Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 50, Issue 12, Pages 1976-1987Publisher
WILEY
DOI: 10.1002/eji.202048556
Keywords
antibiotics; innate immunity; intestinal microbiota; isoniazid; tuberculosis; T cells
Categories
Funding
- Council of Scientific and Industrial Research (CSIR)
- Department of Biotechnology (DBT), Ministry of Science and Technology, India (DBT) [GAP 103]
- DBT-fellowship
- CSIR fellowship
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Tuberculosis (TB) continues to remain a global threat due to the emergence of drug-resistantMycobacterium tuberculosis(Mtb) strains and toxicity associated with TB drugs. Intestinal microbiota has been reported to affect the host response to immunotherapy and drugs. However, how it affects the potency of first-line TB drug isoniazid (INH) is largely unknown. Here, we examined the impact of gut microbial dysbiosis on INH efficiency to killMtb. In this study, we employed in vivo mouse model, pretreated with broad-spectrum antibiotics (Abx) cocktail to disrupt their intestinal microbial population prior toMtbinfection and subsequent INH therapy. We demonstrated that microbiota disruption results in the impairment of INH-mediatedMtbclearance, and aggravated TB-associated tissue pathology. Further, it suppressed the innate immunity and reduced CD4 T-cell response againstMtb. Interestingly, a distinct shift of gut microbial profile was noted with abundance ofEnterococcusand reduction ofLactobacillusandBifidobacteriumpopulation. Our results show that the intestinal microbiota is crucial determinant in efficacy of INH to killMtband impacts the host immune response against infection. This work provides an intriguing insight into the potential links between host gut microbiota and potency of INH.
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