Liver transplant modulates gut microbial dysbiosis and cognitive function in cirrhosis

Liver transplant (LT) improves daily function and cognition in cirrhosis but a subset can remain impaired. Unfavorable microbiota or dysbiosis is observed in cirrhosis but the effect of LT on microbial composition; especially with poor post-LT cognition, is unclear. Aims: (1) determine the effect of LT on gut microbiota and (b) to determine whether gut microbiota are associated with cognitive dysfunction post-LT. We enrolled outpatient cirrhotics on the LT list and followed them till 6 months post-LT. Cognition (Psychometric hepatic encephalopathy score, PHES), quality of life (HRQOL) and stool microbiota (multi-tagged sequencing for diversity and taxa) was performed at both visits. Persistent cognitive impairment was defined as a stable/worsening PHES. Both pre/post-LT data were compared with age-matched healthy controls. We enrolled 45 patients (56±7 years, MELD 26±8). They received LT 6±3 months after enrollment and were re-evaluated 7±2 months post-LT with a stable course. A significantly improved HRQOL, PHES, with increase in microbial diversity, increase in autochthonous and decrease in potentially pathogenic taxa, were seen post-LT compared to baseline. However, there was continued dysbiosis and HRQOL/cognitive impairment post-LT compared to controls in 29% who did not improve PHES post-LT. In these, Proteobacteria relative abundance was significantly higher and Firmicutes were lower post-LT while the reverse occurred in the group that improved. Delta PHES was negatively correlated with delta Proteobacteria and positively with delta Firmicutes. Conclusions: LT improves gut microbiota diversity and dysbiosis compared to pre-LT baseline but residual dysbiosis remains compared to controls. There is cognitive and HRQOL enhancement in general post-LT but a higher Proteobacteria relative abundance change is associated with post-transplant cognitive impairment. This article is protected by copyright. All rights reserved.