Fujimoto Kosuke, Kimura Yasumasa, Allegretti Jessica R, Yamamoto Mako, Zhang Yao-Zhong, Katayama Kotoe, Tremmel Georg, Kawaguchi Yunosuke, Shimohigoshi Masaki, Hayashi Tetsuya, Uematsu Miho, Yamaguchi Kiyoshi, Furukawa Yoichi, Akiyama Yutaka, Yamaguchi Rui, Crowe Sheila E, Ernst Peter B, Miyano Satoru, Kiyono Hiroshi, Imoto Seiya, Uematsu Satoshi
Department of Immunology and Genomics, Osaka City University, Graduate School of Medicine, Abeno-ku, Osaka, Japan; Division of Metagenome Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan; Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Division of Systems Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Gastroenterology. 2021 May;160(6):2089-2102.e12. doi: 10.1053/j.gastro.2021.02.013. Epub 2021 Feb 9.
BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI). However, the overall mechanisms underlying FMT success await comprehensive elucidation, and the safety of FMT has recently become a serious concern because of the occurrence of drug-resistant bacteremia transmitted by FMT. We investigated whether functional restoration of the bacteriomes and viromes by FMT could be an indicator of successful FMT.
The human intestinal bacteriomes and viromes from 9 patients with rCDI who had undergone successful FMT and their donors were analyzed. Prophage-based and CRISPR spacer-based host bacteria-phage associations in samples from recipients before and after FMT and in donor samples were examined. The gene functions of intestinal microorganisms affected by FMT were evaluated.
Metagenomic sequencing of both the viromes and bacteriomes revealed that FMT does change the characteristics of intestinal bacteriomes and viromes in recipients after FMT compared with those before FMT. In particular, many Proteobacteria, the fecal abundance of which was high before FMT, were eliminated, and the proportion of Microviridae increased in recipients. Most temperate phages also behaved in parallel with the host bacteria that were altered by FMT. Furthermore, the identification of bacterial and viral gene functions before and after FMT revealed that some distinctive pathways, including fluorobenzoate degradation and secondary bile acid biosynthesis, were significantly represented.
The coordinated action of phages and their host bacteria restored the recipients' intestinal flora. These findings show that the restoration of intestinal microflora functions reflects the success of FMT.
粪便微生物群移植（FMT）是治疗复发性艰难梭菌感染（rCDI）的有效方法。然而，FMT成功的总体机制仍有待全面阐明，并且由于FMT传播耐药菌血症的发生，FMT的安全性最近已成为一个严重问题。我们研究了FMT对细菌群落和病毒群落的功能恢复是否可能是FMT成功的一个指标。
分析了9例接受成功FMT的rCDI患者及其供体的人类肠道细菌群落和病毒群落。检查了FMT前后受体样本以及供体样本中基于前噬菌体和基于CRISPR间隔序列的宿主细菌-噬菌体关联。评估了受FMT影响的肠道微生物的基因功能。
病毒群落和细菌群落的宏基因组测序显示，与FMT前相比，FMT确实改变了受体肠道细菌群落和病毒群落的特征。特别是，许多在FMT前粪便丰度较高的变形菌被清除，受体中微小病毒科的比例增加。大多数温和噬菌体的行为也与受FMT改变的宿主细菌平行。此外，FMT前后细菌和病毒基因功能的鉴定表明，一些独特的途径，包括氟苯甲酸降解和次级胆汁酸生物合成，有显著体现。
噬菌体与其宿主细菌的协同作用恢复了受体的肠道菌群。这些发现表明肠道微生物群功能的恢复反映了FMT的成功。
