In this commentary, we discuss new findings indicating that microbiota transplantation has favorable impact on portal hypertension (PH) in the experimental model of cirrhosis induced by bile duct ligation (BDL) (Huang et al.; Clin Sci (Lond) (2021) 135(24): 2709–2728, doi: 10.1042/CS20210602). Sinusoidal PH is an ominous outcome of advanced chronic liver disease, characterized by increased intrahepatic vascular resistance (IHVR), splanchnic hyperemia, and the development of portosystemic collaterals. In the work of Huang et al., microbiota transplantation not only alleviated splanchnic hyperdynamic circulation by improving vascular responsiveness and decreasing mesenteric angiogenesis, but also reduced blood flow in portosystemic collaterals. Surprisingly, however, microbiota transplantation had no effect on intrahepatic vasoconstriction in this experimental model. We discuss these observations in the context of recent literature showing that manipulation of the gut microbiota (either by transplantation or through the use of probiotics) may improve IHVR, which is one of the earliest abnormalities in the pathogenesis of sinusoidal PH. Further research is needed to explore the specific molecular and cellular targets associated with the correction of dysbiosis in liver disease.