A study published in Mucosal Immunology by Drs. Irah King and Maziar Divangahi showed that anti-TB drugs ( anti-tuberculosis drugs) caused changes to gut microbiota, thereby compromising immunity. This then led to an increased susceptibility to Mycobacterium tuberculosis infection.
Current treatments for tuberculosis (TB) are very effective in controlling TB infection caused by Mycobacterium tuberculosis (Mtb). They don’t, however, always prevent reinfection. Why this happens is one of the long-standing questions in TB research.
Gut microbiota are critical to keeping us healthy; they help to digest food, combat pathogenic microbes and reinforce our immune system. Recent research has shown that chronic use of antibiotic leads to disruption of this community, which can in turn lead to dysregulation of the immune system. It remains unclear, however, whether changes in the composition of the microbes living in our gut have an influence on TB infection.
The research team treated mice with the most commonly used anti-TB drugs – isoniazid, rifampicin and pyrazinamide – for a period of eight weeks. They found that while all three drugs significantly altered the composition of the mice’s gut microbiome, only mice treated with isoniazid combined with pyrazinamide showed an increase in susceptibility to Mtb infection. Transplanting feces from healthy mice into animals treated with anti-TB drugs was sufficient to restore immunity to Mtb. The team also evaluated a number of lung cell types known to be important for resistance to Mtb infection. Following anti-TB treatment, alveolar macrophages, a type of immune cell located in the airways of mice and humans and the first cell to encounter Mtb upon infection, were compromised in their ability to kill Mtb.
“Anti-TB therapies have been incredibly efficient in controlling the TB epidemic by decreasing morbidity and mortality associated with Mtb. Now, this work provides a basis for novel therapeutic strategies exploiting the gut-lung axis in Mtb infection.’’ – Irah King
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Intestinal dysbiosis compromises alveolar macrophage immunity to Mycobacterium tuberculosis. Khan N, Mendonca L, Dhariwal A, Fontes G, Menzies D, Xia J, Divangahi M, King IL. Mucosal Immunol. 2019 May;12(3):772-783. doi: 10.1038/s41385-019-0147-3. Epub 2019 Feb 19. PMID: 30783183
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