Daucus carota-derived extracellular vesicles lowers ammonia and improves lysine–butanoate metabolism in animal model of hepatic encephalopathy

Hepatic encephalopathy (HE) is a debilitating complication of chronic liver disease driven by hyperammonemia, gut dysbiosis, and disrupted nitrogen metabolism. Current therapies reduce ammonia but inadequately restore microbial metabolic homeostasis. Here, we investigated the edible plant-derived extracellular vesicles (PDEVs) that could modulate gut microbial metabolism and ameliorate HE. PDEVs from different plant sources were evaluated in a thioacetamide (TAA)-induced rat model of HE, wherein black carrot i.e Daucus carota subsp. sativus -derived extracellular vesicles (DC-EVs) most effectively reduced plasma ammonia, improved liver injury and sensorimotor functions. DC-EVs induced a shift in gut microbiome, as characterized by reduction in Escherichia–Shigella and enrichment of Corynebacterium , Lachnoclostridium and increased fecal L-lysine and butyryl-CoA levels. Notably, Corynebacterium abundance correlated positively with L-lysine and inversely with circulating ammonia. Functional biological effects and DC-EV-cargo analysis further supported a link between DC-EVs, microbial lysine metabolism, and enhanced ammonia utilization. Hence, these findings identified DC-EVs as promising prophylactic therapy for HE that can modulate microbial nitrogen metabolism and mitigate hyperammonemia.