Ursodeoxycholic Acid Inhibits Clostridium difficile Spore Germination and Vegetative Growth, and Prevents the Recurrence of Ileal Pouchitis Associated With the Infection.
Ursodeoxycholic Acid Inhibits Clostridium difficile Spore Germination and Vegetative Growth, and Prevents the Recurrence of Ileal Pouchitis Associated With the Infection.
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DOI：
10.1097/mcg.0000000000000427
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发表时间：
2016-09
影响因子：
2.9
通讯作者：
Khoruts A
中科院分区：
文献类型：
--
作者：
Weingarden AR;Chen C;Zhang N;Graiziger CT;Dosa PI;Steer CJ;Shaughnessy MK;Johnson JR;Sadowsky MJ;Khoruts A
试验熊去氧胆酸对艰难梭菌是否有抑制作用，能否用于治疗艰难梭菌相关性回肠袋炎。恢复胆汁次生代谢可能是粪便微生物群移植（FMT）治疗复发性艰难梭菌感染（RCDI）的关键机制。因此，有可能外源性给药抑制胆汁酸可以直接用作非抗生素治疗这种适应症。难治性难治性艰难梭菌相关性眼袋炎患者尤其需要这种治疗方案，其中FMT的疗效可能有限。我们测量了熊去氧胆酸（UDCA）对11株难状梭菌临床分离菌株的萌发和营养生长的抑制能力，这些菌株来自接受FMT治疗的RCDI患者。此外，我们使用口服UDCA治疗一名RCDI包囊炎患者，该患者对多种抗生素治疗和FMT均难治。UDCA对难辨梭菌的萌发和营养生长均有抑制作用。RCDI袋炎患者的粪便UDCA浓度超过了体外抑制艰难梭菌萌发和生长所需的水平。在UDCA开始后，患者保持无感染超过10个月。UDCA可以被认为是难辨梭菌相关性眼袋炎患者的一种治疗选择。需要做进一步的研究来确定这种治疗的最佳剂量和持续时间。此外，胆汁酸衍生物对艰难梭菌的抑制能够达到高的结肠内浓度，可以作为治疗RCDI结肠炎的药物。
Test whether ursodeoxycholic acid is inhibitory to Clostridium difficile and can be used in the treatment of C. difficile associated ileal pouchitis. Restoration of secondary bile metabolism may be the key mechanism for fecal microbiota transplantation (FMT) in treating recurrent C. difficile infections (RCDI). Therefore, it is possible that exogenous administration of inhibitory bile acids may be used directly as non-antibiotic therapeutics for this indication. The need for such a treatment alternative is especially great in patients with refractory C. difficile associated pouchitis, where the efficacy of FMT may be limited. We measured the ability of ursodeoxycholic acid (UDCA) to suppress germination and vegetative growth of 11 clinical isolate strains of C. difficile from patients treated with FMT for RCDI. In addition, we used oral UDCA to treat a patient with RCDI pouchitis that proved refractory to multiple antibiotic treatments and FMT. UDCA was found inhibitory to germination and vegetative growth of all C. difficile strains tested. Fecal concentrations of UDCA from the patient with RCDI pouchitis exceeded levels necessary to inhibit germination and growth of C. difficile in vitro. The patient has remained infection-free for over ten months following initiation of UDCA. UDCA can be considered as a therapeutic option in patients with C. difficile associated pouchitis. Further studies need to be done to define the optimal dose and duration of such treatment. In addition, bile acid derivatives inhibitory to C. difficile that are able to achieve high intracolonic concentrations may be developed as therapeutics for RCDI colitis.