Department of Gynecology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, China.
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, 130062, China.
J Nanobiotechnology. 2024 Nov 15;22(1):712. doi: 10.1186/s12951-024-02997-1.
A high grain diet causes an ecological imbalance in the gut microbiota and serves as an important endogenous trigger of mastitis in dairy cows, but the underlying mechanisms are unclear. Our previous study revealed that subacute rumen acidosis (SARA)-associated mastitis has distinct metabolic profiles in the rumen, especially a significant increase in succinate, but the role of succinate in the pathogenesis of mastitis remains unclear.
Succinate treatment exacerbates low-grade endotoxemia-induced mastitis in mice. Specifically, succinate increased the production of gut microbiota-extracellular vehicles (mEVs) containing lipopolysaccharides, which can diffuse across the damaged intestinal barrier into the mammary glands. Administration of mEVs promotes mammary inflammation via activation of the TLR4/NF-κB pathway.
Our findings suggest that succinate promotes mastitis through the proliferation of enteric pathogens and mEVs production, suggesting a potential strategy for mastitis intervention on the basis of intestinal metabolic regulation and pathogen inhibition. The role of mEVs in interspecific communication has also been elucidated.
高谷物饮食会导致肠道微生物群落失衡，成为奶牛乳腺炎的一个重要内源性触发因素，但具体机制尚不清楚。我们之前的研究表明，与亚急性瘤胃酸中毒（SARA）相关的乳腺炎在瘤胃中有明显不同的代谢特征，特别是琥珀酸显著增加，但琥珀酸在乳腺炎发病机制中的作用尚不清楚。
琥珀酸盐处理可加重低水平内毒素血症诱导的小鼠乳腺炎。具体而言，琥珀酸增加了含有脂多糖的肠道微生物群外囊泡（mEVs）的产生，这些囊泡可以穿过受损的肠道屏障扩散到乳腺。mEVs 通过激活 TLR4/NF-κB 通路促进乳腺炎症。
我们的研究结果表明，琥珀酸通过促进肠道病原体增殖和 mEVs 的产生来促进乳腺炎，这为基于肠道代谢调节和病原体抑制的乳腺炎干预提供了一种潜在策略。mEVs 在种间通讯中的作用也得到了阐明。
