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mSphere:抗生素如何杀灭修饰胆汁酸的细菌进而促进芽孢杆菌的感染

  1. 感染
  2. 抗生素
  3. 细菌
  4. 胆汁酸
  5. 艰难梭状芽胞杆菌

来源:生物谷 2016-01-11 16:13

近日,来自北卡罗来纳州立大学等机构的研究人员通过研究发现,可以被大肠中生存的细菌改变的胆汁酸或可抑制艰难梭状芽胞杆菌(C. diff)的生长,这种细菌是一种可以引发机体疼痛甚至死亡的有害细菌,相关研究刊登于国际杂志mSphere上,本文研究为后期科学家们制定新型策略,来避免使用抗生素杀灭改变胆汁酸的微生物进而促进艰难梭状芽胞杆菌引发感染提供了新的希望。

图片来源:medicalxpress.com

2016年1月11日 讯 /生物谷BIOON/ --近日,来自北卡罗来纳州立大学等机构的研究人员通过研究发现,可以被大肠中生存的细菌改变的胆汁酸或可抑制艰难梭状芽胞杆菌(C. diff)的生长,这种细菌是一种可以引发机体疼痛甚至死亡的有害细菌,相关研究刊登于国际杂志mSphere上,本文研究为后期科学家们制定新型策略,来避免使用抗生素杀灭改变胆汁酸的微生物进而促进艰难梭状芽胞杆菌引发感染提供了新的希望。

艰难梭状芽胞杆菌通常以休眠状态存在于环境中,为了在肠道中定植,细菌孢子就需要萌芽并且变成生长中的细菌进而产生毒素来损伤大肠组织;研究人员已经知道特殊抗生素的使用会引发机体发生高风险的细菌感染,而本文中研究者想通过研究阐明艰难梭状芽胞杆菌的芽孢如何同微生物群落相互作用。

研究者Casey Theriot说道,我们知道在一个健康的肠道环境中,艰难梭状芽胞杆菌的生长会被抑制,但我们想通过研究阐明隐藏在这种抑制效应背后的机制;胆汁酸源自机体脂肪消化和吸收后的胆固醇和酸而产生,胆汁酸可以控制脂蛋白、葡萄糖、药物及机体的能量代谢,初级胆汁酸可以在肝脏中产生,而且通过肠道系统,在大肠中细菌会将这些胆汁酸转化成为次级胆汁酸,而研究者发现大量次级胆汁酸会对艰难梭状芽胞杆菌的生长带来一致性效应。

随后研究者观察了小鼠在多种不同抗生素治疗前后肠道内容物的差别,他们在小鼠治疗前后鉴别出了26种不同的初级胆汁酸和次级胆汁酸,并且确定了他们的浓度,随后研究者将艰难梭状芽胞杆菌的芽孢加入到这些内容物中,目的在于寻找这些细菌如何在现实的肠道环境中萌芽并且生长。更有意思的是,研究人员还发现,小肠中的初级胆汁酸会促进细菌的芽孢萌发,并且开始生长,而这同是否进行抗生素治疗并无关联。

当细菌芽孢到达大肠时,正常的肠道细菌就会产生刺激胆汁酸,于是研究人员就发现,这些次级胆汁酸会阻断难梭状芽胞杆菌的生长;而当这些细菌在抗生素疗法后并不存在时这些芽孢杆菌就会很快生长;本文研究对于理解肠道微生物通过肠道来调节胆汁酸的机制提供了新的思路,研究人员希望后期可以开发出难梭状芽胞杆菌的新型疗法,以及治疗代谢相关疾病,比如肥胖和糖尿病的新型个体化疗法。(生物谷Bioon.com)

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Antibiotic-Induced Alterations of the Gut Microbiota Alter Secondary Bile Acid Production and Allow for Clostridium difficile Spore Germination and Outgrowth in the Large Intestine

Casey M. Theriot[a][b], Alison A. Bowman[b], Vincent B. Young[b][c]

It is hypothesized that the depletion of microbial members responsible for converting primary bile acids into secondary bile acids reduces resistance to Clostridium difficile colonization. To date, inhibition of C. difficile growth by secondary bile acids has only been shown in vitro. Using targeted bile acid metabolomics, we sought to define the physiologically relevant concentrations of primary and secondary bile acids present in the murine small and large intestinal tracts and how these impact C. difficile dynamics. We treated mice with a variety of antibiotics to create distinct microbial and metabolic (bile acid) environments and directly tested their ability to support or inhibit C. difficile spore germination and outgrowth ex vivo. Susceptibility to C. difficile in the large intestine was observed only after specific broad-spectrum antibiotic treatment (cefoperazone, clindamycin, and vancomycin) and was accompanied by a significant loss of secondary bile acids (deoxycholate, lithocholate, ursodeoxycholate, hyodeoxycholate, and ω-muricholate). These changes were correlated to the loss of specific microbiota community members, the Lachnospiraceae and Ruminococcaceae families. Additionally, physiological concentrations of secondary bile acids present during C. difficile resistance were able to inhibit spore germination and outgrowth in vitro. Interestingly, we observed that C. difficile spore germination and outgrowth were supported constantly in murine small intestinal content regardless of antibiotic perturbation, suggesting that targeting growth of C. difficile will prove most important for future therapeutics and that antibiotic-related changes are organ specific. Understanding how the gut microbiota regulates bile acids throughout the intestine will aid the development of future therapies for C. difficile infection and other metabolically relevant disorders such as obesity and diabetes.

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