Influence of beta-blockers on the gut microbiome and metabolic profile in liver cirrhosis by sex

Introduction Beta-blockers (BB) are used in liver cirrhosis to manage portal hypertension and variceal bleeding. Evidence suggests benefits on systemic inflammation. Their impact on the gut microbiome remains poorly understood. We aim to investigate the effects of BB on the gut microbiome and metabolome in patients with liver cirrhosis, focusing on sex-specific differences.

Material and Methods 121 patients with liver cirrhosis were recruited. MELD scores were available for all, stool samples of 99, and 16S rRNA sequencing data of 84 patients (62 men; 22 women). Patients were grouped by sex and compared across non-selective beta-blockers (NSBB), selective beta-blockers (SBB), and no intake. Alpha- and beta-diversity, and ANCOM and LEfSe, were employed to analyze the microbiome. The metabolome was assessed using NMR and orthoPLS-DA.

Results 40 patients took NSBB (11 women), and 22 SBB (4 women). In men, MELD scores were lower for SBB users compared to NSBB (p=0.031). Microbiome analysis revealed increased alpha diversity in male SBB users compared to NSBB users (p<0.05). ANCOM and LEfSe identified a higher abundance of short-chain fatty acid (SCFA) producers, Prevotella and Phascolarctobacterium, in NSBB and SBB users. In women, SCFA producers UCG-002 and Subdoligranulum were more abundant in non-BB users, Ruminococcaceae Incertae Sedis was higher in SBB users. In the metabolome, l-valine was associated with male non-BB users. Hypoxanthine was elevated in BB users, particularly SBB. In women, hypoxanthine was linked to BB intake, indicating shared metabolomic responses across sexes (VIP≥2.5).

Conclusion BB use in liver cirrhosis patients induces microbiome and metabolome changes with sex-specific differences. In men, SBB intake was linked to lower MELD scores, increased diversity, and beneficial bacteria. In women, beneficial bacteria were increased in non-BB users. Metabolome analysis revealed fewer sex-specific differences, with both sexes showing increased hypoxanthine, which was associated with improved gut permeability and Prevotella abundance

Publication History

Article published online:
13 May 2025