Gut Microbiota and NAFLD: Pathogenetic Mechanisms, Microbiota Signatures, and Therapeutic Interventions

Tomas Hrncir, Lucia Hrncirova, Miloslav Kverka, Robert Hromadka, Vladimira Machova, Eva Trckova, Klara Kostovcikova, Pavlina Kralickova, Jan Krejsek, Helena Tlaskalova-Hogenova, Tomas Hrncir, Lucia Hrncirova, Miloslav Kverka, Robert Hromadka, Vladimira Machova, Eva Trckova, Klara Kostovcikova, Pavlina Kralickova, Jan Krejsek, Helena Tlaskalova-Hogenova

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Its worldwide prevalence is rapidly increasing and is currently estimated at 24%. NAFLD is highly associated with many features of the metabolic syndrome, including obesity, insulin resistance, hyperlipidaemia, and hypertension. The pathogenesis of NAFLD is complex and not fully understood, but there is increasing evidence that the gut microbiota is strongly implicated in the development of NAFLD. In this review, we discuss the major factors that induce dysbiosis of the gut microbiota and disrupt intestinal permeability, as well as possible mechanisms leading to the development of NAFLD. We also discuss the most consistent NAFLD-associated gut microbiota signatures and immunological mechanisms involved in maintaining the gut barrier and liver tolerance to gut-derived factors. Gut-derived factors, including microbial, dietary, and host-derived factors involved in NAFLD pathogenesis, are discussed in detail. Finally, we review currently available diagnostic and prognostic methods, summarise latest knowledge on promising microbiota-based biomarkers, and discuss therapeutic strategies to manipulate the microbiota, including faecal microbiota transplantation, probiotics and prebiotics, deletions of individual strains with bacteriophages, and blocking the production of harmful metabolites.

Keywords: cirrhosis; faecal microbiota transplantation; gut microbiota dysbiosis; hepatocellular carcinoma; intestinal permeability; liver steatosis; loss of diversity.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The gut–liver axis and the role of the gut microbiome in the pathogenesis of NAFLD. The gut microbiome altered by environmental factors induces hepatic steatosis. The dysfunctional liver fails to restore gut eubiosis, which results in a vicious self-perpetuating loop, promoting NAFLD progression. The communication via systemic mediators is not shown. NAFLD, non-alcoholic fatty liver disease; MAMP, microbe-associated molecular pattern; LPS, lipopolysaccharide; TMA, trimethylamine; SCFA, short-chain fatty acid; DCA, deoxycholic acid; CDCA, chenodeoxycholic acid.

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