Butyrate enhances Clostridioides difficile sporulation in vitro.
Butyrate enhances Clostridioides difficile sporulation in vitro.
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DOI：
10.1128/jb.00138-23
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发表时间：
2023-09-26
影响因子：
3.2
通讯作者：
Seekatz, Anna M.
中科院分区：
文献类型：
--
作者：
Baldassare, Michelle A.;Bhattacharjee, Disha;Coles, Julian D.;Nelson, Sydney;Mccollum, C. Alexis;Seekatz, Anna M.
短链脂肪酸（SCFA）是细菌发酵的产物，有助于维持重要的肠道功能，如维持肠道屏障，细胞信号和免疫稳态。主要的SCFA乙酸盐、丙酸盐和丁酸盐已证明对宿主有益，包括其在减轻由病原体如艰难梭菌引起的感染中的重要性。尽管SCFAs在减轻C.艰难梭菌感染，它们对C. difficile仍然不清楚。通过一系列体外实验，我们研究了SCFAs如何影响C。艰难生长、孢子形成和毒素产生。与以前的研究类似，我们观察到丁酸盐降低了C。difficile菌株630以剂量依赖性的方式。丁酸盐的存在也增加了C.艰难梭菌孢子形成，毒素产生增加最小。RNA-Seq分析验证了我们的实验结果，证明了孢子形成相关基因的表达增加，以及代谢和调控基因的变化，如假定的碳饥饿蛋白CstA。总的来说，这些数据表明丁酸盐可以诱导替代C。艰难的生存途径，改变其生长能力和毒力，使其在肠道环境中持续存在。几项研究表明，丁酸盐可以调节肠道感染，例如减少由医疗保健相关的艰难梭菌引起的炎症。虽然动物模型和人类研究的研究都将高水平的丁酸盐与降低的C。艰难梭菌负荷，丁酸盐对C. difficile仍然不清楚。我们的研究表明，丁酸直接影响C。通过增加其孢子形成和改变其代谢，可能使用丁酸盐作为生物标志物，以改变在不断变化的肠道环境中的生存策略。这些数据指出了其他治疗方法来对抗C。以丁酸盐导向的方式进行艰难梭菌。
Short-chain fatty acids (SCFAs) are products of bacterial fermentation that help maintain important gut functions such as maintenance of the intestinal barrier, cell signaling, and immune homeostasis. The main SCFAs acetate, propionate, and butyrate have demonstrated beneficial effects for the host, including its importance in alleviating infections caused by pathogens such as Clostridioides difficile. Despite the potential role of SCFAs in mitigating C. difficile infection, their direct effect on C. difficile remains unclear. Through a set of in vitro experiments, we investigated how SCFAs influence C. difficile growth, sporulation, and toxin production. Similar to previous studies, we observed that butyrate decreased growth of C. difficile strain 630 in a dose-dependent manner. The presence of butyrate also increased C. difficile sporulation, with minimal increases in toxin production. RNA-Seq analysis validated our experimental results, demonstrating increased expression of sporulation-related genes in conjunction with changes in metabolic and regulatory genes, such as a putative carbon starvation protein, CstA. Collectively, these data suggest that butyrate may induce alternative C. difficile survival pathways, modifying its growth ability and virulence to persist in the gut environment. Several studies suggest that butyrate may modulate gut infections, such as reducing inflammation caused by the healthcare-associated Clostridioides difficile. While studies in both animal models and human studies correlate high levels of butyrate with reduced C. difficile burden, the direct impact of butyrate on C. difficile remains unclear. Our study demonstrates that butyrate directly influences C. difficile by increasing its sporulation and modifying its metabolism, potentially using butyrate as a biomarker to shift survival strategies in a changing gut environment. These data point to additional therapeutic approaches to combat C. difficile in a butyrate-directed manner.
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影响因子：
11.1
作者：
Deleu S;Machiels K;Raes J;Verbeke K;Vermeire S
通讯作者：
Vermeire S
美国梭菌艰难梭菌感染和结果负担的趋势。
DOI：
10.1056/nejmoa1910215
发表时间：
2020-04-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Guh AY;Mu Y;Winston LG;Johnston H;Olson D;Farley MM;Wilson LE;Holzbauer SM;Phipps EC;Dumyati GK;Beldavs ZG;Kainer MA;Karlsson M;Gerding DN;McDonald LC;Emerging Infections Program Clostridioides difficile Infection Working Group
通讯作者：
Emerging Infections Program Clostridioides difficile Infection Working Group
影响因子：
3.1
作者：
Allegretti JR;Marcus J;Storm M;Sitko J;Kennedy K;Gerber GK;Bry L
通讯作者：
Bry L
影响因子：
30.3
作者：
Girinathan BP;DiBenedetto N;Worley JN;Peltier J;Arrieta-Ortiz ML;Immanuel SRC;Lavin R;Delaney ML;Cummins CK;Hoffman M;Luo Y;Gonzalez-Escalona N;Allard M;Onderdonk AB;Gerber GK;Sonenshein AL;Baliga NS;Dupuy B;Bry L
通讯作者：
Bry L
影响因子：
3.1
作者：
Deakin, Laura J.;Clare, Simon;Lawley, Trevor D.
通讯作者：
Lawley, Trevor D.