Hyperammonemia reduces beneficial lactobacilli and bifidobacteria populations disrupting the metabolic balance of the gut microbiome in rats

The gut microbiome significantly impacts health conditions, including neurological diseases, and is highly sensitive to dietary and environmental changes. Hyperammonemia (HA) is a major contributor to hepatic encephalopathy (HE). Although dysbiosis associated with HA has been reported, its possible physiological connection with HE conditions remains unclear. In this study, chronic HA was induced by feeding rats with an ammonia-enriched diet (30 percent ammonia acetate) to evaluate the changes generated in the gut microbiome. Next-generation sequencing (NGS) and bioinformatics methods were used to compare fecal microbiota 16S rDNA profiles in rats after four weeks of HA diet with control rats fed with a standard diet. Significant differences were found alpha diversity of the microbiota. Beta diversity also showed a clear clustering of the taxonomic distribution between control samples and HA rats. Correlation analyses revealed that genera belonging to the Lachnospiraceae family and Alistipes were associated with the HA group, whereas lactic acid-producing and xylanolytic Firmicutes were reduced. Indeed, the genus Alistipes was identified as the keystone group in the HA samples. Notably, these changes resulted in significant alterations to the metabolic potential of HA rats microbiome, as evidenced by the reduction in key pathways related to the pyruvate dehydrogenase complex, sucrose, 4-aminobutyrate (GABA) and urea degradation. Decreased concentrations of acetic acid and butyric acid in feces supported these predicted metabolic changes. These results demonstrate that HA contributes to microbiome changes associated with metabolic, immune and neurological changes that lead to HE disease.