关键词: Gut microbiota dysbiosis TLR2 activation capsular polysaccharide nontuberculous mycobacterial lung disease prevotella copri

Mesh : Dysbiosis / microbiology Gastrointestinal Microbiome Animals Toll-Like Receptor 2 / metabolism genetics Humans Mice Male Female Mycobacterium Infections, Nontuberculous / microbiology Middle Aged Feces / microbiology Aged Prevotella Lung Diseases / microbiology Nontuberculous Mycobacteria Disease Susceptibility Mice, Inbred C57BL Lung / microbiology

来  源:   DOI:10.1080/19490976.2024.2361490   PDF(Pubmed)

Abstract:
The role of gut microbiota in host defense against nontuberculous mycobacterial lung disease (NTM-LD) was poorly understood. Here, we showed significant gut microbiota dysbiosis in patients with NTM-LD. Reduced abundance of Prevotella copri was significantly associated with NTM-LD and its disease severity. Compromised TLR2 activation activity in feces and plasma in the NTM-LD patients was highlighted. In the antibiotics-treated mice as a study model, gut microbiota dysbiosis with reduction of TLR2 activation activity in feces, sera, and lung tissue occurred. Transcriptomic analysis demonstrated immunocompromised in lung which were closely associated with increased NTM-LD susceptibility. Oral administration of P. copri or its capsular polysaccharides enhanced TLR2 signaling, restored immune response, and ameliorated NTM-LD susceptibility. Our data highlighted the association of gut microbiota dysbiosis, systematically compromised immunity and NTM-LD development. TLR2 activation by P. copri or its capsular polysaccharides might help prevent NTM-LD.
摘要:
肠道菌群在宿主防御非结核性分枝杆菌肺病(NTM-LD)中的作用知之甚少。这里,我们在NTM-LD患者中显示出明显的肠道菌群失调。Prevotellacopri的丰度降低与NTM-LD及其疾病严重程度显着相关。强调了NTM-LD患者粪便和血浆中受损的TLR2活化活性。在抗生素治疗的小鼠作为研究模型,肠道菌群失调与粪便中TLR2活化活性降低,sera,和肺组织发生。转录组分析显示肺部免疫受损,与NTM-LD易感性增加密切相关。口服P.copri或其荚膜多糖可增强TLR2信号传导,恢复免疫反应,改善了NTM-LD敏感性。我们的数据强调了肠道微生物群失调的关联,系统性受损的免疫力和NTM-LD的发展。通过P.copri或其荚膜多糖激活TLR2可能有助于预防NTM-LD。
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