Visiting MASLD through the lens of sex, immunity, and microbial interactions

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multifactorial disorder with immunometabolic imprints that differ significantly by sex. Although sex differences in disease susceptibility and progression have been recognized in other systems, they remain understudied in MASLD. Here, we explore how sex-based immune responses, metabolic stressors (diet, drugs, and lifestyle), and the gut microbiome contribute to disease variability. Wherever applicable, we take into account sex as a biological variable. We also analyzed phylum-level microbiome data from Human Gut Microbiome Atlas using an interpretable machine learning framework to predict and explain the classification features associated with MASLD. Our integrative approach underscores the need for sex-specific diagnostics and interventions incorporating host–microbiome–immune interactions.