Small molecule modulation of microbiota: a systems pharmacology perspective.
Small molecule modulation of microbiota: a systems pharmacology perspective.
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DOI：
10.1186/s12859-022-04941-2
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发表时间：
2022-09-29
影响因子：
3
通讯作者：
Xie, Lei
中科院分区：
文献类型：
--
作者：
Liu, Qiao;Lee, Bohyun;Xie, Lei
微生物与许多人类疾病有关，并影响药物疗效。小分子药物可能会根据患者个体的微生物组特征微调微生物区系，从而给生物医学带来革命性的变化。然而，在小分子微生物组药物发现方面的新兴努力继续遵循传统的“一药一靶一病”的过程。一种系统的药理学方法可以抑制微生物组中多种相互作用的致病物种，这可能提供一个有吸引力的替代解决方案。我们利用精选的微生物代谢物信息及其对宿主的影响，构建了一个以疾病为中心的微生物-微生物相互作用网络。为了准确预测微生物对人类健康和疾病的影响，我们提出了一种带重启的带符号随机游走算法。通过对微生物蛋白质的可药物和进化空间的调查，我们发现其中8%-10%的微生物蛋白质可以被现有的药物或类药物靶向，其中25%的微生物蛋白质与人类蛋白质具有同源性。我们证明，治疗糖尿病的药物可以成为微生物区系靶向治疗药物开发的先导化合物。我们进一步证明，特定存在于病原微生物中的潜在药物靶点是周质和细胞外膜蛋白。对微生物组网络多药理景观的系统研究可能为微生物组小分子药物的发现开辟一条新的途径。我们相信，将系统方法应用于多种药理研究，可能会发现新的药物疗法。网上版载有补充材料，可在10.1186/s12859-022-04941-2查阅。
Microbes are associated with many human diseases and influence drug efficacy. Small-molecule drugs may revolutionize biomedicine by fine-tuning the microbiota on the basis of individual patient microbiome signatures. However, emerging endeavors in small-molecule microbiome drug discovery continue to follow a conventional “one-drug-one-target-one-disease” process. A systematic pharmacology approach that would suppress multiple interacting pathogenic species in the microbiome, could offer an attractive alternative solution. We construct a disease-centric signed microbe–microbe interaction network using curated microbe metabolite information and their effects on host. We develop a Signed Random Walk with Restart algorithm for the accurate prediction of effect of microbes on human health and diseases. With a survey on the druggable and evolutionary space of microbe proteins, we find that 8–10% of them can be targeted by existing drugs or drug-like chemicals and that 25% of them have homologs to human proteins. We demonstrate that drugs for diabetes can be the lead compounds for development of microbiota-targeted therapeutics. We further show that the potential drug targets that specifically exist in pathogenic microbes are periplasmic and cellular outer membrane proteins. The systematic studies of the polypharmacological landscape of the microbiome network may open a new avenue for the small-molecule drug discovery of the microbiome. We believe that the application of systematic method on the polypharmacological investigation could lead to the discovery of novel drug therapies. The online version contains supplementary material available at 10.1186/s12859-022-04941-2.
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DOI：
10.1073/pnas.1502875112
发表时间：
2015-09-01
影响因子：
11.1
作者：
DiGiulio, Daniel B.;Callahan, Benjamin J.;Relman, David A.
通讯作者：
Relman, David A.
影响因子：
14.9
作者：
Gaulton A;Hersey A;Nowotka M;Bento AP;Chambers J;Mendez D;Mutowo P;Atkinson F;Bellis LJ;Cibrián-Uhalte E;Davies M;Dedman N;Karlsson A;Magariños MP;Overington JP;Papadatos G;Smit I;Leach AR
通讯作者：
Leach AR
影响因子：
64.8
作者：
Barton, Erik S.;White, Douglas W.;Virgin, Herbert W.
通讯作者：
Virgin, Herbert W.
抗生素抗性的综述：警报铃响。
DOI：
10.7759/cureus.1403
发表时间：
2017-06-28
期刊：
Cureus
影响因子：
--
作者：
Zaman SB;Hussain MA;Nye R;Mehta V;Mamun KT;Hossain N
通讯作者：
Hossain N
影响因子：
82.9
作者：
Fujimura, Kei E.;Sitarik, Alexandra R.;Haystad, Suzanne;Lin, Din L.;Levan, Sophia;Fadrosh, Douglas;Panzer, Ariane R.;LaMere, Brandon;Rackaityte, Elze;Lukacs, Nicholas W.;Wegienka, Ganesa;Boushey, Homer A.;Ownby, Dennis R.;Zoratti, Edward M.;Levin, Albert M.;Johnson, Christine C.;Lynch, Susan V.
通讯作者：
Lynch, Susan V.