16s rRNA Sequencing Reveals Dynamic Oropharyngeal Microbiota Signatures in Different Stages of Mycobacterium tuberculosis Infection

Understanding the dynamics of the upper respiratory tract microbiota is crucial for the diagnosis and treatment of Tuberculosis patients. This study investigates the changes in the oropharyngeal microbiota during Mycobacterium tuberculosis (MTB) infection and its potential role in TB progression. Here, we investigated changes in the oropharyngeal microbiota in active pulmonary tuberculosis (PTB) patients and their close contacts. Based on the bacteriological examination results, we divided the PTB patients into the bacteriologically negative (BN) group and the bacteriologically confirmed (BC) group. According to the negative or strongly positive results of the tuberculin skin test, the close contacts were divided into the healthy control (HC) group and the latent TB infection (LTBI) group. No significant a diversity differences were observed among HC, LTBI, BN and BC. BN and BC differed significantly compared to HC in B diversity. The abundance of Proteobacteria differed between HC and BN and BC while Haemophilus was lower in BC than HC. LEfSe analysis revealed progressive enrichment of Dialister and Megasphaera from HC to BC, with reduced Haemophilus and Neisseria. Based on the imaging characteristics and clinical manifestations, PTB patients were further classified into Hole and Non Hole groups, Severe-TB) and Moderate TB groups, as well as Subclinical-TB and Clinical TB groups. Within these subgroups, a diversity was lower in the Clinical-TB compared to Subclinical TB. LEfSe analysis revealed enrichment of Staphylococcus in Severe TB compared to Moderate TB and Lactobacillus was enriched in Clinical-TB compared to Subclinical TB. Our study provides a systematic profile of oropharyngeal microbiota alterations across different stages of Mtb infection and in TB progression, suggesting that the changes in the oropharyngeal microbiota may be related to the natural course of the disease and may play a certain role in the occurrence and development of the disease, providing potential ideas for improving diagnostic and therapeutic strategies.