Exploring the Relationship between Liver Disease, Bacterial Translocation, and Dysbiosis: Unveiling the Gut-Liver Axis

Abstract

Background: The global burden of liver disease and cirrhosis has been progressively increasing in the last decade. The interplay between gut microbiota and immune system and the bidirectional relationship with the liver, known as the gut-liver axis, has arisen as a fundamental aspect of liver disease.

Summary: Alterations of the gut microbiome have been described and include both dysbiotic microbial signatures and intestinal bacterial overgrowth. The integrity of the intestinal epithelial barrier is essential for preventing the access of harmful substances and bacterial products into the host. Bacterial translocation due to altered host-microbiota interactions triggers local immune cell activation and facilitates a chronic inflammatory state that can ultimately lead to immune exhaustion, characteristic of cirrhosis. In cirrhosis, breakdown of the gut vascular barrier allows access of bacterial products to portal blood circulation and facilitates their influx into the liver, further contributing to disease progression.

Key messages: A better understanding of the contributing factors to pathological bacterial translocation and the impact of dysbiosis in liver disease will lead to achieve innovative therapeutic strategies in cirrhosis.

Keywords: Bacterial translocation; Cirrhosis; Dysbiosis; Gut-liver axis; Liver disease.

Fig. 1.

Medical interventions focused on restoring a balanced equilibrium in the gut-liver axis. Therapeutic strategies targeting the gut-liver axis include administration of probiotics, prebiotics, and diet interventions (a); fecal microbiota transplants from donors with healthy microbiota to patients with liver disease (b); antibiotic therapy or prophylaxis (c); bile acid modulation (d); enterosorbent CARBALIVE™ (e); and dialysis device DIALIVE (f). AMPs, antimicrobial peptides; DC, dendritic cell; FXR, farnesoid X receptor; G, goblet cell; GVB, gut vascular barrier; HSC, hepatic stellate cell; IFN, interferon; IL, interleukin; KC, Kupffer cell; M, macrophage; MUC2, mucin 2; N, neutrophil; NO, nitric oxide; OCA, obeticholic acid; PAMPs, pathogen-associated molecular patterns; PC, Paneth cell; PV1, plasmalemmal vesicle-associated protein-1; ROS, reactive oxygen species; SCFA, short-chain fatty acid; T, T cell; TJ/AJ, tight junction/adherens junction; TNF, tumor necrosis factor.