# Hepato-ocular crosstalk: Bile acids bridging pathogenesis and therapy

**Authors:** Peng Wang, Jingchen Xie, Feng Xiang, Suhui Xiong, Yamei Li, Bohou Xia, Limei Lin, Qiuxian Peng

PMC · DOI: 10.1016/j.isci.2026.115118 · iScience · 2026-02-21

## TL;DR

This paper explores how bile acids connect liver and eye diseases, suggesting that restoring bile acid balance could treat both.

## Contribution

The paper introduces bile acid homeostasis as a unifying therapeutic framework for hepato-ocular comorbidities.

## Key findings

- Dysregulated bile acid metabolism links hepatic dysfunction with ocular pathology.
- Bile acid imbalance causes ocular injury through FXR and TGR5 signaling and immune activation.
- Targeting bile acid homeostasis offers therapeutic strategies for liver-eye diseases.

## Abstract

Bile acids, the major metabolites of cholesterol, function as pleiotropic signaling molecules beyond their classical role in lipid digestion. Increasing evidence indicates that dysregulated bile acid metabolism represents a shared molecular basis linking hepatic dysfunction with ocular pathology. Aberrations in bile acid synthesis, transport, and signaling lead to bile acid imbalance, which drives ocular injury through direct cytotoxicity, disruption of retinal and lens homeostasis mediated by FXR and TGR5 signaling, and immune activation along the gut-liver-eye axis. These mechanisms are implicated across a spectrum of conditions, ranging from inborn metabolic disorders to acquired cholestatic diseases. This review further highlights the translational potential of targeting bile acid homeostasis. We summarize emerging therapeutic strategies, including bile acid-based interventions, targeted drug delivery, and microbiome modulation, that aim to restore systemic bile acid balance. Collectively, we propose reconstruction of systemic bile acid homeostasis as a unifying therapeutic framework for hepato-ocular comorbidities.

Health sciences

## Linked entities

- **Proteins:** NR1H4 (nuclear receptor subfamily 1 group H member 4), GPBAR1 (G protein-coupled bile acid receptor 1)

## Full-text entities

- **Genes:** NR1H4 (nuclear receptor subfamily 1 group H member 4) [NCBI Gene 9971] {aka BAR, FXR, HRR-1, HRR1, PFIC5, RIP14}, GPBAR1 (G protein-coupled bile acid receptor 1) [NCBI Gene 151306] {aka BG37, GPCR19, GPR131, M-BAR, TGR5}
- **Diseases:** cholestatic diseases (MESH:D002779), inborn metabolic disorders (MESH:D020739), hepatic dysfunction (MESH:D008107), ocular injury (MESH:D005131), cytotoxicity (MESH:D064420)
- **Chemicals:** Bile acids (MESH:D001647), lipid (MESH:D008055), cholesterol (MESH:D002784)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12992499/full.md

## References

113 references — full list in the complete paper: https://tomesphere.com/paper/PMC12992499/full.md

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Source: https://tomesphere.com/paper/PMC12992499