Gut microbiota-derived GlcNAc-MurNAc is a TLR4 agonist that protects the host gut.

IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Chenyu Li, Christopher Adamson, Allan Wee Ren Ng, Yaquan Liang, Zebin Hong, Jia Tong Loh, Siu-Kin Ng, Jeric Mun Chung Kwan, Shiliu Feng, Evan Wei Long Ng, Sajith Nair, Christiane Ruedl, Sunny Hei Wong, Kong-Peng Lam, Yuan Qiao
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引用次数: 0

Abstract

Gut microbiota-derived peptidoglycan fragments (PGNs) are key signaling molecules that regulate multiple aspects of the host's health. Yet the exact structures of natural PGNs in hosts have not been fully elucidated. Herein, we developed an LC-HRMS/MS analytical platform for global quantification and profiling of natural PGN subtypes in host gut and sera, unexpectedly revealing the abundance of PGN-derived saccharide moieties that do not resemble canonical ligands of mammalian NOD1/2 receptors. Focusing on the disaccharide GlcNAc-MurNAc (GM), which does not activate NOD1/2 yet still exhibits immunostimulatory effects in host immune cells, we established GM as a mild TLR4 agonist, illustrating an alternate PGN sensing mechanism other than NOD signaling. Importantly, the administration of GM mitigates colonic inflammation in the DSS-induced colitis model in mice via a TLR4-dependent manner, highlighting the in vivo significance of gut microbiota-derived PGN saccharides in maintaining host intestinal homeostasis.

肠道微生物源性GlcNAc-MurNAc是一种保护宿主肠道的TLR4激动剂。
肠道微生物衍生的肽聚糖片段(PGNs)是调节宿主健康多个方面的关键信号分子。然而,宿主体内天然PGNs的确切结构尚未完全阐明。在此,我们开发了一个LC-HRMS/MS分析平台,用于宿主肠道和血清中天然PGN亚型的全球定量和分析,意外地揭示了与哺乳动物NOD1/2受体的典型配体不同的PGN衍生糖基的丰度。我们关注的是双糖GlcNAc-MurNAc (GM),它不会激活NOD1/2,但在宿主免疫细胞中仍表现出免疫刺激作用,我们建立了GM作为一种温和的TLR4激动剂,说明了NOD信号之外的另一种PGN感知机制。重要的是,转基因通过tlr4依赖的方式减轻了dss诱导的小鼠结肠炎模型中的结肠炎症,突出了肠道微生物源性PGN糖在维持宿主肠道稳态中的体内意义。
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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
期刊介绍: Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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