Lactobacillus amylovorus extracellular vesicles mitigate mammary gland ferroptosis via the gut-mammary gland axis.

Lactation is essential for supporting neonatal growth and development, and its regulation is influenced by the gut microbiota. However, the role of gut microbes in lactation under conditions of oxidative stress remains unclear. In this study, we identify a novel function for gut microbiota in regulating maternal lactation through the modulation of ferroptosis in the mammary gland under oxidative stress. We identify Lactobacillus amylovorus (L. amylovorus), enriched in mothers with low oxidative stress, as negatively correlating with both oxidative stress and ferroptosis. In a mouse model, L. amylovorus alleviates mammary ferroptosis and promotes lactation. In addition to producing of short-chain fatty acids, L. amylovorus secretes bacterial extracellular vesicles (BEVs) enriched in oleic acid, a monounsaturated fatty acid that can be transferred to the mammary gland. Mechanistically, the accumulation of oleic acid in mammary epithelial cells enhances their resistance to ferroptosis, thereby supporting milk production. These findings highlight the potential of L. amylovorus and its BEVs as therapeutic tools to counteract oxidative stress-induced lactation decline.