Neurological dysfunction is improved after faecal microbiota transplantation in rats with bile duct ligated-induced chronic liver disease

Background: Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome arising from chronic liver disease (CLD). The gut microbiota has been shown to influence neurological functions via various mediators such as cytokines and/or bacterial metabolites. Faecal matter transplantation (FMT) in patients with cirrhosis has revealed beneficial effects on behaviour yet many limitations of these studies render the results inconclusive. Purpose: The aim of this study was to explore the impact of FMT on gut microbiota and neuro behaviour in bile-duct ligated (BDL) rats. Method: Male Sprague-Dawley rats were randomly assigned to one of 3 groups; SHAM, BDL-VEH (vehicle) and BDL-FMT (who received FMT daily from pooled feaces from 10 SHAM rats). After 5 weeks, behaviour tests were performed to evaluate short- and long-term memory, anxiety and motor coordination. Plasmatic parameters including cytokines, short chain fatty acids (SCFA) and liver biomarkers were measured. Finally, feaces were collected for bacterial sequencing and SCFA measurement. Results: BDL-VEH developed a loss of short- and long-term memory and motor coordination compared to SHAM rats. However, neurological dysfunction was prevented in the BDL-FMT group. FMT impacted microbiota composition as the genera Bifidobacterium, Lactobacillus and Akkermansia significantly increased in both BDL groups, while Provotellaceae UCO-001 significantly increased only in SHAM and BDL-FMT rats. Clostridium Senso Stricto 1 significantly increased only in BDL-VEH compared to SHAMs. Plasma pro-inflammatory cytokines (TNF-α & IL-1β) increased in both BDL groups compared to SHAM and no difference in anti-inflammatory cytokine IL-10 was noted. Analysis of SCFA in plasma and feaces showed significant changes in propionate between both BDL groups. Plasma propionate significantly positively correlated with behavioural results. Conclusion: Our results demonstrate that FMT leads to improvement in memory and motor coordination in BDL rats. The microbiota profile was different between BDL-VEH and SHAM whereas FMT led to further microbiota alterations. BDL-FMT led to a novel specific microbiota profile which in turn protected the brain. The protective effect of plasma propionate needs to be further explored to define its beneficial impact on the brain during chronic liver disease. Disclosure of Interest: None.