Rifaximin Plus Probiotics Reshape Gut Microbiota, Serum Propionate, and Mucosal Immunity in Cirrhosis-Related Hepatic Encephalopathy Microbiota-Immune Remodeling in HE.

backgroundHepatic encephalopathy (HE) remains a major cause of hospitalization and readmission in cirrhosis and is closely linked to hyperammonemia, microbial dysbiosis, impaired short-chain fatty acid (SCFA) output, barrier dysfunction, and altered mucosal immunity. We evaluated whether adding a multistrain probiotic to rifaximin was associated with greater neurometabolic improvement and coordinated gut-liver-brain axis changes.

methodsIn this prospective, 6-month, randomized, open-label, assessor-blinded, three-arm controlled study, 61 adults with cirrhosis-related HE received standard care alone (Con, n = 20), standard care plus rifaximin 550 mg twice daily (Rif, n = 20), or rifaximin plus a multistrain probiotic (1 × 10^9 CFU three times daily; Rif + Pro, n = 21). The main prespecified biochemical readout was serum ammonia at Month 6. A composite HE index incorporating mental status, flapping tremor, number connection test, and ammonia grade was analyzed as a prespecified exploratory neurometabolic score. A predefined mechanistic subset underwent 16S rRNA microbiome profiling, serum SCFA measurement, and fecal secretory IgA (SIgA) testing.

resultsBaseline characteristics did not differ across arms. Post-treatment serum ammonia decreased in a graded pattern (Con 177 ± 43.2, Rif 143 ± 37.5, Rif + Pro 117 ± 34.3 μmol/L), with parallel improvement in the exploratory HE index (10.0 ± 4.9, 5.3 ± 4.7, and 3.7 ± 4.1, respectively). In the mechanistic subset, the microbial community structure differed by treatment (PERMANOVA p = 0.006). Rif + Pro was associated with higher serum propionate, increased Lactobacillus salivarius-associated signal, reduced Bacteroides ovatus-associated signal, and marked fecal SIgA elevation compared with standard care or rifaximin alone. The SIgA-propionate relationship was interpreted as exploratory.

conclusionsRifaximin plus multistrain probiotics was associated with greater improvement in serum ammonia and exploratory HE severity readouts than rifaximin alone, accompanied by coordinated microbial, metabolic, and mucosal immune changes. These findings support confirmation in adequately powered event-driven trials with strain-resolved profiling and targeted metabolomics.