Probiotics improve the neurometabolic profile of rats with chronic cholestatic liver disease

Veronika Rackayová,Olivier Braissant,Emmanuelle Flatt,Cristina Cudalbu,Matthew McMillin,Valérie A McLin,Daniela Capobianco,Sharon DeMorrow,Paola Mastromarino,Jocelyn Grosse

doi:10.1038/s41598-021-81871-8

Abstract

Chronic liver disease leads to neuropsychiatric complications called hepatic encephalopathy (HE). Current treatments have some limitations in their efficacy and tolerability, emphasizing the need for alternative therapies. Modulation of gut bacterial flora using probiotics is emerging as a therapeutic alternative. However, knowledge about how probiotics influence brain metabolite changes during HE is missing. In the present study, we combined the advantages of ultra-high field in vivo 1H MRS with behavioural tests to analyse whether a long-term treatment with a multistrain probiotic mixture (VIVOMIXX) in a rat model of type C HE had a positive effect on behaviour and neurometabolic changes. We showed that the prophylactic administration of this probiotic formulation led to an increase in gut Bifidobacteria and attenuated changes in locomotor activity and neurometabolic profile in a rat model of type C HE. Both the performance in behavioural tests and the neurometabolic profile of BDL + probiotic rats were improved compared to the BDL group at week 8 post-BDL. They displayed a significantly lesser increase in brain Gln, a milder decrease in brain mIns and a smaller decrease in neurotransmitter Glu than untreated animals. The clinical implications of these findings are potentially far-reaching given that probiotics are generally safe and well-tolerated by patients.

Highlights

Chronic liver disease leads to neuropsychiatric complications called hepatic encephalopathy (HE)
We showed that prolonged administration of a multistrain probiotics mixture (VIVOMIXX) in a rat model of type C HE resulted in a milder course of HE compared to untreated animals
The administration of probiotics reduced plasma ammonium in bile duct ligation (BDL) rats and was associated with milder changes in the neurometabolic profile compared to BDL rats without probiotics

Summary

Introduction

Chronic liver disease leads to neuropsychiatric complications called hepatic encephalopathy (HE). Both the performance in behavioural tests and the neurometabolic profile of BDL + probiotic rats were improved compared to the BDL group at week 8 post-BDL. Dysbiosis and secondary intestinal inflammation[16,17,18] may lead to increased gut permeability, in turn leading to bacterial translocation[19,20] Together, this increases systemic inflammation[8,21] and further contributes to the progression of liver disease and its complications. Spontaneous bacterial peritonitis (SBP) and other infections[22,23], all of which are considered precipitating factors of HE

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Results

Conclusion