Rifaximin-induced changes in the gut microbiome associated to improvement of neurotransmission alterations and learning in rats with chronic liver disease

Rifaximin, a gut-targeted antibiotic, improves cognitive function and reduces the risk of hepatic encephalopathy (HE), yet its effects on the gut-brain axis remain unknown. This study explores how rifaximin influences gut microbiota functions and its association with cognitive function and molecular alterations in rats with liver injury. Liver injury was induced by chronic administration of carbon tetrachloride (CCl4), and rifaximin was administered daily. Fecal samples were collected after eight weeks of CCl4 administration, and taxonomic and functional changes in the gut microbiome were analyzed. Rifaximin altered microbiota diversity and composition, increasing α diversity in liver-injured rats but reducing diversity in healthy rats. It influenced microbiota interactions with neurotransmission alterations, where Dorea, Lachnospiraceae A2, and possibly Erysipelotricaceae might be important contributors. Functionally, butyric acid levels negatively correlated with gene orthologues associated with GABA, tryptophan, and glutamate degradation pathways. In healthy rats, fecal short-chain fatty acid (SCFA) levels were positively correlated with each other, a pattern absent in other groups. Rifaximin significantly influenced gut microbiota and promoted bacterial groups linked to improved cognition and neurotransmission in liver disease. Our findings underscored the direct relationship between a healthy microbiome and the maintenance of balanced SCFA concentrations.