Genetics Program, Department of Biological Sciences, College of Science, North Carolina State University, Raleigh, North Carolina, USA.
Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
mSphere. 2024 Oct 29;9(10):e0070624. doi: 10.1128/msphere.00706-24. Epub 2024 Oct 8.
Recurrent infection (rCDI) is an urgent public health threat, for which the last resort and lifesaving treatment is a fecal microbiota transplant (FMT). However, the exact mechanisms that mediate a successful FMT are not well-understood. Here, we use longitudinal stool samples collected from patients undergoing FMT to evaluate intra-individual changes in the microbiome, metabolome, and lipidome after successful FMTs relative to their baselines pre-FMT. We show changes in the abundance of many lipids, specifically a decrease in acylcarnitines post-FMT, and a shift from conjugated bile acids pre-FMT to deconjugated secondary bile acids post-FMT. These changes correlate with a decrease in Enterobacteriaceae, which encode carnitine metabolism genes, and an increase in Lachnospiraceae, which encode bile acid altering genes such as bile salt hydrolases (BSHs) and the bile acid-inducible () operon, post-FMT. We also show changes in gut microbe-encoded amino acid biosynthesis genes, of which Enterobacteriaceae was the primary contributor to amino acids is auxotrophic for. Liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) revealed a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here, we define the structural and functional changes associated with a successful FMT and generate hypotheses that require further experimental validation. This information is meant to help guide the development of new microbiota-focused therapeutics to treat rCDI.IMPORTANCERecurrent infection is an urgent public health threat, for which the last resort and lifesaving treatment is a fecal microbiota transplant. However, the exact mechanisms that mediate a successful FMT are not well-understood. Here, we show changes in the abundance of many lipids, specifically acylcarnitines and bile acids, in response to FMT. These changes correlate with Enterobacteriaceae pre-FMT, which encodes carnitine metabolism genes, and Lachnospiraceae post-FMT, which encodes bile salt hydrolases and genes. There was also a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here, we define the structural and functional changes associated with a successful FMT, which we hope will help aid in the development of new microbiota-focused therapeutics to treat rCDI.
复发性感染 (rCDI) 是一个紧迫的公共卫生威胁，对于这种威胁，最后的治疗方法和救生治疗是粪便微生物群移植 (FMT)。然而，介导成功 FMT 的确切机制尚不清楚。在这里，我们使用从接受 FMT 的患者中纵向收集的粪便样本，评估相对于基线 (pre-FMT)，成功 FMT 后微生物组、代谢组和脂质组的个体内变化。我们显示出许多脂质的丰度发生变化，特别是 FMT 后酰基辅酶 A 的减少，以及 FMT 前共轭胆汁酸向 FMT 后去共轭次级胆汁酸的转变。这些变化与肠杆菌科的减少相关，肠杆菌科编码肉碱代谢基因，而厚壁菌门的增加与 FMT 后胆汁酸改变基因（如胆汁盐水解酶 (BSHs) 和胆汁酸诱导 () 操纵子）相关，FMT 后胆汁酸改变基因（如胆汁盐水解酶 (BSHs) 和胆汁酸诱导 () 操纵子）相关。我们还显示了肠道微生物编码的氨基酸生物合成基因的变化，其中肠杆菌科是氨基酸的主要贡献者。液相色谱、离子迁移谱和质谱 (LC-IMS-MS) 显示 FMT 前初级胆汁酸的微生物共轭向 FMT 后次级胆汁酸的转变。在这里，我们定义了与成功 FMT 相关的结构和功能变化，并提出了需要进一步实验验证的假设。这些信息旨在帮助指导新的以微生物组为重点的治疗方法的开发，以治疗 rCDI。
复发性感染是一个紧迫的公共卫生威胁，对于这种威胁，最后的治疗方法和救生治疗是粪便微生物群移植 (FMT)。然而，介导成功 FMT 的确切机制尚不清楚。在这里，我们显示了 FMT 后许多脂质（特别是酰基辅酶 A 和胆汁酸）的丰度发生变化。这些变化与 FMT 前肠杆菌科相关，肠杆菌科编码肉碱代谢基因，FMT 后厚壁菌门相关，厚壁菌门编码胆汁盐水解酶和 基因。FMT 前初级胆汁酸的微生物共轭也向 FMT 后次级胆汁酸转变。在这里，我们定义了与成功 FMT 相关的结构和功能变化，我们希望这将有助于开发新的以微生物组为重点的治疗方法来治疗 rCDI。
