Gut microbiome is associated to different stages of liver disease and cognitive impairment

Liver disease is associated with significant alterations in gut microbiome (GM) potentially influencing cognition. This association is particularly evident in minimal hepatic encephalopathy (MHE), a common neuropsychiatric syndrome in liver disease. Our aim was to characterize microbiome changes in different stages of liver disease and cognitive function, with a particular focus on the early stages of both conditions. We sought to identify microbial patterns associated with liver disease stage and cognitive impairment. The study included 113 participants divided into five subgroups: healthy controls, patients with metabolic dysfunction-associated steatotic liver disease without or with mild cognitive impairment, cirrhotic patients without MHE, and cirrhotic patients with MHE. Microbiome analysis assessed taxonomic and functional aspects across these groups, along with biomarkers associated to cognitive impairment. Liver disease severity was associated with reduced GM diversity independently of cognitive status and correlated with a decline in beneficial autochthonous bacteria. Cognitive impairment was not linked to microbiota variations but rather to specific bacterial metabolic functions, such as tryptophan and glutamate degradation, which were associated with CXCL13 plasma levels and potential neuroinflammation. Finally, our research has shown that in this disease, describing a balanced production of the different fecal short-chain fatty acids is more relevant than individual concentrations. These findings suggest that the stage of liver disease impacts on microbiome-derived functions, a likely consequence of the influence of liver damage on gut microbial dynamics, which may be linked to the observed effects on cognition.