Intestinal TM6SF2 and the gut–liver axis in MASLD: new insights

Metabolic dysfunction–associated steatotic liver disease (MASLD) and metabolic dysfunction–associated steatohepatitis (MASH) involve a complex interplay of genetics, metabolism, and the gut–liver axis. In a new study, Zhang et al. assess a previously unrecognized role of the intestinal epithelium in protecting against MASH by focusing on Transmembrane 6 Superfamily Member 2 (TM6SF2), a gene highly expressed in both liver and intestine, whose common loss-of-function variant (E167K) is a well-established genetic risk factor for MASLD/MASH in humans. Herein, we provide an overview of Zhang et al.’s study and highlight the clinical significance of these new findings by focusing on two specific areas: the gut–liver axis in MASLD and the modification of the intestinal microbiota.