Longitudinal profiling reveals a persistent intestinal dysbiosis triggered by conventional anti-tuberculosis therapy.
Longitudinal profiling reveals a persistent intestinal dysbiosis triggered by conventional anti-tuberculosis therapy.
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DOI：
10.1186/s40168-017-0286-2
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发表时间：
2017-07-07
期刊：
影响因子：
15.5
通讯作者：
Sher A
中科院分区：
文献类型：
--
作者：
Namasivayam S;Maiga M;Yuan W;Thovarai V;Costa DL;Mittereder LR;Wipperman MF;Glickman MS;Dzutsev A;Trinchieri G;Sher A
结核分枝杆菌（Mtb）感染的有效治疗需要至少6个月的每日多种口服抗生素治疗。尽管这种药物方案每年在全球范围内对数百万人进行给药，但这种强化抗菌治疗对宿主微生物组的影响从未得到正式研究。在这里，我们通过16 S rRNA测序表征了常规异烟肼-利福平-吡嗪酰胺（HRZ）TB药物给药对结核分枝杆菌感染小鼠肠道微生物群多样性和组成的纵向结果。我们还研究了每种抗生素单独使用和不同组合的效果。虽然HRZ治疗仅引起微生物多样性的短暂减少，但它引发了群落结构的显著、立即和可重现的改变，这种改变持续整个治疗过程和停止治疗后至少3个月。梭菌目的成员是在处理期间相对频率降低的类群之一，而紫单胞菌科在处理后显著增加。比较单药治疗和不同联合治疗的实验确定利福平是观察到的由HRZ鸡尾酒诱导的变化的主要驱动因素，但也揭示了异烟肼和吡嗪酰胺在某些药物配对中的意外作用。该报告首次详细分析了抗结核治疗引起的肠道微生物群的纵向变化。重要的是，许多受影响的分类群先前已在其他系统中显示与免疫功能的修饰相关。总之，我们的研究结果表明，在传统的结核病治疗中使用的抗生素诱导了一种独特的和持久的生态失调。此外，他们建立了一个小鼠模型，用于研究这种生态失调对宿主抗性和生理学的潜在影响。本文的在线版本（doi：10.1186/s40168-017-0286-2）包含补充材料，可供授权用户使用。
Effective treatment of Mycobacterium tuberculosis (Mtb) infection requires at least 6 months of daily therapy with multiple orally administered antibiotics. Although this drug regimen is administered annually to millions worldwide, the impact of such intensive antimicrobial treatment on the host microbiome has never been formally investigated. Here, we characterized the longitudinal outcome of conventional isoniazid-rifampin-pyrazinamide (HRZ) TB drug administration on the diversity and composition of the intestinal microbiota in Mtb-infected mice by means of 16S rRNA sequencing. We also investigated the effects of each of the individual antibiotics alone and in different combinations. While inducing only a transient decrease in microbial diversity, HRZ treatment triggered a marked, immediate and reproducible alteration in community structure that persisted for the entire course of therapy and for at least 3 months following its cessation. Members of order Clostridiales were among the taxa that decreased in relative frequencies during treatment and family Porphyromonadaceae significantly increased post treatment. Experiments comparing monotherapy and different combination therapies identified rifampin as the major driver of the observed alterations induced by the HRZ cocktail but also revealed unexpected effects of isoniazid and pyrazinamide in certain drug pairings. This report provides the first detailed analysis of the longitudinal changes in the intestinal microbiota due to anti-tuberculosis therapy. Importantly, many of the affected taxa have been previously shown in other systems to be associated with modifications in immunologic function. Together, our findings reveal that the antibiotics used in conventional TB treatment induce a distinct and long lasting dysbiosis. In addition, they establish a murine model for studying the potential impact of this dysbiosis on host resistance and physiology. The online version of this article (doi:10.1186/s40168-017-0286-2) contains supplementary material, which is available to authorized users.
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影响因子：
5.2
作者：
Ahmad, Zahoor;Fraig, Mostafa M.;Karakousis, Petros C.
通讯作者：
Karakousis, Petros C.
影响因子：
--
作者：
BRISMAR, B;EDLUND, C;NORD, CE
通讯作者：
NORD, CE
影响因子：
64.5
作者：
Cox LM;Yamanishi S;Sohn J;Alekseyenko AV;Leung JM;Cho I;Kim SG;Li H;Gao Z;Mahana D;Zárate Rodriguez JG;Rogers AB;Robine N;Loke P;Blaser MJ
通讯作者：
Blaser MJ
影响因子：
6.7
作者：
Dickson RP;Huffnagle GB
通讯作者：
Huffnagle GB
影响因子：
64.8
作者：
Cho, Ilseung;Yamanishi, Shingo;Cox, Laura;Methe, Barbara A.;Zavadil, Jiri;Li, Kelvin;Gao, Zhan;Mahana, Douglas;Raju, Kartik;Teitler, Isabel;Li, Huilin;Alekseyenko, Alexander V.;Blaser, Martin J.
通讯作者：
Blaser, Martin J.