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Does tuberculosis treatment increase the risk of re-infection?

A recent study looked into how anti-tuberculosis drugs might affect the microbiota and increase the risk of re-infection.

 

Tuberculosis is one of the oldest diseases known to humans. A microbe called Mycobacterium tuberculosis causes and spreads this illness in the population. With time, this germ has evolved and adapted to survive within our body.

The World Health Organization estimates that about one-third of the world population hosts M. tuberculosis. This bacterium usually targets the lungs and can develop more than a single infection. Once in contact with the human body, M. tuberculosis will develop a primary infection.

Primary infections usually produce a few or no symptoms at all before resolving. Despite the positive outcome, this germ can survive and lie dormant within the body for many years. Active tuberculosis appears when the bacterium reactivates once it finds optimal conditions.

Diagnosis of tuberculosis is challenging and treatment is complex

The diagnosis of tuberculosis is not easy, and it can be a major challenge in some cases. The symptoms of this disease can be very similar to those caused by other respiratory as well as non-respiratory illnesses.

Laboratory methods for diagnosis face challenges such as the very slow growth rate of this germ and that some individuals might be less sensitive than others to the skin test. Treatment of tuberculosis uses drugs that can kill the bacterium responsible for the infection. Therapies might be complex, as they require the use of multiple drugs at once for a period that extends to several months.

The length of treatment complicates adherence to the therapy regime, while the use of these substances can have toxic effects on the liver. Antibiotics are effective at killing germs, but they also disrupt the human microbiota, which consists of microbes living within our body that are beneficial to us. Research studies found antibiotics to increase the risk of infectious diseases in patients by affecting the microbiota.

Tuberculosis treatment might have adverse effects on the gut microbiota

We do not know much about the effects of tuberculosis treatment on the intestinal microbiota. For this reason, a recent study looked at how these drugs interact with the microbiota and how this interaction might influence the risk of re-infection by M. tuberculosis. Their results are published in Mucosal Immunology.

The researchers first studied the effects of anti-tuberculosis drugs on the microbiota of mice. They selected isoniazid (INH), pyrazinamide (PYZ), and rifampicin (RIF), which are among the most commonly used medications for this disease. INH and PYZ specifically kill the mycobacterium by attacking its cell wall, while RIF is a less specific antibiotic and is effective against multiple groups of germs.

Scientists treated mice either with a combination of INH and PYZ or with RIF for eight weeks, and then looked at the gut microbiota composition. They found that both treatments caused changes in the microbiota, but the combination of INH and PYZ also made the mice more vulnerable to infection in comparison to animals treated with just RIF.

Changes in the gut microbiota affect the immune defences in the lungs

The researchers then focused their efforts into finding a connection between the intestinal microbiota and the immune mechanisms in the lungs, the organs most commonly hit by tuberculosis. They were able to prove that the effects of INH/PYZ treatment on the gut microbiota of mice altered the metabolism of immune cells in the lungs called alveolar macrophages. Alveolar macrophages are the first line of defence in the lungs against the mycobacterium. Altered metabolism of these cells associated with a failure in containing the infection.

Future research will investigate the effects of tuberculosis treatment on the microbiota of human patients

In conclusion, this study looked at the effects of anti-tuberculosis drugs on the intestinal microbiota of mice. The scientists found that the combination of INH and PYZ drugs not only affects the microbial community in the intestine but also increases the chances of infection by M. tuberculosis. Alterations of the microbial community cause metabolic changes in immune cells in the lungs such that they fail to contain the dangerous bacteria.

More work is necessary to uncover the specific mechanisms that connect the gut microbiota to the immune system in the lungs. However, this study paves the way for future research that will look into the effects of tuberculosis treatment on the microbiota of human patients.

Written by Raffaele Camasta, PhD

References:

  1. Khan, N., Mendonca, L., Dhariwal, A., Fontes, G., Menzies, D., Xia, J., Divangahi, M., & King, I. L. (2019). Intestinal dysbiosis compromises alveolar macrophage immunity to Mycobacterium tuberculosis. Mucosal Immunology.
  2. Anti-TB drugs can increase risk of TB re-infection. https://www.eurekalert.org/pub_releases/2019-03/mu-ad032219.php
  3. Lyon, S. M., & Rossman, M. D. (2017). Pulmonary Tuberculosis. Microbiology Spectrum, 5(1), 1–13.
  4. Leung, C. C., Lange, C., & Zhang, Y. (2013). Tuberculosis: Current state of knowledge: An epilogue. Respirology. 18(7), 1047-1055.
  5. Dobbs, T. E., & Webb, R. M. (2017). Chemotherapy of Tuberculosis. Microbiology Spectrum, 5(2), 1–16,
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