Intestinal dysbacteriosis contributes to persistent cognitive impairment after resolution of acute liver failure.

Regulating the gut microbiota alleviates hepatic encephalopathy (HE). It remains unclear whether it is imperative to withhold treatment for microbial imbalance after liver functional recovery. This work aims to elucidate the alterations in cognitive behavior, liver function, synaptic transmission, and brain metabolites in acute liver failure(ALF) mice before and after hepatic function recovery. Here, thioacetamide was injected intraperitoneally to establish an ALF mouse model, which induced HE. By performing hierarchical clustering analysis, we found that the liver functions normalized, but cognitive dysfunction and intestinal dysbacteriosis were found in the ALF mice 14 days after thioacetamide injection. Additionally, fecal microbiota transplant from the ALF mice with liver function recovery could induce liver injury and cognitive impairment. Moreover, we found alterations in synaptic transmission in the ALF mice with liver function improvement, and the correlations between the gut bacteria and synaptic transmission in the cortex were significant. Finally, we detected apparent alterations in the brain metabolic profiles of the ALF mice after liver function improvement by performing 1 H nuclear magnetic resonance spectroscopy, suggesting a risk of HE. These results showed that intestinal dysbacteriosis in ALF mice with liver function recovery is sufficient to induce liver injury and cognitive impairment. These results indicated continuous care may be necessary for monitoring microbial imbalance even in ALF-induced HE patients whose liver function has recovered significantly.