Atg2 coordinates microbial metabolite signaling and epigenetic remodeling to maintain intestinal lipid homeostasis in Drosophila (microbiomejournal.biomedcentral.com)

• Atg2 loss in Drosophila intestinal progenitors causes dysbiosis and SCFA overproduction.
• SCFAs drive acetyl-CoA-dependent hyperacetylation, activating lipogenesis and innate immunity.
• Histidine supplementation and HDAC3 overexpression rescue lipid accumulation and immune activation.

"This study demonstrates that the autophagy-related protein Atg2 in Drosophila intestinal stem cells integrates microbiota-derived signals to maintain lipid and immune homeostasis. Atg2 deficiency causes dysbiosis, overproduction of short-chain fatty acids (SCFAs), and acetyl-CoA overflow, leading to global protein hyperacetylation that activates lipogenic and innate immune programs. Microbiota ablation or SCFA restriction fully reverses these pathologies. Histidine supplementation rescues lipid accumulation and extends lifespan. HDAC3 overexpression normalizes the phenotypes, highlighting an autophagy–microbiota–epigenetic axis."