The Clinical Drug Ebselen Attenuates Inflammation and Promotes Microbiome Recovery in Mice after Antibiotic Treatment for CDI
The Clinical Drug Ebselen Attenuates Inflammation and Promotes Microbiome Recovery in Mice after Antibiotic Treatment for CDI
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DOI：
10.1016/j.xcrm.2020.100005
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发表时间：
2020-04-21
影响因子：
14.3
通讯作者：
Bogyo, Matthew
中科院分区：
文献类型：
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作者：
Garland, Megan;Hryckowian, Andrew J.;Bogyo, Matthew
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增加。C.艰难梭菌利用肠道炎症和微生物群失调来建立感染，症状从水样腹泻到毒性巨结肠。我们报告了人体安全临床药物依布硒啉（ClinicalTrials.gov：NCT 03013400、NCT 01452607、NCT 00762671和NCT 02603081）对C.很难在这里，我们表明，依布硒啉治疗降低复发率和减少复发性CDI的仓鼠模型中的结肠炎。此外，依布硒啉治疗不会改变微生物组的多样性，并促进在健康和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与其抗毒素功能相结合，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 difficile infection (CDI) is an enteric bacterial disease that is increasing in prevalence worldwide. C. difficile capitalizes on gut inflammation and microbiome dysbiosis to establish infection, with symptoms ranging from watery diarrhea to toxic megacolon. We reported that the safe-in-human clinical drug ebselen (ClinicalTrials.gov: NCT03013400, NCT01452607, NCT00762671, and NCT02603081) has biochemical, cell-based, and in vivo efficacy against the toxins of C. difficile. Here, we show that ebselen treatment reduces recurrence rates and decreases colitis in a hamster model of relapsing CDI. Furthermore, ebselen treatment does not alter microbiome diversity and promotes recovery back to that of healthy controls after anti-bioticinduced dysbiosis in healthy and C. 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.