Gut microbiota dysbiosis-related susceptibility to nontuberculous mycobacterial lung disease

Gut Microbes. 2024 Jan-Dec;16(1):2361490. doi: 10.1080/19490976.2024.2361490. Epub 2024 Jun 11.

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.

Keywords: Gut microbiota dysbiosis; TLR2 activation; capsular polysaccharide; nontuberculous mycobacterial lung disease; prevotella copri.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Toll-Like Receptor 2
  • TLR2 protein, human

Grants and funding

We would like to express our thankfulness for funding provided from CORPD1J0053, CMRPD1J0333 and CMRPD1M0081 from Chang Gung Memorial Hospital, 109-2320-B-182-034-MY3, 109-2320-B-030-010, 111-2327-B-182-003, 109-2326-B-002-009-MY3, 111-2628-B-002 -031 -MY3 from National Science and Technology Council (NSTC), NHRI-EX108-10821SC, NHRI-EX109-10821SC, NHRI-EX110-10821SC, NHRI-EX111-10821SC, NHRI-EX112-11233SI, NHRI-EX113-11233SI from National Health Research Institute, NTUH 110-T07, 111-T0014, 112-E0014, 113-E0005 from National Taiwan University Hospital, Microbiota Research Center from Chang Gung University, and the Research Center for Emerging Viral Infections from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan and the Ministry of Science and Technology (MOST), Taiwan (MOST 111-2634-F-182-001).