Department of Genetics, Hugh Kaul Precision Medicine Institute, University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Cell, Developmental and Integrative Biology, Hugh Kaul Precision Medicine Institute, University of Alabama at Birmingham, Birmingham, AL, USA.
Sci Rep. 2023 Aug 29;13(1):14112. doi: 10.1038/s41598-023-41128-y.
Due to suppressive antibiotics, patients with recurrent Clostridium difficile have gut microbial communities that are devoid of most commensal microbes. Studies have shown that most of the failures using fecal microbe transplantation (FMT) for recurrent C. difficile occur during the first 4 weeks following transplantation. To identify features of donor Bacteroides vulgatus that lead to early colonization, we used two data sets that collected fecal samples from recipients at early times points post FMT. The first analysis used the shotgun metagenomic DNA sequencing data set from Aggarwala et al. consisting of 7 FMT donors and 13 patients with recurrent C. difficile with fecal samples taken as early as 24 h post FMT. We identified 2 FMT donors in which colonization of recipients by donor B. vulgatus was detected as early as 24 h post FMT. We examined a second data set from Hourigan et al. that collected fecal samples from C. difficile infected children and identified 1 of 3 FMT that also had early colonization of the donor B. vulgatus. We found 19 genes out of 4911 encoding proteins were unique to the 3 donors that had early colonization. A gene encoding a putative chitobiase was identified that was in a gene complex that had been previously identified to enhance colonization in mice. A gene encoding a unique fimbrillin (i.e., pili) family protein and 17 genes encoding hypothetical proteins were also specific for early colonizing donors. Most of the genes encoding hypothetical proteins had neighboring genes that encoded proteins involved in mobilization or transposition. Finally, analysis of 42 paired fecal samples from the human microbiome project (HMP) found no individuals had all 19 genes while 2 individuals had none of the 19 genes. Based on the results from our study, consideration should be given to the screening of FMT donors for these B. vulgatus genes found to enhance early colonization that would be of benefit to promote colonization following FMT.
由于使用了抑制性抗生素,复发性艰难梭菌患者的肠道微生物群落中几乎没有大多数共生微生物。研究表明,使用粪便微生物移植(FMT)治疗复发性艰难梭菌的大多数失败都发生在移植后 4 周内。为了确定导致早期定植的供体脆弱拟杆菌的特征,我们使用了两个数据集,这些数据集从 FMT 后早期时间点收集了受者的粪便样本。第一项分析使用了 Aggarwala 等人的 shotgun 宏基因组 DNA 测序数据集,该数据集由 7 名 FMT 供体和 13 名复发性艰难梭菌患者组成,粪便样本最早可在 FMT 后 24 小时采集。我们在 24 小时后 FMT 时就检测到供体脆弱拟杆菌定植于受者的 2 名供体。我们检查了来自 Hourigan 等人的第二个数据集,该数据集从感染艰难梭菌的儿童中收集了粪便样本,并鉴定出 3 名 FMT 中的 1 名也有供体脆弱拟杆菌的早期定植。我们在 4911 个编码蛋白的基因中发现了 19 个基因是 3 名具有早期定植的供体所特有的。鉴定出一个编码假定的壳二糖酶的基因,该基因位于先前已被鉴定为增强小鼠定植的基因复合物中。一个独特的 fimbrillin(即菌毛)家族蛋白和 17 个编码假定蛋白的基因也专门针对早期定植的供体。编码假定蛋白的大多数基因都有编码参与移动或转位的蛋白的相邻基因。最后,对人类微生物组计划(HMP)的 42 对粪便样本进行分析发现,没有一个人拥有所有 19 个基因,而有两个人没有一个人拥有所有 19 个基因。基于我们研究的结果,应该考虑对 FMT 供体进行这些脆弱拟杆菌基因的筛选,这些基因被发现可以增强早期定植,这将有助于促进 FMT 后的定植。