Gut-Liver Axis Dysregulation in Portal Hypertension: Emerging Frontiers

Abstract

Portal hypertension (PH) is a complex clinical challenge with severe complications, including variceal bleeding, ascites, hepatic encephalopathy, and hepatorenal syndrome. The gut microbiota (GM) and its interconnectedness with human health have emerged as a captivating field of research. This review explores the intricate connections between the gut and the liver, aiming to elucidate how alterations in GM, intestinal barrier function, and gut-derived molecules impact the development and progression of PH. A systematic literature search, following PRISMA guidelines, identified 12 original articles that suggest a relationship between GM, the gut-liver axis, and PH. Mechanisms such as dysbiosis, bacterial translocation, altered microbial structure, and inflammation appear to orchestrate this relationship. One notable study highlights the pivotal role of the farnesoid X receptor axis in regulating the interplay between the gut and liver and proposes it as a promising therapeutic target. Fecal transplantation experiments further emphasize the pathogenic significance of the GM in modulating liver maladies, including PH. Recent advancements in metagenomics and metabolomics have expanded our understanding of the GM's role in human ailments. The review suggests that addressing the unmet need of identifying gut-liver axis-related metabolic and molecular pathways holds potential for elucidating pathogenesis and directing novel therapeutic interventions.

Keywords: gut–liver axis; liver diseases; metabolomics; microbiome; portal hypertension.

Figure 1

Study selection flowchart.

Figure 2

Dysbiosis contribution to portal hypertension. The diagram illustrates the transition from eubiosis, characterized by a balanced gut microbiota, to dysbiosis, wherein microbial equilibriums are disrupted due to various pathological events. Under dysbiotic conditions, immune cell activation and the production of metabolites by both host and microbiome species lead to increased gut permeability, facilitating bacterial translocation into the portal veins. Consequently, this cascade of events triggers processes that diminish vascular resistance, enhance circulation dynamics, elevate intrahepatic vascular resistance, and ultimately result in increased matrix deposition in hepatic vessels, culminating in the onset of portal hypertension. This pathological state disrupts the normal gut–liver axis, exacerbating its self-propagating effects.