Arginine-mediated gut microbiome remodeling promotes host pulmonary immune defense against nontuberculous mycobacterial infection
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-12-01
|
| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2022.2073132 |
| _version_ | 1811246620139847680 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Young Jae Kim |
| collection | DOAJ |
| description | 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_indexed | 2024-04-12T14:56:24Z |
| format | Article |
| id | doaj.art-ab75d70c3de24f93897eb70d1a5cedb8 |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2024-04-12T14:56:24Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-ab75d70c3de24f93897eb70d1a5cedb82022-12-22T03:28:13ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2073132Arginine-mediated gut microbiome remodeling promotes host pulmonary immune defense against nontuberculous mycobacterial infectionYoung Jae Kim0June-Young Lee1Jae Jin Lee2Sang Min Jeon3Prashanta Silwal4In Soo Kim5Hyeon Ji Kim6Cho Rong Park7Chaeuk Chung8Jeong Eun Han9Jee-Won Choi10Euon Jung Tak11Ji-Ho Yoo12Su-Won Jeong13Do-Yeon Kim14Warisa Ketphan15Su-Young Kim16Byung Woo Jhun17Jake Whang18Jin-Man Kim19Hyungjin Eoh20Jin-Woo Bae21Eun-Kyeong Jo22Department of Microbiology, Chungnam National University School of Medicine Daejeon, KoreaDepartment of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul, KoreaDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California CA, USADepartment of Microbiology, Chungnam National University School of Medicine Daejeon, KoreaDepartment of Microbiology, Chungnam National University School of Medicine Daejeon, KoreaDepartment of Microbiology, Chungnam National University School of Medicine Daejeon, KoreaDepartment of Microbiology, Chungnam National University School of Medicine Daejeon, KoreaDepartment of Microbiology, Chungnam National University School of Medicine Daejeon, KoreaInfection Control Convergence Research Center, Chungnam National University School of Medicine Daejeon, KoreaDepartment of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul, KoreaDepartment of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul, KoreaDepartment of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul, KoreaDepartment of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, KoreaDepartment of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul, KoreaDepartment of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul, KoreaDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California CA, USADivision of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul, South KoreaDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul, South KoreaKorea Mycobacterium Resource Center (KMRC) & Basic Research Section, The Korean Institute of Tuberculosis (KIT), Cheongju, KoreaDepartment of Pathology, Chungnam National University School of Medicine, Daejeon, KoreaDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California CA, USADepartment of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul, KoreaDepartment of Microbiology, Chungnam National University School of Medicine Daejeon, KoreaNontuberculous 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.https://www.tandfonline.com/doi/10.1080/19490976.2022.2073132Nontuberculous mycobacterial-argininehost defensegut microbiota |
| spellingShingle | 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 Arginine-mediated gut microbiome remodeling promotes host pulmonary immune defense against nontuberculous mycobacterial infection Gut Microbes Nontuberculous mycobacteria l-arginine host defense gut microbiota |
| title | Arginine-mediated gut microbiome remodeling promotes host pulmonary immune defense against nontuberculous mycobacterial infection |
| title_full | Arginine-mediated gut microbiome remodeling promotes host pulmonary immune defense against nontuberculous mycobacterial infection |
| title_fullStr | Arginine-mediated gut microbiome remodeling promotes host pulmonary immune defense against nontuberculous mycobacterial infection |
| title_full_unstemmed | Arginine-mediated gut microbiome remodeling promotes host pulmonary immune defense against nontuberculous mycobacterial infection |
| title_short | Arginine-mediated gut microbiome remodeling promotes host pulmonary immune defense against nontuberculous mycobacterial infection |
| title_sort | arginine mediated gut microbiome remodeling promotes host pulmonary immune defense against nontuberculous mycobacterial infection |
| topic | Nontuberculous mycobacteria l-arginine host defense gut microbiota |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2022.2073132 |
| work_keys_str_mv | AT youngjaekim argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT juneyounglee argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT jaejinlee argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT sangminjeon argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT prashantasilwal argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT insookim argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT hyeonjikim argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT chorongpark argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT chaeukchung argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT jeongeunhan argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT jeewonchoi argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT euonjungtak argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT jihoyoo argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT suwonjeong argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT doyeonkim argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT warisaketphan argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT suyoungkim argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT byungwoojhun argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT jakewhang argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT jinmankim argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT hyungjineoh argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT jinwoobae argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection AT eunkyeongjo argininemediatedgutmicrobiomeremodelingpromoteshostpulmonaryimmunedefenseagainstnontuberculousmycobacterialinfection |