Do you know there is more in you than just the TB germ?

Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the leading infectious diseases with more than 10 million active cases worldwide and approximately 25% of the world population being latently infected (WHO global tuberculosis report, 2018). TB is a disease with largest number of antibiotics used for treatment at one time. However post treatment the cure rate is around 85% for drug sensitive cases and 65% for drug resistant and 5% chances of relapse (Naidoo et al., 2019). While risk factors, improper adherence to treatment and development of resistance can explain some cases of treatment failures, the determinants for others remains unknown. Though traditionally TB studies have been focused on its single causative agent, emerging evidence suggests that multiple interactions between host, the TB germ and the organisms in our gut and lung (the microbiome) may play a major role in the disease process and outcomes and enable the shift between susceptibility and infection.

The collective total of microbial communities (bacterial, fungal, viral) inhabiting our body along with their genetic component sums up the human microbiome. The advances in the next generation sequencing and reducing costs have made it possible to study the various microbial communities that reside in specific sites in the human body. Studies have shown that the microbiome through the three axes (Gut-Brain, Gut-Liver and Gut-Lung), production of various metabolites,and involvement in nutrition, pathogenesis and immunology of the host plays an important role in health and disease. Throughout the lifetime of an individual many factors like dietary changes, infection followed by treatment, can bring about changes in the microbiome composition and function, thus establishing a state of disturbance. These disturbances can lead to reduced population of beneficial microbes and increase in the number of disease causing organisms. The few overlapping studies in the field of TB disease and microbiome have reported that the infection and its subsequent treatment causes similar and prolonged disturbance in the bacterial population in the gut. (Wipperman et al, 2017). However there is very little knowledge about the effect of TB infection on the organisms that are residents of the lung.

We are interested in understanding the effect of TB infection and early treatment with first line drugs on the bacteria that reside in the lungs (respiratory microbiome). The first line anti TB drugs consists of three narrow spectrums (mycobacterial specific) drugs — isoniazid, pyrazinamide and ethambutol — and one broad spectrum drug Rifampicin. The preliminary results from our studies, presented at TB Science 2019 in Hyderabad, showed that TB infection and treatment (up to two weeks) causes changes in the microbial and functional structure of respiratory microbiome. We observed that three days of anti-TB treatment suppressed the growth of beneficial organisms of Lactobacilli and Bifidobacterium species, while promoting the growth of harmful organisms (anaerobes) and increased expression of certain resistance factors. Though the consequences of changes in microbial structure are still being investigated we can speculate that disturbances in microbial community may have an effect on the immune system.

An improved understanding of the microbiomes association with tuberculosis will provide further insight into the disease especially in cases of treatment failures and relapse The microbiome tuberculosis crosstalk may also open up avenues to study interactions between microbiome and drug metabolism and or adverse effects.

References: -

· WHO global Tuberculosis report 2018

· Naidoo et al, Lancet Respir Med. 2019 Oct;7(10):892–906

· Wipperman et al, Sci Rep. 2017 Sep 7;7(1):10767