Gut microbiota dysbiosis-related susceptibility to nontuberculous mycobacterial lung disease

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.

Figure 1.

Gut microbiota dysbiosis in NTM-LD patients.

Figure 2.

P. copri predominantly induce TLR2 pathway and NTM-LD patients had compromised TLR2 activation activity.

Figure 3.

Gut microbiota dysbiosis and compromised TLR2 activation activity in mice receiving four antibiotics.

Figure 4.

Transcriptomic analysis of lung tissues of ABX mice.

Figure 5.

Administration of TLR2 agonist or treatment of P. copri restored immune response and ameliorated NTM-LD.

Figure 6.

Administration of capsular polysaccharide of P. copri ameliorated NTM-LD.