Bacteroides and NAFLD: pathophysiology and therapy

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition observed globally, with the potential to progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. Currently, the US Food and Drug Administration (FDA) has not approved any drugs for the treatment of NAFLD. NAFLD is characterized by histopathological abnormalities in the liver, such as lipid accumulation, steatosis, hepatic balloon degeneration, and inflammation. Dysbiosis of the gut microbiota and its metabolites significantly contribute to the initiation and advancement of NAFLD. Bacteroides, a potential probiotic, has shown strong potential in preventing the onset and progression of NAFLD. However, the precise mechanism by which Bacteroides treats NAFLD remains uncertain. In this review, we explore the current understanding of the role of Bacteroides and its metabolites in the treatment of NAFLD, focusing on their ability to reduce liver inflammation, mitigate hepatic steatosis, and enhance intestinal barrier function. Additionally, we summarize how Bacteroides alleviates pathological changes by restoring the metabolism, improving insulin resistance, regulating cytokines, and promoting tight-junctions. A deeper comprehension of the mechanisms through which Bacteroides is involved in the pathogenesis of NAFLD should aid the development of innovative drugs targeting NAFLD.

Keywords: Bacteroides; NAFLD; intestinal barrier; liver inflammation; steatosis.

FIGURE 1

Potential mechanisms underlying the attenuation of hepatic steatosis by Bacteroides in NAFLD. Bacteroides and its active ingredient, bacterial extracellular vesicles (BEVs), alleviate hepatic steatosis and associated insulin resistance. AMPK, adenosine monophosphate-activated protein kinase; mTOR, mechanistic target of rapamycin; SREBP-1, sterol regulatory element-binding protein-1; ChREBP, carbohydrate response element-binding protein; ACC, acetyl-CoA carboxylase; FAS, fatty acid synthase; BEVs, bacterial extracellular vesicles; BSH, bile salt hydrolase; TGR5, takeda G protein-coupled receptor 5; FXR, farnesoid X receptor; DPP-4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide-1; IR, insulin resistance; PPARα, peroxisome proliferator-activated receptor α.

FIGURE 2

Potential mechanisms contributing to the prevention of hepatic inflammation by Bacteroides in NAFLD. Bacteroides regulated inflammation and immune response in the livers of NAFLD patients. The current focus on the mechanisms underlying the improvement of hepatic inflammation by Bacteroides primarily revolves around the production of inflammatory factors and LPS and TLR4 signaling. IL-22, interleukin-22; IFN-γ, interferon-γ; IL-10, interleukin-10; LPS, lipopolysaccharide; TNF-α, tumor necrosis factor-α; PSA, polysaccharide A; TLR4, toll-like receptor 4; NF-κB, nuclear factor-κB; IL-1β, interleukin-1β.

FIGURE 3

Potential mechanisms involved in enhancing the intestinal barrier function by Bacteroides in NAFLD. Bacteroides and its metabolites enhance the barrier function of the intestine through modulating intestinal inflammatory factors, improving the expression of tight-junction proteins, and restoring intestinal dysbiosis. DC, dendritic cells; F. prausnitzii, Faecalibacterium prausnitzii; IL-10, interleukin-10; ZO-1, zonula occludens-1; PSA, polysaccharide A; IL-17, interleukin 17; TJ, tight-junction.