University of Glasgow, College of Medical, Veterinary and Life Sciences, School of Molecular Biosciences, Davidson Bld, Glasgow, U.K.
Department of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska Institutet, Stockholm, Sweden.
Clin Sci (Lond). 2023 Oct 31;137(20):1563-1575. doi: 10.1042/CS20230779.
Dialysis and kidney transplantation (Ktx) mitigate some of the physiological deficits in chronic kidney disease (CKD), but it remains to be determined if these mitigate microbial dysbiosis and the production of inflammatory microbial metabolites, which contribute significantly to the uraemic phenotype. We have investigated bacterial DNA signatures present in the circulation of CKD patients and those receiving a KTx. Our data are consistent with increasing dysbiosis as CKD progresses, with an accompanying increase in trimethylamine (TMA) producing pathobionts Pseudomonas and Bacillus. Notably, KTx patients displayed a significantly different microbiota compared with CKD5 patients, which surprisingly included further increase in TMA producing Bacillus and loss of salutogenic Lactobacilli. Only two genera (Viellonella and Saccharimonidales) showed significant differences in abundance following KTx that may reflect a reciprocal relationship between TMA producers and utilisers, which supersedes restoration of a normative microbiome. Our metadata analysis confirmed that TMA N-oxide (TMAO) along with one carbon metabolism had significant impact upon both inflammatory burden and the composition of the microbiome. This indicates that these metabolites are key to shaping the uraemic microbiome and might be exploited in the development of dietary intervention strategies to both mitigate the physiological deficits in CKD and enable the restoration of a more salutogenic microbiome.
透析和肾移植（Ktx）减轻了慢性肾脏病（CKD）的一些生理缺陷，但仍需确定这些方法是否减轻了微生物失调和炎症性微生物代谢产物的产生，这些产物对尿毒症表型有重要贡献。我们研究了存在于 CKD 患者和接受 Ktx 的患者循环中的细菌 DNA 特征。我们的数据与 CKD 进展时的失调增加一致，伴随着产三甲胺（TMA）的机会致病菌假单胞菌和芽孢杆菌的增加。值得注意的是，与 CKD5 患者相比，Ktx 患者的微生物群明显不同，令人惊讶的是，TMA 产生的芽孢杆菌进一步增加，而有益的乳酸杆菌减少。只有两个属（Viellonella 和 Saccharimonidales）在 Ktx 后表现出显著的丰度差异，这可能反映了 TMA 生产者和利用者之间的相互关系，这种关系取代了规范微生物组的恢复。我们的元数据分析证实，三甲胺 N-氧化物（TMAO）和一碳代谢对炎症负担和微生物组的组成都有显著影响。这表明这些代谢物是塑造尿毒症微生物组的关键，可能会被用于开发饮食干预策略，以减轻 CKD 的生理缺陷，并恢复更有益的微生物组。
