In HFD-induced MAFLD mouse models with disrupted gut microbiota, levels of the pro-inflammatory cytokine high mobility group box 1 (HMGB1) are significantly elevated in the intestinal tissue, enabling its transfer via mEVs from the compromised intestinal barrier to the liver, where it activates Toll-like Receptor 4 (TLR4), ultimately resulting in hepatic inflammation and liver dysfunction (164, 165). Here, TLR4 is linked to inflammation.