Department of Biomedical Data Intelligence, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Nephrol Dial Transplant. 2021 Aug 27;36(9):1675-1684. doi: 10.1093/ndt/gfaa122.
The relationship between chronic kidney disease (CKD) and the gut microbiome, which interact through chronic inflammation, uraemic toxin production and immune response regulation, has gained interest in the development of CKD therapies. However, reports using shotgun metagenomic analysis of the gut microbiome are scarce, especially for early CKD. Here we characterized gut microbiome differences between non-CKD participants and ones with early CKD using metagenomic sequencing.
In total, 74 non-CKD participants and 37 participants with early CKD were included based on propensity score matching, controlling for various factors including dietary intake. Stool samples were collected from participants and subjected to shotgun sequencing. Bacterial and pathway abundances were profiled at the species level with MetaPhlAn2 and HUMAnN2, respectively, and overall microbiome differences were determined using Bray-Curtis dissimilarities. Diabetic and non-diabetic populations were analysed separately.
For diabetic and non-diabetic participants, the mean estimated glomerular filtration rates of the CKD group were 53.71 [standard deviation (SD) 3.87] and 53.72 (SD 4.44), whereas those of the non-CKD group were 72.63 (SD 7.72) and 76.10 (SD 9.84), respectively. Alpha and beta diversities were not significantly different between groups. Based on taxonomic analysis, butyrate-producing species Roseburia inulinivorans, Ruminococcus torques and Ruminococcus lactaris were more abundant in the non-CKD group, whereas Bacteroides caccae and Bacteroides coprocora were more abundant in the non-diabetic CKD group.
Although gut microbiome changes in individuals with early CKD were subtle, the results suggest that changes related to producing short-chain fatty acids can already be observed in early CKD.
慢性肾脏病（CKD）与肠道微生物组之间的关系通过慢性炎症、尿毒素产生和免疫反应调节相互作用，引起了人们对 CKD 治疗方法的关注。然而，利用肠道微生物组的鸟枪法宏基因组分析进行相关研究的报道很少，尤其是在早期 CKD 方面。本研究通过宏基因组测序对非 CKD 参与者和早期 CKD 参与者的肠道微生物组进行了特征描述。
根据倾向评分匹配，共纳入了 74 名非 CKD 参与者和 37 名早期 CKD 参与者，控制了包括饮食摄入在内的各种因素。从参与者中收集粪便样本，并进行鸟枪法测序。使用 MetaPhlAn2 和 HUMAnN2 分别对细菌和途径丰度进行物种水平的分析，并使用 Bray-Curtis 不相似性来确定整体微生物组的差异。分别对糖尿病和非糖尿病人群进行了分析。
对于糖尿病和非糖尿病参与者，CKD 组的平均估计肾小球滤过率（eGFR）分别为 53.71[标准差（SD）3.87]和 53.72（SD 4.44），而非 CKD 组分别为 72.63（SD 7.72）和 76.10（SD 9.84）。两组间的 alpha 和 beta 多样性没有显著差异。基于分类分析，非 CKD 组中丁酸盐产生菌罗斯伯里氏菌属（Roseburia）、梭菌属（Ruminococcus）torques 和 Ruminococcus lactaris 更为丰富，而非糖尿病 CKD 组中拟杆菌属（Bacteroides） caccae 和 Bacteroides coprocora 更为丰富。
尽管早期 CKD 患者肠道微生物组的变化很细微，但结果表明，早期 CKD 患者已经可以观察到与产生短链脂肪酸相关的变化。
