Microbiota composition and intestinal barrier function modulated by tamsulosin and Lactococcus lactis in a cirrhosis rat model.

Abstract

Introduction: The pathological progression of cirrhosis disrupts the gut-liver axis. Lactococcus lactis (L. lactis) exhibits immunomodulatory properties and an ability to enhance intestinal barrier function. It has been demonstrated that tamsulosin has antifibrotic and anti-inflammatory effects in hepatic injury models. This study evaluated the effect of a tamsulosin and L. lactis co-treatment on the recovery of microbiota and intestinal barrier integrity in a Wistar rat liver cirrhosis model.

Material and methods: Male Wistar rats were administered CCl₄ intraperitoneally for 4 weeks. Subsequently, rats received tamsulosin, L. lactis, or both, orally for 2 weeks. The intestinal microbiota was assessed using 16S rRNA gene sequencing. Intestinal barrier integrity was evaluated using qPCR and Western blot for proteins ZO-1, occludin, and claudin-2. Bacterial translocation was evaluated by endotoxin concentration, bacterial DNA, and microbial culture of extraintestinal tissues. Finally, hepatic, intestinal histology, and liver function markers were analyzed.

Results: L. lactis and its combination with tamsulosin (T/L. lactis) increased microbial diversity and promoted a balanced gut microbiota characterized by a Firmicutes predominance followed by Proteobacteria and reduced Clostridia and Gammaproteobacteria levels. L. lactis group upregulated ZO-1 and occludin expression, while no significant changes were observed with tamsulosin or T/L. actis groups, nonetheless, intestinal morphology resembled that of healthy controls. Bacterial translocation analysis revealed no endotoxins, bacterial DNA, or bacteria in extraintestinal tissues. Both treatments also improved hepatic and intestinal histology, with partial liver function recovery.

Conclusión: Findings such as reduced bacterial translocation, lower systemic endotoxin levels, improved intestinal morphology, and modulation of gut microbiota composition suggest that both agents (L. lactis and tamsulosin), particularly in combination, exert positive effects on the intestinal barrier in cirrhosis.