The Clinical Drug Ebselen Attenuates Inflammation and Promotes Microbiome Recovery in Mice after Antibiotic Treatment for CDI
Autor: | Matthew Bogyo, Justin L. Sonnenburg, Sebastian Loscher, Martina Tholen, Kristina Oresic Bender, Megan Garland, Will Van Treuren, Andrew J. Hryckowian |
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Rok vydání: | 2020 |
Předmět: |
Male
Toxic megacolon vancomycin microbiome recovery Isoindoles microbiome diversity General Biochemistry Genetics and Molecular Biology Article chemistry.chemical_compound Mice Cricetinae Organoselenium Compounds medicine Animals antibitoic treatment Microbiome Colitis Enterocolitis Pseudomembranous Inflammation lcsh:R5-920 Bacterial disease Mesocricetus Ebselen business.industry Clostridioides difficile clostridium difficile Clostridium difficile medicine.disease Gastrointestinal Microbiome Disease Models Animal chemistry Immunology Clostridium Infections Vancomycin Dysbiosis Female ebselen lcsh:Medicine (General) business medicine.drug |
Zdroj: | Cell reports medicine Cell Reports Medicine, Vol 1, Iss 1, Pp 100005-(2020) |
ISSN: | 2666-3791 |
Popis: | SUMMARY 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 antibiotic-induced 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. In Brief Garland et al. show in a hamster model that the safe-in-human molecule ebselen, with its anti-toxin and anti-inflammatory activity, decreases colitis, and prevents reoccurrence of C. difficile infection. Ebselen also helps to reduce inflammation and promote recovery of microbiome diversity after antibiotic treatment in mice. Graphical Abstract |
Databáze: | OpenAIRE |
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