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

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Metab Target Organ Damage 2025;5:[Accepted].
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Abstract

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.

Keywords

TM6SF2, E167K, microbiome, gut liver axis, LPA pathway

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Kalligeros M, Henry L, Younossi ZM. Intestinal TM6SF2 and the gut–liver axis in MASLD: new insights. Metab Target Organ Damage 2025;5:[Accept]. http://dx.doi.org/10.20517/mtod.2025.37

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© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
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Metabolism and Target Organ Damage
ISSN 2769-6375 (Online)
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