Elevated muramyl dipeptide by sialic acid-facilitated postantibiotic pathobiont expansion contributes to gut dysbiosis-induced mastitis in mice,Journal of Advanced Research

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Elevated muramyl dipeptide by sialic acid-facilitated postantibiotic pathobiont expansion contributes to gut dysbiosis-induced mastitis in mice
Journal of Advanced Research ( IF 11.4 ) Pub Date : 2024-10-05 , DOI: 10.1016/j.jare.2024.09.023
Min Qiu, Cong Ye, Lijuan Bao, Keyi Wu, Yihong Zhao, Xiaotong Zhao, Ruibo Tang, Ruping Shang, Shan Shang, Chongshan Yuan, Xiaoyu Hu, Naisheng Zhang, Yunhe Fu, Jun Wang, Caijun Zhao

Introduction

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.

Objectives

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.

Methods

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.

Results

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.

Conclusions

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.

更新日期：2024-10-06

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