Qiu Min, Ye Cong, Bao Lijuan, Wu Keyi, Zhao Yihong, Zhao Xiaotong, Tang Ruibo, Shang Ruping, Shang Shan, Yuan Chongshan, Hu Xiaoyu, Zhang Naisheng, Fu Yunhe, Wang Jun, Zhao Caijun
Department of Gynecology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China; Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province, China.
Department of Gynecology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China.
J Adv Res. 2024 Oct 5. doi: 10.1016/j.jare.2024.09.023.
In responses to antibiotics exposure, gut dysbiosis is a risk factor not only for pathogen infection but also for facilitating pathobiont expansion, resulting in increased inflammatory responses in the gut and distant organs. However, how this process is regulated has not been fully elucidated.
In this study, we investigated the role of sialic acid, a host-derived carbohydrate, in the pathogenesis of gut dysbiosis-derived inflammation in distant organs.
Ampicillin (Amp)-induced gut dysbiotic mice were treated with N-glycolylneuraminic acid (Neu5Gc) and N-acetylneuraminic acid (Neu5Ac) for three weeks to assess the role of sialic acids in mastitis. The underlying mechanism by which sialic acids regulate mastitis was explored using 16S rRNA sequencing, transcriptomics and employed multiple molecular approaches.
Administration of Neu5Ac and Neu5Gc exacerbated gut dysbiosis-induced mastitis and systemic inflammation. The gut dysbiosis caused by Amp was also aggravated by sialic acid. Notably, increased Enterococcus expansion, which was positively correlated with inflammatory markers, was observed in both Neu5Ac- and Neu5Gc-treated gut dysbiotic mice. Treatment of mice with Enterococcus cecorum (E. cecorum) aggravated gut dysbiosis-induced mastitis. Mechanically, sialic acid-facilitated E. cecorum expansion promoted muramyl dipeptide (MDP) release, which induced inflammatory responses by activating the NOD2-RIP2-NF-κB axis.
Collectively, our data reveal a role of sialic acid-facilitated postantibiotic pathobiont expansion in gut dysbiosis-associated inflammation, highlighting a potential strategy for disease prevention by regulating the MDP-NOD2-RIP2 axis.
在对抗生素暴露的反应中，肠道菌群失调不仅是病原体感染的危险因素，也是促进致病共生菌扩张的因素，导致肠道和远处器官的炎症反应增加。然而，这一过程是如何被调节的尚未完全阐明。
在本研究中，我们研究了宿主来源的碳水化合物唾液酸在远处器官肠道菌群失调所致炎症发病机制中的作用。
用N-羟乙酰神经氨酸（Neu5Gc）和N-乙酰神经氨酸（Neu5Ac）处理氨苄青霉素（Amp）诱导的肠道菌群失调小鼠三周，以评估唾液酸在乳腺炎中的作用。使用16S rRNA测序、转录组学并采用多种分子方法探索唾液酸调节乳腺炎的潜在机制。
给予Neu5Ac和Neu5Gc会加重肠道菌群失调诱导的乳腺炎和全身炎症。Amp引起的肠道菌群失调也因唾液酸而加剧。值得注意的是，在Neu5Ac和Neu5Gc处理的肠道菌群失调小鼠中均观察到肠球菌扩张增加，这与炎症标志物呈正相关。用盲肠肠球菌（E. cecorum）处理小鼠会加重肠道菌群失调诱导的乳腺炎。从机制上讲，唾液酸促进的肠球菌扩张促进了胞壁酰二肽（MDP）的释放，MDP通过激活NOD2-RIP2-NF-κB轴诱导炎症反应。
总体而言，我们的数据揭示了唾液酸促进抗生素后致病共生菌在肠道菌群失调相关炎症中的扩张作用，突出了通过调节MDP-NOD2-RIP2轴预防疾病的潜在策略。
