
  1. 1Division of Neonatology, Longgang Central Hospital of Shenzhen, Shenzhen Clinical Medical College of Guangzhou University of Chinese Medicine
  2. 2Department of Neonatology, Affiliated Shenzhen Women and Children’s Hospital (Longgang) of Shantou University Medical College (Longgang District Maternity & Child Healthcare Hospital of Shenzhen City)
  3. 3Neonatal Medical Center, Children’s Hospital of Fudan University
  4. 4Center for Molecular Medicine, Children’s Hospital of Fudan University, National Center for Children’s Health
  5. 5Hunan Traditional Chinese Medical College
  6. 6Department of Pediatrics, South China Hospital of Shenzhen University
  7. 7Division of Neonatology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University
  8. 8Department of Neonatology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology)

Abstract

Neonatal jaundice (NJ) affects 60–80% of neonates, yet the underlying microbial mechanisms remain elucidated, despite known links between gut dysbiosis and bilirubin and bile acid (BA) metabolism. Through two-stage shotgun metagenomic-metabolomic analysis of 150 fecal samples from 120 neonates, we identified key taxa linked to bile acid (BA) metabolism in moderate-to-severe NJ. Furthermore, multi-omics integration revealed significant interkingdom correlations among gut phages, bacteria, and BAs. Dysbiosis featured enriched Streptococcus and Escherichia, depleted Bifidobacterium animalis, and group-specific phage signatures. In the independent clinical validation cohort, jaundice intervention normalized the dysbiotic profile, demonstrating significant suppression of pathogenic taxa concomitant with restoration of B. animalis abundance. In vitro, B. animalis subsp. lactis Y103-OTU5 remodeled BA via deconjugation. In a phenylhydrazine hydrochloride (PHZ)-induced murine model of hemolytic jaundice, oral administration of isolated B. animalis subsp. lactis Y103-OTU5 significantly attenuated hyperbilirubinemia and hepatic inflammation, likely via Cyp7a1/Cyp7b1-dependent modulation of BA synthesis and detoxification pathways. Structural equation modeling revealed a tripartite regulatory network: phages indirectly modulated BA through bacterial remodeling, while B. animalis directly regulated BA pathways, positioning it as a potential therapeutic candidate for hemolysis-associated neonatal jaundice. Collectively, these findings reveal a gut phage-bacteria-BA network in NJ, highlighting B. animalis as a therapeutic candidate with dual modulation of BA metabolism and phage-bacteria interactions.

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BibTeX
@article{chen2026bifidobacterium,
  title = {{Bifidobacterium animalis reshapes the bile acid pool and prevents neonatal jaundice: a clinical microbiome study from correlation to causation}},
  author = {Xianhong Chen and Cheng Chen and Peng Zhang and Xiaohong OuYang and Haiyan Ma and Wanling Chen and Tingting Li and Jing Han and Yanli Wang and Huijuan Wang and Qiujing Zhou and Guoqiang Cheng and Wei Zhou and Zhangbin Yu and Wenhao Zhou and Mingbang Wang and Shujuan Zeng},
  journal = {npj Biofilms and Microbiomes},
  year = {2026},
  month = jun,
  doi = {10.1038/s41522-026-01057-w},
  url = {https://doi.org/10.1038/s41522-026-01057-w},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Bifidobacterium animalis reshapes the bile acid pool and prevents neonatal jaundice: a clinical microbiome study from correlation to causation
AU  - Xianhong Chen
AU  - Cheng Chen
AU  - Peng Zhang
AU  - Xiaohong OuYang
AU  - Haiyan Ma
AU  - Wanling Chen
AU  - Tingting Li
AU  - Jing Han
AU  - Yanli Wang
AU  - Huijuan Wang
AU  - Qiujing Zhou
AU  - Guoqiang Cheng
AU  - Wei Zhou
AU  - Zhangbin Yu
AU  - Wenhao Zhou
AU  - Mingbang Wang
AU  - Shujuan Zeng
PY  - 2026
DA  - 2026/06/01
JO  - npj Biofilms and Microbiomes
DO  - 10.1038/s41522-026-01057-w
UR  - https://doi.org/10.1038/s41522-026-01057-w
AB  - Neonatal jaundice (NJ) affects 60–80% of neonates, yet the underlying microbial mechanisms remain elucidated, despite known links between gut dysbiosis and bilirubin and bile acid (BA) metabolism. Through two-stage shotgun metagenomic-metabolomic analysis of 150 fecal samples from 120 neonates, we identified key taxa linked to bile acid (BA) metabolism in moderate-to-severe NJ. Furthermore, multi-omics integration revealed significant interkingdom correlations among gut phages, bacteria, and BAs. Dysbiosis featured enriched Streptococcus and Escherichia, depleted Bifidobacterium animalis, and group-specific phage signatures. In the independent clinical validation cohort, jaundice intervention normalized the dysbiotic profile, demonstrating significant suppression of pathogenic taxa concomitant with restoration of B. animalis abundance. In vitro, B. animalis subsp. lactis Y103-OTU5 remodeled BA via deconjugation. In a phenylhydrazine hydrochloride (PHZ)-induced murine model of hemolytic jaundice, oral administration of isolated B. animalis subsp. lactis Y103-OTU5 significantly attenuated hyperbilirubinemia and hepatic inflammation, likely via Cyp7a1/Cyp7b1-dependent modulation of BA synthesis and detoxification pathways. Structural equation modeling revealed a tripartite regulatory network: phages indirectly modulated BA through bacterial remodeling, while B. animalis directly regulated BA pathways, positioning it as a potential therapeutic candidate for hemolysis-associated neonatal jaundice. Collectively, these findings reveal a gut phage-bacteria-BA network in NJ, highlighting B. animalis as a therapeutic candidate with dual modulation of BA metabolism and phage-bacteria interactions.
SN  - 2055-5008
ER  -