A Calorie-restricted Dietary Intervention Alleviates Obesity-induced MASLD via the Microbiota-5-hydroxyindoleacetic acid–Pregnane X Receptor Axis

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the most common chronic liver disease worldwide. Caloric restriction (CR) is a major dietary intervention known to reshape the gut microbiota; however, the implications of these microbial changes for MASLD pathophysiology are not yet fully elucidated. We propose a new caloric restriction intervention which ameliorates MASLD by shaping the gut microbiome that elevates 5-HIAA levels, thereby activating the hepatic PXR receptor.