A liver transplant improves the intestinal microbiota and its functions

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A liver transplant in a cirrhotic patient brings about a significant reduction in the intestinal dysbiosis that accompanies the disease, including a greater abundance of commensal bacteria populations and an improvement in many organic functions that are correlated with their presence.

 

A liver transplant is a last resort intervention in cases of advanced cirrhosis. Firstly, it improves the vital prognosis, and secondly it allows the intestinal microbiota that has been disrupted by the disease to return to equilibrium. This recent discovery drove an international team to characterize the intestinal microbiota before and after transplant.

Parameters studied

To this end, the researchers tracked changes in certain functionalities linked to bacterial populations which are classically impaired in cirrhosis cases: a lower level of conversion of primary bile acids, reduced production of microbial-mammalian co-metabolites such as trimethylamine oxide or endotoxemia, inflammation and hyperammonemia, all three of which are signs of hepatic encephalopathy. A cohort of 40 cirrhosis patients (with an average age of 56 years) were tested prior to liver transplant, and between 4 to 10 months after. The collection of stool samples allowed for the identification of bacterial populations and a bile acid assay.  Serum and urine samples were used to characterize endotoxins, lipids and metabolites. Finally, encephalopathy was assessed by a cognitive test.

Restoration of the physiology and the microbiota

Despite the difficulties associated with post-transplant immunosuppressive treatment, the results teach us that liver transplant is accompanied, first of all, by a clear improvement in the intestinal microbiota, with increased diversity and abundance of commensal bacteria (Ruminococcaceae and Lachnospiraceae) at the expense of pathogenic bacteria (Enterobacteriaceae of the genera Escherichia, Shigella, Salmonella…). Above and beyond the reduction in infection risks linked to the depletion of Gram-negative bacteria, the physiological impact of this new microbiota was observed at all levels studied: an increase in bile acid conversion and co-metabolite production was observed, in addition to a reduction in serum ammonium and improvement in the types of circulating lipids (diacylglycerols, cholesterol esters, phosphoethanolamine, sphingomyelin…). All elements which contribute to the preservation/restoration of health and cognitive capacity, as proven by dedicated tests (Psychometric Hepatic Encephalopathy Test Score [PHES]). A liver transplant, not followed by complications, therefore has a beneficial effect on the intestinal microbiota and its functions, highlighting the role of the liver in the definition of local bacterial populations.

 

Sources:

J. Bajaj, G. Kakiyama, J. Cox2, et al. Alterations in Gut Microbial Function Following Liver Transplant, Accepted Article, doi: 10.1002/lt.25046