Phytosphingosine contributes gut microbiota metabolism to alleviate low-grade endotoxemia-induced mastitis

作者：Yihong Zhao, Hongyan Li, Jiawen Xu, Haiqi Li, Lijuan Bao, Keyi Wu, Min Qiu, Hang Yu, Shang Shan, Yuhong He, Chongshan Yuan, Naisheng Zhang, Xiaoyu Hu, Yunhe Fu, Wenjia Li, Caijun Zhao, Jun Wang · 发表于：Microbiome · 年份：2025 · DOI：10.1186/s40168-025-02266-9 · 被引用次数：1 · 研究领域：Gut microbiota and health、Milk Quality and Mastitis in Dairy Cows、Phytoestrogen effects and research

BACKGROUND: Recently, evidence has indicated that mastitis is closely associated with the ruminal dysbiosis caused by subacute ruminal acidosis (SARA) and subsequent low-grade endotoxemia (LGE). However, whether and how ruminal metabolic dysbiosis influences SARA-associated mastitis is still unclear. RESULTS: Using untargeted metabolomics, we found that cows with SARA-associated mastitis exhibited altered ruminal metabolic profiles, particularly a reduced level of phytosphingosine (PS), compared to healthy cows. Oral administration of PS to mice alleviated LGE-induced mastitis, as evidenced by attenuated mammary injury and improved function of mammary tight junctions (TJs). Furthermore, we demonstrated that LGE induced significant gut dysbiosis, characterized by increased abundances of opportunistic pathogens such as Enterococcus, which was mitigated by PS treatment. Interestingly, transplantation of both fecal microbiota (FMT) and matched sterile supernatant (FST) from PS-treated mice alleviated LGE-induced mastitis, restored the blood-milk barrier, and modulated the gut microbiota in recipient mice following LGE exposure. Additionally, PS and PS-FMT treatments increased the abundances of fecal short-chain fatty acid (SCFA) producers, accompanied by elevated fecal SCFA levels, particularly butyric acid, in PS- and PS-FMT-treated mice. Butyric acid was negatively correlated with mammary inflammatory markers, and butyrate administration attenuated LGE-induced mastitis in mice....