Gut dysbiosis induces the development of mastitis through a reduction in host anti-inflammatory enzyme activity by endotoxemia.
Gut dysbiosis induces the development of mastitis through a reduction in host anti-inflammatory enzyme activity by endotoxemia.
复制标题
DOI：
10.1186/s40168-022-01402-z
复制
发表时间：
2022-12-01
期刊：
影响因子：
15.5
通讯作者：
中科院分区：
文献类型：
--
作者：
越来越多的实验证据表明，肠道菌群在乳腺炎的发病中起着重要作用，临床研究发现，乳腺炎的发生与瘤胃微生态失调有关。然而，瘤胃微生物群参与乳腺炎发展的潜在机制仍然未知。在本研究中，我们发现，临床型乳房炎奶牛有明显的全身炎症，这是与显着的瘤胃生态失调，特别是丰富的变形菌在瘤胃。从乳腺炎奶牛（M-RMT）向小鼠移植瘤内微生物群会在受体小鼠中诱导乳腺炎症状，沿着TLR 4-cGAS-STING-NF-κB/NLRP 3途径的乳腺促炎特征激活增加。M-RMT还诱导粘膜炎症和肠屏障完整性受损，导致内毒素血症和全身炎症增加。此外，我们表明，M-RMT反映了受体小鼠肠道中的瘤胃微生物群破坏，如丰富的变形菌门和类似的细菌功能所证明的，这与小鼠中的大多数促炎参数和血清脂多糖（LPS）水平相关。反复低级别LPS治疗反映了肠道生态失调诱导的内毒素血症，并导致小鼠严重乳腺炎。此外，我们发现肠道生态失调衍生的LPS通过激活神经氨酸酶（Neu）降低宿主碱性磷酸酶活性，这有助于低水平LPS暴露和E。大肠杆菌诱导的小鼠乳腺炎。相反，用小牛肠碱性磷酸酶或Neu抑制剂扎那米韦治疗减轻了低级别LPS暴露和E。大肠杆菌诱导的小鼠乳腺炎。我们的研究结果表明，瘤胃微生态失调引起的低度内毒素血症可通过损害宿主抗炎酶引起乳腺炎并加重病原体诱导的乳腺炎，这意味着调节瘤胃或肠道微生物群以防止低度全身性炎症是乳腺炎干预的潜在策略。视频摘要在线版本包含补充材料，可通过10. 1186/s40168-022-01402-z获取。
Mounting experimental evidence has shown that the gut microbiota plays a significant role in the pathogenesis of mastitis, and clinical investigations have found that the occurrence of mastitis is correlated with ruminal dysbiosis. However, the underlying mechanism by which the ruminal microbiota participates in the development of mastitis remains unknown. In the present study, we found that cows with clinical mastitis had marked systemic inflammation, which was associated with significant ruminal dysbiosis, especially enriched Proteobacteria in the rumen. Ruminal microbiota transplantation from mastitis cows (M-RMT) to mice induced mastitis symptoms in recipient mice along with increased mammary proinflammatory signature activation of the TLR4-cGAS-STING-NF-κB/NLRP3 pathways. M-RMT also induced mucosal inflammation and impaired intestinal barrier integrity, leading to increased endotoxemia and systemic inflammation. Moreover, we showed that M-RMT mirrored ruminal microbiota disruption in the gut of recipient mice, as evidenced by enriched Proteobacteria and similar bacterial functions, which were correlated with most proinflammatory parameters and serum lipopolysaccharide (LPS) levels in mice. Recurrent low-grade LPS treatment mirrored gut dysbiosis-induced endotoxemia and caused severe mastitis in mice. Furthermore, we found that gut dysbiosis-derived LPS reduced host alkaline phosphatase activity by activating neuraminidase (Neu), which facilitates low-grade LPS exposure and E. coli-induced mastitis in mice. Conversely, treatment with calf intestinal alkaline phosphatase or the Neu inhibitor zanamivir alleviated low-grade LPS exposure and E. coli-induced mastitis in mice. Our results suggest that ruminal dysbiosis-derived low-grade endotoxemia can cause mastitis and aggravate pathogen-induced mastitis by impairing host anti-inflammatory enzymes, which implies that regulating the ruminal or gut microbiota to prevent low-grade systemic inflammation is a potential strategy for mastitis intervention. Video Abstract The online version contains supplementary material available at 10.1186/s40168-022-01402-z.
登录
查看更多内容
影响因子：
4.1
作者：
FOLLEY, SJ;GREENBAUM, AL
通讯作者：
GREENBAUM, AL
影响因子：
3.5
作者：
Kusebauch, Ulrike;Hernandez-Castellano, Lorenzo E.;Bendixen, Emoke
通讯作者：
Bendixen, Emoke
DOI：
10.1073/pnas.1719834115
发表时间：
2018-01-30
影响因子：
11.1
作者：
Gorelik, Alexei;Illes, Katalin;Nagar, Bhushan
通讯作者：
Nagar, Bhushan
DOI：
10.1038/s41577-021-00524-z
发表时间：
2021-09
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Decout A;Katz JD;Venkatraman S;Ablasser A
通讯作者：
Ablasser A
DOI：
10.3390/ani11113108
发表时间：
2021-10-30
期刊：
Animals : an open access journal from MDPI
影响因子：
--
作者：
Chuang ST;Li KY;Tu PW;Ho ST;Hsu CC;Hsieh JC;Chen MJ
通讯作者：
Chen MJ