Immunology of gut microbiome and liver in non-alcoholic fatty liver disease (NAFLD): mechanisms, bacteria, and novel therapeutic targets

Abstract

Non-alcoholic fatty liver disease (NAFLD) is linked to lifestyle factors such as diet and obesity. The gut microbiome’s influence on immune pathways and dysregulations is increasingly recognized in NAFLD. The gut microbiome can significantly modulate immune and inflammatory responses in NAFLD and other liver diseases. We explore how the microbiome impacts local and systemic immune responses contributing to NAFLD’s development, discussing mechanisms and novel interventions like probiotics. Our review points out different immune system pathways and microorganisms regulating metabolism, liver inflammation and fibrosis. We specifically mention TLR-4 as a key immune pathway activated by bacterial lipopolysaccharides producing pro-inflammatory cytokines. Also, we mention endotoxin-producing strains (Enterobacter cloacae B29, Escherichia coli PY102, Klebsiella pneumoniae A7) that can induce NAFLD in animal models by activating TLR4-dependent immune response. These bacteria may also contribute to NAFLD pathogenesis via other immune and non-immune mechanisms. In the end we discuss future perspective of gut microbiome research in NAFLD as a potential new target for both diagnostic and treatment.