The Microbiota of Human Lung of Pulmonary Tuberculosis and the Alteration Caused by Anti-tuberculosis Drugs

Abstract

An in-depth understanding of the lung microbiota in tuberculosis (TB) infection could provide optimal strategies for the prophylaxis, diagnosis, and treatment of the disease. Only a few studies have investigated the impact of Mycobacterium tuberculosis (Mtb) infection and anti-TB treatment on the lung microbiota. Bronchoalveolar lavage fluid and blood samples were collected from 23 active TB patients (TBZ), 17 latent tuberculosis infection patients (LTBI), 13 healthy controls (HC), and 14 active TB patients with 1-month anti-TB therapy (TBM) for 16S RNA sequencing and serological indexes, respectively. Low body mass index, albumin, and total triglyceride levels were detected in TBZ. Pulmonary Mtb infection led to a minor decrease in the alpha diversity of the lung microbiota in TBZ than HC, but a significant difference was noted in beta diversity. Subsequently, anti-TB therapy caused a rapid alteration in the lung community structure due to reduced alpha and beta diversity. Proteobacteria were abundant in TBZ samples, while Firmicutes was predominant in the LITB and HC samples. Lactobacillus and Subdoligranulum (genera) were the most unique in the LTBI and HC group, respectively. The TBM group showed the most predominant abundance of Bacteroides, Oscillospira, and Ruminococcus (genera). Functional pathways, such as indole alkaloid biosynthesis, Wnt signaling pathway, endocytosis, and metabolism of xenobiotics by cytochrome P450, significantly decreased in the TBM group compared with TBZ group. Pulmonary TB and anti-TB treatment caused a distinct dysbiosis of the lung microbiome. The current findings suggested potential links between the lung microbiota and TB onset, progression, and treatment.