Department of Genetics, Hugh Kaul Precision Medicine Institute, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Department of Cell, Developmental and Integrative Biology, Hugh Kaul Precision Medicine Institute, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
PLoS One. 2022 Sep 15;17(9):e0274633. doi: 10.1371/journal.pone.0274633. eCollection 2022.
Fecal microbial transplantation (FMT) has been used with the therapeutic intent to change the functions of the gut microbial community in metabolism and host immunity. For most of these therapies, the recipients are not given antibiotics to eliminate the microbial community prior to transplant with donor fecal microbes resulting in the initial gut microbial community following FMT consisting of a consortium of donor and recipient microbes. The detailed analysis of the fecal samples from these FMT over time provides a unique opportunity to study the changes in the gut microbial strain community that occurs following the introduction of new microbial strains (donor) into an established community (recipient).
In this study, we have metagenomic data set consisting of 5 FMT that contained donor, recipient and recipient post FMT taken multiple times for periods up to 535 days after the FMT. We used two established strain tracking methods, Window-based Single Nucleotide Variant (SNV) Similarity (WSS) and StrainPhlAn, to determine the presence of donor and recipient microbial strains following FMT. To assess recombination between donor and recipient strains of Bacteroides vulgatus post FMT, we used BLAST+ to analyze the data sets for Bacteroidales-specific antimicrobial proteins (BSAP-3) that have known functions to restrict species specific replication.
We found that Alistipes onderdonkii, Alistipes shahii, Alistipes putredinis, and Parabacteroides merdae, all had patterns post FMT consisting of either dominant donor or recipient microbial strains in the feces. In contrast, the analysis of Bacteroides spp. in five FMT pairs revealed inter-individual oscillation over time with the appearance of either donor or recipient fecal strain dominance. In some instances, B. vulgatus and B. uniformis were also identified after FMT that were not related to either the donor or recipient. Finally, in one of the FMT, we identified a distinct B. vulgatus strain post-FMT that matched the pre-FMT strain but was BSAP-3 positive, suggesting a possible recombination event between the donor and recipient strains.
The complex oscillating patterns of the appearance of fecal dominant donor, recipient or unrelated strains following extended times post FMT provide new insights into the dynamics of the microbial community interactions with the recipients following FMT. The result from our analysis has implications for the use of FMT to predictably change the biological functions of the gut community in metabolism and host immunity.
粪便微生物移植（FMT）已被用于改变肠道微生物群落的代谢和宿主免疫功能的治疗目的。对于这些治疗方法中的大多数，在移植供体粪便微生物之前，受者没有给予抗生素来消除微生物群落，导致 FMT 后最初的肠道微生物群落由供体和受者微生物的联合体组成。随着时间的推移，对这些 FMT 粪便样本的详细分析提供了一个独特的机会，可以研究在将新的微生物菌株（供体）引入已建立的微生物群落（受体）后，肠道微生物菌株群落的变化。
在这项研究中，我们有一个包含 5 个 FMT 的宏基因组数据集，其中包含供体、受体和受体在 FMT 后最多 535 天内多次采集的粪便样本。我们使用了两种已建立的菌株跟踪方法，基于窗口的单核苷酸变异（SNV）相似性（WSS）和 StrainPhlAn，来确定 FMT 后供体和受体微生物菌株的存在。为了评估 FMT 后 Bacteroides vulgatus 供体和受体菌株之间的重组，我们使用 BLAST+ 分析了具有限制特定物种复制功能的 Bacteroidales 特异性抗菌蛋白（BSAP-3）的数据。
我们发现，Alistipes onderdonkii、Alistipes shahii、Alistipes putredinis 和 Parabacteroides merdae 在 FMT 后都有模式，粪便中要么是主要的供体微生物菌株，要么是主要的受体微生物菌株。相比之下，对五个 FMT 对的 Bacteroides spp.分析显示，随着时间的推移，个体之间出现供体或受体粪便菌株优势的波动。在某些情况下，在 FMT 后也鉴定出与供体或受体无关的 B. vulgatus 和 B. uniformis。最后，在一个 FMT 中，我们鉴定出 FMT 后出现的一种独特的 B. vulgatus 菌株与 FMT 前的菌株匹配，但 BSAP-3 阳性，表明供体和受体菌株之间可能发生了重组事件。
在 FMT 后长时间内，粪便中主要的供体、受体或无关菌株的出现呈现出复杂的波动模式，为 FMT 后微生物群落与受者相互作用的动态提供了新的见解。我们分析的结果对使用 FMT 来可预测地改变肠道菌群在代谢和宿主免疫方面的生物学功能具有重要意义。
