Impact of the repurposed drug thonzonium bromide on host oral-gut microbiomes.
Impact of the repurposed drug thonzonium bromide on host oral-gut microbiomes.
复制标题
DOI：
10.1038/s41522-020-00181-5
复制
发表时间：
2021-01-22
影响因子：
9.2
通讯作者：
Koo H
中科院分区：
文献类型：
--
作者：
Simon-Soro A;Kim D;Li Y;Liu Y;Ito T;Sims KR Jr;Benoit DSW;Bittinger K;Koo H
药物再利用是开发新型治疗应用的可行策略。然而，其在口腔治疗中的潜在用途及其对宿主微生物群的影响仍未得到充分探索。在这里，我们评估了局部口服一种经fda批准的药物——硫唑溴铵对大鼠龋齿模型胃肠道微生物群和宿主组织的影响，该模型旨在减少与蛀牙相关的交叉污染。使用该模型，我们概括了反映人类微生物组概况的身体部位微生物群。口腔微生物群受到罗氏菌和微孔菌特异性破坏处理的干扰，但不影响粪便微生物群的总体组成。然而，使用嵌套性和机器学习确定了口腔-肠道微生物相互作用中的干扰，显示肠道微生物群中口腔类群Sutterella的共享增加。宿主组织分析显示溴唑铵对牙齿的龋齿减少无细胞毒性作用，表明口服时的生物活性和生物相容性。总之，我们证明了口服治疗如何使用重新利用的药物引起局部微生物干扰和治疗效果，同时促进体内下肠道特定口腔物种的周转。
Drug repurposing is a feasible strategy for the development of novel therapeutic applications. However, its potential use for oral treatments and impact on host microbiota remain underexplored. Here, we assessed the influences of topical oral applications of a repurposed FDA-approved drug, thonzonium bromide, on gastrointestinal microbiomes and host tissues in a rat model of dental caries designed to reduce cross-contamination associated with coprophagy. Using this model, we recapitulated the body site microbiota that mirrored the human microbiome profile. Oral microbiota was perturbed by the treatments with specific disruption of Rothia and Veillonella without affecting the global composition of the fecal microbiome. However, disturbances in the oral-gut microbial interactions were identified using nestedness and machine learning, showing increased sharing of oral taxon Sutterella in the gut microbiota. Host-tissue analyses revealed caries reduction on teeth by thonzonium bromide without cytotoxic effects, indicating bioactivity and biocompatibility when used orally. Altogether, we demonstrate how an oral treatment using a repurposed drug causes localized microbial disturbances and therapeutic effects while promoting turnover of specific oral species in the lower gut in vivo.
登录
查看更多内容
影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
15.5
作者：
Kim D;Hofstaedter CE;Zhao C;Mattei L;Tanes C;Clarke E;Lauder A;Sherrill-Mix S;Chehoud C;Kelsen J;Conrad M;Collman RG;Baldassano R;Bushman FD;Bittinger K
通讯作者：
Bittinger K
影响因子：
2.5
作者：
Bleich, Andre;Fox, James G.
通讯作者：
Fox, James G.
DOI：
10.1038/ismej.2012.8
发表时间：
2012-08
期刊：
The ISME journal
影响因子：
--
作者：
通讯作者：
--
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP