Synbiotic administration improves systemic and vascular alterations in rats with experimental microsurgical extrahepatic cholestasis: role of perivascular mesenteric innervation

Liver cholestasis is marked by bile acid accumulation in the liver, along with renal issues, portal hypertension, and altered circulation. Previous studies suggest that synbiotics may improve systemic and hemodynamic conditions in liver diseases. This study investigated the effects of a commercial synbiotic on gut microbiota, liver and kidney function, and vascular changes in a cholestatic rat model, focusing on nerve functions in the superior mesenteric arteries. Adult male Wistar rats were divided into three groups: Sham-operated, Cholestatic, and Cholestatic supplemented with a synbiotic for 3 weeks, following an initial 3-week postsurgical recovery period for model establishment. The synbiotic did not significantly alter gut microbiota composition, but reduced endotoxemia and increased butyric, acetic, and propionic acid levels. It improved, but did not fully reverse, liver and renal damage. In the synbiotic group, systolic blood pressure normalized to values similar to sham-operated animals, and mesenteric artery vasoconstriction increased in response to electric field stimulation. Although the vasomotor response to noradrenaline (NA) remained unchanged, NA release was higher (P < 0.05), indicating increased sympathetic activity due to symbiotic administration. Nitric oxide (NO) response did not change, but neuronal nitric oxide synthase (nNOS) expression and NO release increased after symbiotic supplementation (P < 0.05). Additionally, calcitonin gene-related peptide (CGRP) levels and function were reduced by synbiotics to control values (P < 0.05). In conclusion, synbiotic administration improved systemic, hepatic, renal, and vascular alterations associated with cholestasis in rats, suggesting that microbiota-directed therapies may represent a promising approach to mitigate complications of liver disease. • Liver pathologies are associated with systemic and vascular alterations. • Synbiotic supplementation reduced circulating endotoxin levels in experimental liver cholestasis. • Synbiotic treatment increased caecal short-chain fatty acid concentrations in cholestatic rats. • Liver and renal alterations in cholestasis were partially ameliorated by synbiotics. • Synbiotic administration modulated sympathetic, nitrergic and sensory components of mesenteric innervation.