Fecal carriage of multidrug-resistant organisms increases the risk of hepatic encephalopathy in patients with cirrhosis: insights from gut microbiota and metabolite features.

Abstract

Background: The impact of the fecal multidrug-resistant organism (MDRO) carriage on the gut microbiota, metabolite alterations, and cirrhosis-related complications remains unclear.

Methods: Eighty-eight patients with cirrhosis and 22 healthy volunteers were analyzed for plasma metabolites, fecal MDROs, and microbiota composition. The fecal bacterial and fungal composition was assessed using 16S ribosomal RNA and internal transcribed spacer sequencing, whereas plasma metabolomic analysis was evaluated via untargeted liquid chromatography-mass spectrometry. Predictors of cirrhosis-related outcomes, risk factors for MDRO carriage, and microbiota-metabolite correlations were analyzed.

Results: Fecal MDRO carriage was detected in 33% of patients with cirrhosis. MDRO carriers had a higher risk of hepatic encephalopathy (HE) compared to non-carriers (20.7% vs. 3.2%, p = 0.008). Patients carrying MDROs had higher plasma lipopolysaccharide (LPS) levels, and both elevated LPS and MDRO carriage independently predicted HE occurrence within 1 year. Compared with non-carriers, MDRO carriers had higher fecal bacterial and fungal burdens and exhibited different gut microbiota compositions, characterized by increased Streptococcus salivarius and enrichment of Saccharomycetes and Candida albicans. Thirty-one metabolites differed significantly among healthy controls, and patients with cirrhosis, with and without MDRO carriage. Six metabolites were significantly correlated with specific microbial taxa in MDRO carriers. Isoaustin, a fungal-derived metabolite, was significantly elevated in MDRO carriers with HE.

Conclusions: Fecal MDRO carriage was associated with endotoxemia, altered gut microbiota, metabolic changes, and a higher risk of HE. It's worthy to monitor fecal MDRO colonization in cirrhosis.