微生物群
抗生素耐药性
抗生素
生物
微生物学
共生
抗菌剂
失调
殖民抵抗
抗药性
免疫学
细菌
生物信息学
遗传学
作者
Shakti Bhattarai,Mingmei Du,Abigail L. Zeamer,Benedikt M Mortzfeld,Tasia D. Kellogg,Firat Kaya,Anna Binyamin,James Bean,Matthew Zimmerman,Gertrude Mardi,Stalz Charles Vilbrun,Kathleen F. Walsh,Daniel W. Fitzgerald,Michael S. Glickman,Vanni Bucci
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2024-01-17
卷期号:16 (730)
被引量:1
标识
DOI:10.1126/scitranslmed.adi9711
摘要
Despite their therapeutic benefits, antibiotics exert collateral damage on the microbiome and promote antimicrobial resistance. However, the mechanisms governing microbiome recovery from antibiotics are poorly understood. Treatment of Mycobacterium tuberculosis , the world’s most common infection, represents the longest antimicrobial exposure in humans. Here, we investigate gut microbiome dynamics over 20 months of multidrug-resistant tuberculosis (TB) and 6 months of drug-sensitive TB treatment in humans. We find that gut microbiome dynamics and TB clearance are shared predictive cofactors of the resolution of TB-driven inflammation. The initial severe taxonomic and functional microbiome disruption, pathobiont domination, and enhancement of antibiotic resistance that initially accompanied long-term antibiotics were countered by later recovery of commensals. This resilience was driven by the competing evolution of antimicrobial resistance mutations in pathobionts and commensals, with commensal strains with resistance mutations reestablishing dominance. Fecal-microbiota transplantation of the antibiotic-resistant commensal microbiome in mice recapitulated resistance to further antibiotic disruption. These findings demonstrate that antimicrobial resistance mutations in commensals can have paradoxically beneficial effects by promoting microbiome resilience to antimicrobials and identify microbiome dynamics as a predictor of disease resolution in antibiotic therapy of a chronic infection.
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