精氨酸重塑肠道菌群,改善对非结核分枝杆菌的肺部免疫防御
  • 代谢组学分析显示,非结核分枝杆菌(NTM)肺病患者和NTM感染小鼠血清中L-精氨酸降低;
  • 口服L-精氨酸可显著增强NTM感染小鼠的肺部抗菌活性,增加肺内的产IFN-γ效应T细胞和M1巨噬细胞的数量;
  • 移植经L-精氨酸治疗小鼠的粪便菌群,可增强小鼠对NTM肺病的抵抗力,而抗生素会削弱L-精氨酸的保护作用;
  • 菌群分析表明,L-精氨酸促进假长双歧杆菌富集,口服假长双歧杆菌或其代谢物肌苷,可增强小鼠对NTM(包括耐药株)感染的肺部免疫防御。
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肠-肺轴的发现为治疗肺部疾病打开了新思路,Gut Microbes发表的这项研究探索了对非结核分枝杆菌肺病有免疫保护作用的肠菌和代谢物。
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Gut Microbes [IF:9.434]

Arginine-mediated gut microbiome remodeling promotes host pulmonary immune defense against nontuberculous mycobacterial infection

精氨酸介导的肠道菌群重塑促进宿主对非结核分枝杆菌感染的肺部免疫防御

10.1080/19490976.2022.2073132

05-17, Article

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Nontuberculous mycobacterial pulmonary diseases (NTM-PDs) are emerging as global health threats with issues of antibiotic resistance. Accumulating evidence suggests that the gut–lung axis may provide novel candidates for host-directed therapeutics against various infectious diseases. However, little is known about the gut–lung axis in the context of host protective immunity to identify new therapeutics for NTM-PDs. This study was performed to identify gut microbes and metabolites capable of conferring pulmonary immunity to NTM-PDs. Using metabolomics analysis of sera from NTM-PD patients and mouse models, we showed that the levels of l-arginine were decreased in sera from NTM-PD patients and NTM-infected mice. Oral administration of l-arginine significantly enhanced pulmonary antimicrobial activities with the expansion of IFN-γ-producing effector T cells and a shift to microbicidal (M1) macrophages in the lungs of NTM-PD model mice. Mice that received fecal microbiota transplants from l-arginine-treated mice showed increased protective host defense in the lungs against NTM-PD, whereas l-arginine-induced pulmonary host defense was attenuated in mice treated with antibiotics. Using 16S rRNA sequencing, we further showed that l-arginine administration resulted in enrichment of the gut microbiota composition with Bifidobacterium species. Notably, oral treatment with either Bifidobacterium pseudolongum or inosine enhanced antimicrobial pulmonary immune defense against NTM infection, even with multidrug-resistant clinical NTM strains. Our findings indicate that l-arginine-induced gut microbiota remodeling with enrichment of B. pseudolongum boosts pulmonary immune defense against NTM infection by driving the protective gut–lung axis in vivo.

First Authors:
Young Jae Kim,June-Young Lee,Jae Jin Lee,Sang Min Jeon

Correspondence Authors:
Hyungjin Eoh,Jin-Woo Bae,Eun-Kyeong Jo

All Authors:
Young Jae Kim,June-Young Lee,Jae Jin Lee,Sang Min Jeon,Prashanta Silwal,In Soo Kim,Hyeon Ji Kim,Cho Rong Park,Chaeuk Chung,Jeong Eun Han,Jee-Won Choi,Euon Jung Tak,Ji-Ho Yoo,Su-Won Jeong,Do-Yeon Kim,Warisa Ketphan,Su-Young Kim,Byung Woo Jhun,Jake Whang,Jin-Man Kim,Hyungjin Eoh,Jin-Woo Bae,Eun-Kyeong Jo

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