Liver transplant modulates gut microbial dysbiosis and cognitive function in cirrhosis

Jasmohan S. Bajaj, Andrew Fagan, Masoumeh Sikaroodi, Melanie B. White, Richard K. Sterling, HoChong Gilles, Douglas Heuman, Richard T. Stravitz, Scott C. Matherly, Mohammed S. Siddiqui, Puneet Puri, Arun J. Sanyal, Velimir Luketic, Binu John, Michael Fuchs, Vishwadeep Ahluwalia, Patrick M. Gillevet

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. (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. 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.