He Zhaoqi, Zhao Caijun, He Yuhong, Liu Zhuoyu, Fan Guyue, Zhu Kun, Wang Yiqi, Zhang Naisheng, Fu Yunhe, Hu Xiaoyu
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, 130062, Jilin Province, China.
J Anim Sci Biotechnol. 2023 Dec 20;14(1):157. doi: 10.1186/s40104-023-00952-y.
Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety. Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in 'gastroenterogenic mastitis'. However, the mechanism has not been fully clarified. Recently, we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows, and the abundance of Stenotrophomonas maltophilia (S. maltophilia) was significantly increased in both the rumen and milk microbiota. Accordingly, we hypothesized that 'gastroenterogenic mastitis' can be induced by the migration of endogenous gut bacteria to the mammary gland. Therefore, this study investigated the mechanism by which enterogenic S. maltophilia induces mastitis.
First, S. maltophilia was labelled with superfolder GFP and administered to mice via gavage. The results showed that treatment with S. maltophilia promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier, leading to intestinal inflammation and intestinal leakage. Furthermore, tracking of ingested S. maltophilia revealed that S. maltophilia could migrate from the gut to the mammary gland and induce mastitis. Subsequently, mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with S. maltophilia. Then, using mouse mammary epithelial cells (MMECs), we verified that S. maltophilia induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy pathway.
In conclusion, the results showed that enterogenic S. maltophilia could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce mastitis. Targeting the gut-mammary gland axis may also be an effective method to treat mastitis.
乳腺炎是一种乳腺炎症性疾病，对乳制品行业有严重的经济影响，并危及食品安全。我们之前的研究发现，机体存在肠道/瘤胃-乳腺轴，肠道/瘤胃微生物群的紊乱可导致“胃肠源性乳腺炎”。然而，其机制尚未完全阐明。最近，我们发现长期饲喂高浓缩日粮可诱发奶牛乳腺炎，瘤胃和乳微生物群中嗜麦芽窄食单胞菌（S. maltophilia）的丰度均显著增加。因此，我们推测“胃肠源性乳腺炎”可由内源性肠道细菌迁移至乳腺诱发。因此，本研究探讨了肠源性嗜麦芽窄食单胞菌诱发乳腺炎的机制。
首先，用超级折叠绿色荧光蛋白标记嗜麦芽窄食单胞菌，并通过灌胃给予小鼠。结果表明，嗜麦芽窄食单胞菌处理促进了乳腺炎的发生，并增加了血乳屏障的通透性，导致肠道炎症和肠漏。此外，对摄入的嗜麦芽窄食单胞菌进行追踪发现，嗜麦芽窄食单胞菌可从肠道迁移至乳腺并诱发乳腺炎。随后，乳腺转录组分析表明，在嗜麦芽窄食单胞菌处理的小鼠中，钙和AMPK信号通路显著上调。然后，我们使用小鼠乳腺上皮细胞（MMECs）证实，嗜麦芽窄食单胞菌通过激活钙-ROS-AMPK-mTOR-自噬途径诱发乳腺炎。
总之，结果表明肠源性嗜麦芽窄食单胞菌可通过肠-乳腺轴从肠道迁移至乳腺，并激活钙-ROS-AMPK-mTOR-自噬途径诱发乳腺炎。靶向肠-乳腺轴也可能是治疗乳腺炎的有效方法。
