The clinical drug candidate ebselen attenuates inflammation and promotes microbiome recovery after antibiotic treatment for Clostridium difficile infection
The clinical drug candidate ebselen attenuates inflammation and promotes microbiome recovery after antibiotic treatment for Clostridium difficile infection
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临床候选药物依布硒啉可减轻艰难梭菌感染抗生素治疗后的炎症并促进微生物组恢复
DOI：
10.1101/827329
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发表时间：
--
期刊：
影响因子：
--
通讯作者：
Bogyo M.
中科院分区：
文献类型：
--
作者：
Garland M;Hryckowian A;Tholen M;Loscher S;Van Treuren W;Oresic Bender K;Sonnenburg J.L;Bogyo M.
艰难梭菌感染（CDI）是一种肠道细菌性疾病，在世界范围内的流行率正在上升. difficilecapitalizes对肠道炎症和微生物菌群失调建立感染，症状范围从水样腹泻到毒性巨结肠。我们最近报道了安全的人体临床候选药物依布硒啉（NCT 03013400、NCT 01452607、NCT 00762671、NCT 02603081）对C.很难在这里，我们表明，依布硒啉治疗降低复发率，减少结肠炎的仓鼠复发模型的CDI。此外，依布硒啉治疗不会改变微生物组的多样性，但在健康和C.艰难梭菌感染的小鼠依布硒啉治疗后微生物组恢复增加与宿主来源的炎症标志物减少相关，表明依布硒啉的抗炎特性及其抗毒素功能有助于减轻CDI的主要临床挑战，包括复发、微生物生态失调和结肠炎。
Clostridium difficileinfection (CDI) is an enteric bacterial disease that is increasing in prevalence worldwide.C. difficilecapitalizes on gut inflammation and microbiome dysbiosis to establish infection, with symptoms ranging from watery diarrhea to toxic megacolon. We recently reported that the safe in human clinical drug candidate ebselen (NCT03013400, NCT01452607, NCT00762671, NCT02603081) has biochemical, cell-based andin vivoefficacy against the bacterial toxins ofC. difficile. Here, we show that ebselen treatment reduces recurrence rates and decreases colitis in a hamster relapse model of CDI. Furthermore, ebselen treatment does not alter microbiome diversity but promotes its recovery back to that of healthy controls after antibiotic-induced dysbiosis in both healthy andC. difficile-infected mice. This increased microbiome recovery upon ebselen treatment correlates with a decrease in host-derived inflammatory markers suggesting that the anti-inflammatory properties of ebselen, combined with its anti-toxin function, help to mitigate the major clinical challenges of CDI, including recurrence, microbial dysbiosis, and colitis.
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教师意见推荐缺乏膳食纤维的肠道微生物群会降低结肠粘液屏障并增强病原体的敏感性。
DOI：
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发表时间：
2019
期刊：
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
影响因子：
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作者：
Henry Lin;D. Lin
通讯作者：
D. Lin
影响因子：
4.3
作者：
Trifan A;Stanciu C;Girleanu I;Stoica OC;Singeap AM;Maxim R;Chiriac SA;Ciobica A;Boiculese L
通讯作者：
Boiculese L
影响因子：
29.4
作者：
Chen, Xinhua;Katchar, Kianoosh;Kelly, Ciaran P.
通讯作者：
Kelly, Ciaran P.
婴儿肠道微生物群的宏基因组学和发育。
DOI：
10.1111/j.1469-0691.2012.03876.x
发表时间：
2012
期刊：
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
影响因子：
--
作者：
Valles,Y;Gosalbes,MJ;deVries,LE;Abellan,JJ;Francino,MP
通讯作者：
Francino,MP
影响因子：
6.4
作者：
Khanna, Sahil;Pardi, Darrell S.;Hohmann, Elizabeth L.
通讯作者：
Hohmann, Elizabeth L.