microbiota in cirrhosis

Decompensated liver cirrhosis (dLC) is associated with intestinal dysbiosis, however, underlying reasons and clinical consequences remain largely unexplored. We investigated bacterial and fungal microbiota, their relation with gut barrier integrity, inflammation and cirrhosis-specific complications in dLC-patients. Competing-risk analyses were performed to investigate clinical outcomes within 90 days. Samples were collected prospectively from 95 dLC-patients between 2017-2022. Quantitative metagenomic analyses clustered patients into three groups (G1-G3) showing greatly distinct microbial patterns. G1 (n=39) displayed lowest diversity and highest Enterococcus abundance, G2 (n=24) was dominated by Bifidobacteria, G3 (n=29) was most diverse and clustered most closely with healthy controls (HC). Of note, bacterial concentrations were significantly lower in cirrhosis compared with HC, especially for G1 that also showed lowest capacity to produce short chain fatty acids and secondary bile acids. Consequently, fungal overgrowth, dominated by Candida spp (51.63%), was observed in G1. Moreover, G1-patients most frequently received antibiotics (n=33; 86.8%), had highest plasma levels of Zonulin (p=0.044), sCD163 (p=0.019), a proinflammatory cytokine profile and numerically higher incidences of subsequent infections (p=0.09). In conclusion, distinct bacterial clusters were observed at qualitative and quantitative levels and correlated with fungal abundances. Antibiotics contributed to dysbiosis, which translated into intestinal barrier impairment and systemic inflammation.