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

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.
Funding Information
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030_173222/1)
  • European Commission (FP7-PEOPLE-2012-ITN project 316679 TRANSACT)
  • Fondation Leenaards
  • Louis-Jeantet Foundation
  • Centre Hospitalier Universitaire Vaudois
  • U.S. Department of Veterans Affairs (NIH R01 award (DK082435) and VA Merit award (BX002638), VA Career Development award (BX003486))
  • Hôpitaux Universitaires de Genève
  • Centre d'Imagerie BioMédicale