Letter to the Editor: Circadian and microbial misalignment in metabolic dysfunction-associated steatotic liver disease - mechanistic insights and chronotherapeutic potential

Abstract

We read with interest the article by Rusman et al published in World Journal of Experimental Medicine. Beyond microbial composition, the gut–liver axis is a rhythmic system regulated by a bidirectional interaction between host clocks and the gut microbiota. Social jetlag induces “temporal dysbiosis”, disrupting the timing of metabolites and compromising the intestinal barrier, which exacerbates metabolic injury in metabolic dysfunction-associated steatotic liver disease. Restoration of these rhythms through chronotherapeutic approaches provides an effective method to restore alignment and improve clinical outcomes. Specifically, social jetlag desynchronizes hepatic clocks and disrupts microbially-modified bile acid signaling, promoting fat accumulation. Chronotherapeutic strategies like time-restricted eating can effectively mitigate disease progression by “reprogramming” the liver transcriptome and reducing hepatic triglycerides.

Keywords: Circadian disruption; Steatotic liver disease; Time-restricted eating; Melatonin; Chronotherapy

Core Tip: The gut-liver axis is a rhythmic system regulated by a bidirectional interaction between host clocks and the gut microbiota. Social jetlag disrupts the timing of metabolites and compromises the intestinal barrier, exacerbating metabolic injury in metabolic dysfunction-associated steatotic liver disease. Restoration of these rhythms through chronotherapeutic approaches provides an effective method to restore alignment and improve clinical outcomes.