Abstract
Mycobacterium tuberculosis, the cause of Tuberculosis (TB), infects one third of the world’s population and causes substantial mortality worldwide. In its shortest format, treatment of TB requires six months of multidrug therapy with a mixture of broad spectrum and mycobacterial specific antibiotics, and treatment of multidrug resistant TB is longer. The widespread use of this regimen makes this one of the largest exposures of humans to antimicrobials, yet the effects of TB treatment on intestinal microbiome composition and long-term stability are unknown. We compared the microbiome composition, assessed by both 16S rDNA and metagenomic DNA sequencing, of TB cases during antimycobacterial treatment and following cure by 6 months of antibiotics. TB treatment does not perturb overall diversity, but nonetheless dramatically depletes multiple immunologically significant commensal bacteria. The microbiomic perturbation of TB therapy can persist for at least 1.2 years, indicating that the effects of TB treatment are long lasting. These results demonstrate that TB treatment has dramatic effects on the intestinal microbiome and highlight unexpected durable consequences of treatment for the world’s most common infection on human ecology.
Highlights
Each year, up to 3–4% of all deaths worldwide from any cause are attributable to infection with the bacterial pathogen Mycobacterium tuberculosis (Mtb), the causative agent of Tuberculosis (TB) disease, which amounts to almost 5,000 TB-related deaths each day[1]
Antimycobacterial treatment alters intestinal microbiota taxonomic composition during treatment without affecting overall diversity. It is currently unknown if and how the standard regimen of antimycobacterial HRZE therapy affects the taxonomic composition of the intestinal microbiota, as none of these drugs have been studied, alone or in combination, for their effects in humans
We present the first characterization of the short and long term effects of standard HRZE TB antibiotic treatment on the intestinal microbiome
Summary
Up to 3–4% of all deaths worldwide from any cause are attributable to infection with the bacterial pathogen Mycobacterium tuberculosis (Mtb), the causative agent of Tuberculosis (TB) disease, which amounts to almost 5,000 TB-related deaths each day[1]. Individuals with germline mutations in pathways involved in controlling mycobacterial infection, such as IFNγ and TNFα, have an increased risk of active TB disease[3] Despite these examples, known immune deficiencies are not sufficient to explain why the incidence of new active TB cases hovers over 10 million people each year, with a mortality rate between 1.5–2 million people[1]. Of the four standard TB antibiotics used in “short course” treatment (HRZE), only Rifampin, which inhibits bacterial RNA polymerase, is a broad-spectrum antimicrobial that is used for non-mycobacterial infections The effects of this prolonged antibiotic regimen on the intestinal microbiota are unknown
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