Sputum Microbiota Associated with New, Recurrent and Treatment Failure Tuberculosis

Jing Wu,Wenhong Zhang,Peng Cui,Jiazhen Chen,Jing Zhao,Lei He,Wei Liu,Min Zhu,Fuli Huang,Wenjie Wang,Yaojie Shen,Ying Zhang,Yan Zhang,Olivier Neyrolles

doi:10.1371/journal.pone.0083445

Abstract

Microbiota have recently been shown to be associated with many disease conditions. However, the microbiota associated with tuberculosis (TB) infection, recurrence and treatment outcome have not been systematically characterized. Here, we used high throughput 16S RNA sequencing to analyze the sputum microbiota associated with Mycobacterium tuberculosis infection and also to identify the microorganisms associated with different outcomes of TB treatment. We recruited 25 new TB patients, 30 recurrent TB patients and 20 TB patients with treatment failure, as well as 20 healthy controls. Streptococcus, Gramulicatella and Pseudomonas were more abundant in TB patients while Prevotella, Leptotrichia, Treponema, Catonella and Coprococcus were less abundant in TB patients than in the healthy controls. We found reduced frequency and abundance of some genera such as Bulleidia and Atopobium in recurrent TB patients compared with those in new TB patients. In addition, the ratio of Pseudomonas / Mycobacterium in recurrent TB was higher than that in new TB while the ratio of Treponema / Mycobacterium in recurrent TB was lower than that in new TB, indicating that disruption of these bacteria may be a risk factor of TB recurrence. Furthermore, Pseudomonas was more abundant and more frequently present in treatment failure patients than in cured new patients, and the ratio of Pseudomonas / Mycobacterium in treatment failure was higher than that in new TB. Our data suggest that the presence of certain bacteria and the disorder of lung microbiota may be associated with not only onset of TB but also its recurrence and treatment failure. These findings indicate that lung microbiota may play a role in pathogenesis and treatment outcome of TB and may need to be taken into consideration for improved treatment and control of TB in the future.

Highlights

Tuberculosis caused by Mycobacterium tuberculosis (Mtb) remains a leading infectious disease worldwide despite availability of chemotherapy and BCG vaccine
The present study has characterized microbiota in the sputa of TB patients associated with Mtb infection and the microorganisms associated with the different outcomes of treatment
We found that Pseudomonas is the only genus that is more abundant or more frequently present in TB treatment failure patients or recurrent TB than in new or cured TB patients and healthy controls (Figure 6, Table 2), and it is the only genus differentially existed between cured TB patients and treatment failure patients

Summary

Introduction

Tuberculosis caused by Mycobacterium tuberculosis (Mtb) remains a leading infectious disease worldwide despite availability of chemotherapy and BCG vaccine. One third of the world population, about 2 billion people, is latently infected with Mtb. In people with latent tuberculosis infection, the risk of becoming active tuberculosis is approximately 5% - 10% during the life time. When the immune system is compromised, such as co-infections with HIV, malnutrition and aging, latent infections can reactivate and develop into active disease [1]. TB can be cured with a cure rate of 85-95%, some patients are not cured and even cured patients can have relapse While many factors such as inadequate patient compliance and drug resistance are involved, they do not appear to explain all the treatment failures or relapse. It is possible that resident lung microbial community or microbiota may play a role in the disease reactivation and treatment outcome

Methods

Results

Conclusion