Study on the correlation between circadian rhythm, intestinal flora and Liver stiffness in patients with Hepatic fibrosis

Background: Hepatic fibrosis (HF) is a critical pathological process in chronic liver diseases, and its progression is closely associated with gut microbiota dysbiosis and circadian rhythm disruption. However, the interplay between these factors in HF remains poorly understood. This study aimed to investigate the relationship between gut microbiota composition, circadian rhythm disturbances, and HF, providing new insights into potential therapeutic strategies. Methods: A cross-sectional study was conducted, enrolling patients with HF and healthy controls. Liver stiffness measurement (LSM) was assessed using transient elastography. Circadian rhythm status was evaluated with the Morningness-Eveningness Questionnaire-5 (MEQ-5). Gut microbiota composition was analyzed via 16S rRNA sequencing, and differences in microbial diversity and taxa abundance were compared between groups. Correlation analyses were performed to explore the associations between gut microbiota, LSM, and circadian rhythm. Results: Patients with HF exhibited significant alterations in gut microbiota composition at both the phylum and genus levels ( p <0.05, r = − 0.244). The relative abundances of Escherichia-Shigella, Klebsiella, Pseudomonadota, Ruminococcus gnavus group , and Enterocloster were significantly increased, while Dorea, Holdemanella, [Ruminococcus] gauvreauii group, [Eubacterium] ventriosum group, CAG-352 , and Marvinbryantia were markedly decreased. These microbial shifts were associated with enhanced intestinal inflammation and hepatic immune activation. Notably, Escherichia-Shigella may contribute to HF progression via LPS-TLR4/inflammasome activation, inflammatory cytokine release, and reduced short-chain fatty acid (SCFA) production. Conversely, SCFA-producing bacteria in the Firmicutes phylum showed a potential protective role by mitigating hepatic inflammation and lipid accumulation. Furthermore, circadian rhythm disruption was negatively correlated with LSM, and an increased abundance of Mediterraneibacter was observed in patients with circadian rhythm disturbances. As Mediterraneibacter is known to produce ethanol, its elevated levels may exacerbate hepatic injury and inflammation, potentially contributing to HF development. Conclusion: This study reveals a significant association between gut microbiota dysbiosis, circadian rhythm disruption, and HF severity. Our findings suggest that circadian rhythm disturbances may influence HF progression by modulating gut microbiota composition and metabolic activity. These insights highlight potential therapeutic strategies, including circadian rhythm modulation (e.g., light therapy, timed medication) and gut microbiota-targeted interventions, to slow or reverse HF progression.