Biofilm Research Labs, Levy Center for Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Department of Orthodontics and divisions of Pediatric Dentistry & Community Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
NPJ Biofilms Microbiomes. 2021 Jan 22;7(1):7. doi: 10.1038/s41522-020-00181-5.
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.
药物再利用是开发新的治疗应用的可行策略。然而，其在口服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，我们评估了局部口腔应用一种经过重新利用的 FDA 批准药物——溴化硫柳汞对龋齿大鼠模型中胃肠道微生物群和宿主组织的影响，该模型旨在减少与食粪相关的交叉污染。使用这种模型，我们重现了与人类微生物组特征相匹配的体部位微生物群。口腔微生物群受到治疗的干扰，特定地破坏了罗特氏菌属和韦荣氏球菌属，而不会影响粪便微生物群的整体组成。然而，使用嵌套和机器学习识别出了口腔-肠道微生物相互作用的干扰，表明肠道微生物群中口腔分类群萨特氏菌的共享增加。宿主组织分析显示，溴化硫柳汞可减少牙齿龋齿，且无细胞毒性作用，表明其口服使用具有生物活性和生物相容性。总的来说，我们展示了一种使用重新利用药物的口服治疗如何在体内引起局部微生物紊乱和治疗效果，同时促进特定口腔物种在下肠道的更替。
