Changes in metabolomic profile in dogs with hepatic encephalopathy secondary to congenital portosystemic shunt suggests mitochondrial homeostasis disturbances

OBJECTIVE: To identify specific metabolomic changes in dogs showing signs of hepatic encephalopathy (HE) compared to those not showing obvious neurological signs and to follow these changes following medical treatment.

METHODS: In this prospective observational study, we recruited 10 client-owned dogs diagnosed with congenital portosystemic shunt (from March 2021 through October 2022). The sera of dogs with or without signs of HE at the time of diagnosis of congenital portosystemic shunt and following medical treatment for more than 4 weeks were analyzed by UPLC-MS.

RESULTS: Dogs showing signs of HE at the time of diagnosis (n = 6) had significantly lower serum concentrations of taurine (fold change [FC], 0.44), creatine (FC, 0.32), and guanine (FC, 0.45) and higher serum concentrations of 3-hydroxybenzaldehyde (FC, 2.51) than their counterparts not showing signs of HE (4). A marked albeit nonsignificant decrease in serum stearate concentrations was also observed in the HE group (FC, 0.12). Following medical treatment, which improved neurological signs, the concentrations of these metabolites, particularly taurine, normalized to concentrations similar to the non-HE group.

CONCLUSIONS: Dogs with HE exhibit a different serum metabolomic profile compared to dogs without signs of HE. The main changes are suggesting disturbances in mitochondrial homeostasis in dogs suffering from HE.

CLINICAL RELEVANCE: Supporting mitochondrial function could form the basis of new therapeutic strategies in HE and merits further investigations in future studies.