当前艰难梭菌感染(CDI)的治疗策略,包括口服万古霉素,甲硝唑和粪便微生物移植,疗效有限,治疗失败可能发生在多达三分之一的病例中。最近的研究已经报道,较低浓度的25-羟基维生素D与CDI严重程度和复发有关。然而,目前尚无关于CDI患者服用维生素D后微生物群组成的研究.因此,我们的研究旨在比较两组之间的微生物群组成,通过使用16SrRNA微生物谱分析,包括8名补充维生素D的CDI阳性患者和10名未补充维生素D的CDI阳性患者。
这项前瞻性随机对照研究纳入了20名受试者。一名受试者因出院后与监护人缺乏联系而退学,一名受试者因撤回同意而退学。因此,将18例CDI和维生素D不足(维生素D水平<17ng/mL)的患者分为两组:补充维生素D的CDI(n=8)和不补充维生素D的CDI(对照组:n=10)。维生素D不足的受试者随机接受200,000IU肌注胆钙化醇,而对照组患者仅口服万古霉素。在施用万古霉素之前和治疗后八周获得粪便样品两次;使用EzBioCloud进行V3-V416SrRNA宏基因组测序。
恢复状态的肠道微生物群的α多样性明显高于CDI状态。细菌相对丰度分析显示显著较低的变形杆菌和较高的落叶松科细菌,Ruminocycaceae,Akkermansiaceae,和恢复状态的双歧杆菌。在八周后比较对照组和维生素D治疗组时,alpha多样性的增加,丰富的落叶松科,和反刍动物科在两组中表现出相同的趋势。在维生素D组中观察到双歧杆菌科和Christensenellaceae的显着增加;维生素D治疗组的变形杆菌丰度在八周后明显低于对照组。
我们的研究证实,有益菌如双歧杆菌的丰度增加,服用高剂量的胆钙化醇后,在恢复过程中,Christensenellaceae尤为明显。这些发现表明,维生素D的给药可能对CDI患者有用,需要更大样本量的进一步研究。
Current therapeutic strategies for Clostridioides difficile infections (CDI), including oral vancomycin, metronidazole and fecal microbial transplantation, have limited efficacy and treatment failure may occur in as many as one- third of cases. Recent studies have reported that lower concentrations of 25-hydroxyvitamin D are associated with CDI severity and recurrence. However, there have been no studies on microbiota composition after the administration of vitamin D in patients with CDI. Therefore, our study aimed to compare the microbiota composition between the two groups, including eight CDI-positive patients with vitamin D supplementation and ten CDI-positive patients without vitamin D supplementation by using 16S rRNA microbial profiling.
Twenty subjects were enrolled in this prospective randomized controlled study. One subject dropped out due to lack of contact with the guardian after discharge and one subject dropped out due to withdrawal of consent. Thus, 18 patients with CDI and vitamin D insufficiency (vitamin D level < 17 ng/mL) were divided into two groups: CDI with vitamin D supplementation (n = 8) and CDI without vitamin D supplementation (control: n = 10). Subjects with vitamin D insufficiency were randomized to receive 200,000 IU intramuscular cholecalciferol whereas patients in the control group received only oral vancomycin. Stool samples were obtained twice before vancomycin was administered and eight weeks after treatment; the V3-V4 16S rRNA metagenomic sequencing was performed using EzBioCloud.
The alpha diversity of the gut microbiota in the recovery state was significantly higher than that in the CDI state. Analysis of bacterial relative abundance showed significantly lower Proteobacteria and higher Lachnospiraceae, Ruminococcaceae, Akkermansiaceae, and
Bifidobacteriaceae in the recovery state. When comparing the control and vitamin D treatment groups after eight weeks, increase in alpha diversity and, abundance of Lachnospiraceae, and Ruminococcaceae exhibited the same trend in both groups. A significant increase in
Bifidobacteriaceae and Christensenellaceae was observed in the vitamin D group; Proteobacteria abundance was significantly lower in the vitamin D treatment group after eight weeks than that in the control group.
Our study confirmed that the increase in the abundance of beneficial bacteria such as
Bifidobacteriaceae, and Christensenellaceae were prominently evident during recovery after administration of a high dose of cholecalciferol. These findings indicate that vitamin D administration may be useful in patients with CDI, and further studies with larger sample sizes are required.