Fig. 4

Putative mechanisms for a role of microbiota-mediated ASNP effect on MAFLD. The adsorption of exogenous and endogenous bioactive molecules to ASNP may change the microbial gut signature leading to dysbiosis and rewiring of microbiota metabolism [e.g. reduction of butyrate). The alteration of homeostasis may impair epithelial barrier function causing increased portal blood levels of endotoxin and other PAMPS. Resident liver Kupffer and stellate cells, activated through TLR4-dependent signaling, secrete both pro-inflammatory and fibrogenic cytokines. The establishment of a chronic inflammatory condition may account for the alteration of glucose metabolism in hepatocytes (insulin resistance) and the accumulation of lipids (metabolic-associated fatty liver (MAFL)] and favors the evolution toward metabolic-associated steatohepatitis (MASH)