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.

2021 ISHEN guidelines on animal models of hepatic encephalopathy

“…Ornithine‐phenylacetate (OP) and liposome‐supported peritoneal dialysis have also shown to be beneficial in lowering blood ammonia levels in BDL rats 128,129 . The probiotic VIVOMIXX has been recently shown to attenuate hyperammonemia and improve both the performance in behavioural tests and the neurometabolic profile of BDL treated rats 130 . OP has also been shown to lower blood ammonia in rats with portal‐caval anastomosis 123 .…”

Brain imaging in children with neonatal cholestatic liver disease: A systematic review

“…For those with stable chronic liver disease, glutamate/glutamine to creatine was high and consistent with subclinical encephalopathy, similar to what is seen in animal models. Rats with bile duct ligation showed increased glutamine decreased glutamate and myo-inositol levels, 105,106 and rats with bile duct ligation early in life had additional molecular changes, including higher glutamine levels in the brain, compared with rats undergoing bile duct ligation later in life, suggesting that the developing brain has a unique vulnerability to chronic cholestatic liver disease. 106 However, the children who underwent LTX also had increased glutamate/glutamine to creatinine, but it was lower than in stable liver disease.…”

Neurometabolism and brain morphometry in an adolescent female with an extra‐hepatic congenital portosystemic shunt

“…Classically, it is held from high magnetic field spectroscopy studies in animals that administration of ammonium is associated with a rapid and linear increase in brain glutamine. 11 In type C HE animal models 15 , 16 , 28 , 29 , 30 and CPSS mice, 31 the Gln increase generates an osmolarity change in the brain, which in turn releases the main brain osmolytes (Ins, Tau, tCho) to counter the osmotic load. 15 , 18 These findings have been also observed in humans with type C HE.…”