Anti-tuberculosis effect of microbiome therapeutic PMC205 in extensively drug-resistant pulmonary tuberculosis in vivo

• In a lethal XDR pulmonary tuberculosis mouse model, administration of PMC205 increases the survival rate from 0% to 100%. • The mortality reduction effect of PMC205 was associated with restoration of disrupted lung microflora, increased butyric acid, and suppression of excessive inflammation. • PMC205 has the effect of lowering the burden of Mycobacterium tuberculosis in the lungs in an 8-month latent tuberculosis model. • The inhibition of M. tuberculosis by PMC205 is the result of promoting autophagy. • Therefore, PMC205 can be a microbiome therapeutic candidate for drug-resistant tuberculosis. Tuberculosis is a highly contagious disease caused by Mycobacterium tuberculosis , and the increase in antibiotic resistance threatens humankind. Therefore, there is an urgent need to develop new anti-tuberculosis drugs that can overcome the limitations of existing drugs. Here, we report the anti-tuberculosis effect of microbiome therapeutic PMC205, a strain of Bacillus subtilis . The anti-tuberculosis activity of probiotics was evaluated in mouse models of lethal and latent pulmonary tuberculosis induced by high or low-dose infection of the extensively drug-resistant strain. Probiotics were administered by inhalation, and the burden of M. tuberculosis in the lungs, along with mortality and clinical observations, were monitored for 12 weeks and 8 months, respectively. For an in-depth understanding, analysis of the microbiome and inflammatory profile of the lung microenvironment and induction of autophagy in vitro were explored. After inhalation administration of PMC205 for 3 months, the survival rate was 100%, unlike all deaths in the saline-treated group, and the burden of M. tuberculosis in the lungs was reduced by log 1.3 in the 8-month latent tuberculosis model. Moreover, PMC205 induced recovery of disrupted lung microflora, increased butyric acid, and suppressed excessive inflammation. It also promoted autophagy. These results confirm PMC205’s anti-tuberculosis effect, suggesting that it can be developed as an adjuvant to current antibiotic therapy to solve the drug-resistant tuberculosis problem.