The Microbiome and the Gut-Liver-Brain Axis for Central Nervous System Clinical Pharmacology: Challenges in Specifying and Integrating In Vitro and In Silico Models.
The Microbiome and the Gut-Liver-Brain Axis for Central Nervous System Clinical Pharmacology: Challenges in Specifying and Integrating In Vitro and In Silico Models.
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DOI：
10.1002/cpt.1870
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发表时间：
2020-11
影响因子：
6.7
通讯作者：
Wikswo JP
中科院分区：
文献类型：
--
作者：
Hawkins KG;Casolaro C;Brown JA;Edwards DA;Wikswo JP
将微生物群整合到临床药理学，环境毒理学和阿片类药物研究中的复杂性源于人类与其许多微生物群（特别是肠道微生物群）之间的双向和多尺度相互作用。微生物和每种微生物群都受到不同的中心法则的支配，遗传学影响转录组学，蛋白质组学和代谢组学。每个微生物群的代谢组都有差异地调节其自身和宿主的多组学。外源化合物（例如，药物和毒素），通常影响宿主多组学，与微生物群多组学不同，改变了药物疗效和毒性之间的平衡。宿主-微生物群连接的复杂性已经通过目前的体外细菌培养和体内小鼠模型方法得到了证实，但它们未能阐明机制细节。总之，体外器官芯片微生理学模型，多组学和计算机计算模型有可能补充已建立的方法，帮助临床药理学家和环境毒理学家解开肠道微生物群与宿主健康和疾病之间的无数联系。
The complexity of integrating microbiota into clinical pharmacology, environmental toxicology, and opioid studies arises from bidirectional and multiscale interactions between humans and their many microbiota, notably those of the gut. Hosts and each microbiota are governed by distinct central dogmas, with genetics influencing transcriptomics, proteomics, and metabolomics. Each microbiota's metabolome differentially modulates its own and the host's multi‐omics. Exogenous compounds (e.g., drugs and toxins), often affect host multi‐omics differently than microbiota multi‐omics, shifting the balance between drug efficacy and toxicity. The complexity of the host‐microbiota connection has been informed by current methods of in vitro bacterial cultures and in vivo mouse models, but they fail to elucidate mechanistic details. Together, in vitro organ‐on‐chip microphysiological models, multi‐omics, and in silico computational models have the potential to supplement the established methods to help clinical pharmacologists and environmental toxicologists unravel the myriad of connections between the gut microbiota and host health and disease.
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影响因子：
24.5
作者：
Cani PD
通讯作者：
Cani PD
影响因子：
64.8
作者：
CRICK, F
通讯作者：
CRICK, F
DOI：
10.3390/s90302117
发表时间：
2009
期刊：
Sensors (Basel, Switzerland)
影响因子：
--
作者：
Eklund SE;Thompson RG;Snider RM;Carney CK;Wright DW;Wikswo J;Cliffel DE
通讯作者：
Cliffel DE
DOI：
10.1073/pnas.0904489106
发表时间：
2009-08-25
影响因子：
11.1
作者：
Clayton, T. Andrew;Baker, David;Nicholson, Jeremy K.
通讯作者：
Nicholson, Jeremy K.
影响因子：
2.3
作者：
Clapp M;Aurora N;Herrera L;Bhatia M;Wilen E;Wakefield S
通讯作者：
Wakefield S