# Bilirubin-microbiota interaction: molecular mechanisms and therapeutic strategies in neonatal jaundice

**Authors:** Wenlong Yan, Ning Du, Kun Zhang, Pingping Yang, Jing Guo, Lingfen Xu

PMC · DOI: 10.3389/fmicb.2025.1749152 · 2026-01-13

## TL;DR

This paper explores how bilirubin and gut bacteria interact, influencing bilirubin metabolism and offering potential new treatments for neonatal jaundice.

## Contribution

The paper provides a synthesis of recent findings on the bidirectional interaction between bilirubin and the gut microbiota in neonatal jaundice.

## Key findings

- Bilirubin exerts selective pressure on gut microbial communities based on its concentration.
- The gut microbiota influences bilirubin metabolism through pH changes and enzyme production.
- Modulating the microbiota may help manage bilirubin levels and reduce toxicity in neonates.

## Abstract

Recent studies have revealed a complex interplay between bilirubin metabolism and the gut microbiota. Bilirubin functions as a potent antioxidant and signaling molecule in humans, and its concentration-dependent effects on distinct microbial taxa indicate that the compound exerts selective pressure on the gut ecosystem. The gut microbiota modulates bilirubin metabolism by altering intestinal pH, producing and activating Bilirubin metabolic enzyme, and bile acids. Because perturbations in bilirubin handling are especially common—and potentially neurotoxic—in neonates, a concise synthesis of recent progress is warranted. Here we review how microbial communities reshape bilirubin flux, how bilirubin and its conjugates, in turn, sculpt microbial ecology, and how the dynamic equilibrium between conjugated and unconjugated bilirubin in hyperbilirubinaemia is influenced by the microbiome. Regulating gut microbiota to accelerate bilirubin clearance or attenuate its toxicity may therefore offer a tractable therapeutic avenue.

## Linked entities

- **Chemicals:** bilirubin (PubChem CID 5280352)

## Full-text entities

- **Diseases:** toxicity (MESH:D064420), neurotoxic (MESH:D020258), neonatal jaundice (MESH:D007567)
- **Chemicals:** bile acids (MESH:D001647), Bilirubin (MESH:D001663)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12845330/full.md

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Source: https://tomesphere.com/paper/PMC12845330