TY  - INPR
N1  - Copyright of this article belongs to Wiley.
ID  - open2596
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1002/eji.202048556
A1  - Negi, Shikha
A1  - Pahari, Susanta
A1  - Bashir, Hilal
A1  - Agrewala, J N
Y1  - 2020/07/16/
N2  - 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.
PB  - Wiley
JF  - European journal of immunology
KW  - antibiotics; innate immunity; intestinal microbiota; isoniazid; tuberculosis; T cells
SN  - 0014-2980
TI  - Intestinal microbiota disruption limits the isoniazid mediated clearance ofMycobacterium tuberculosisin mice
ER  -