Histone lactylation scarring transmits metabolic and epigenetic memory across the gut-liver axis.

Histone H3K9 lactylation in colonic macrophages persists after colitis resolution and promotes susceptibility to metabolic liver disease under high-fat diet in mice.

• Why it matters: Understanding how prior intestinal inflammation influences delayed liver injury is crucial for preventing MASLD in patients with ulcerative colitis, as current mechanisms remain unclear.
• What they did: The study used mouse models of colitis and high-fat diet challenge, revealing that colonic macrophages retain H3K9la and heightened glycolysis, then traffic to the liver to promote steatosis, with key roles for BRG1 and CEBPB in maintaining this memory.
• The result: Disrupting macrophage trafficking or deleting Smarca4 reduces macrophage memory and protects against MASLD, suggesting targeting epigenetic and cellular memory pathways could prevent metabolic liver disease post-colitis.