Research Department, Sidra Medicine, OPC, P.O. Box 26999, Doha, Qatar.
Pediatric Nephrology and Hypertension, Sidra Medicine, HB. 7A. 106A, P.O. Box 26999, Doha, Qatar; Weill Cornell College of Medicine-Qatar, Ar-Rayyan, Doha, Qatar; Medical University of South Carolina, Charleston, SC, USA.
Biomed Pharmacother. 2021 Aug;140:111736. doi: 10.1016/j.biopha.2021.111736. Epub 2021 May 23.
Children with Type 1 diabetes mellitus (T1DM) have an elevated risk of abnormal blood pressure (BP) measurements and patterns. Both hypertension and T1DM are well-known risk factors for cardiovascular disease and kidney failure. The human microbiome has been linked to both diabetes and hypertension, but the relationship between the gut microbiome and BP in children with T1DM is not well-understood. In this cross-sectional study, we examined the relationship between resting office BP and gut microbiota composition, diversity, and richness in children with T1DM and healthy controls. We recruited 29 pediatric subjects and divided them into three groups: healthy controls (HC, n = 5), T1DM with normal BP (T1DM-Normo, n = 17), and T1DM with elevated BP (T1DM-HBP, n = 7). We measured the BP, dietary and clinical parameters for each subject. We collected fecal samples to perform the 16s rDNA sequencing and to measure the short-chain fatty acids (SCFAs) level. The microbiome downstream analysis included the relative abundance of microbiota, alpha and beta diversity, microbial markers using Linear Discriminant effect size analysis (LEfSe), potential gut microbial metabolic pathways using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) and metabolic pathways validation using Statistical Inference of Associations between Microbial Communities And host phenotype (SIAMCAT) machine learning toolbox. Our study results showed that T1DM-HBP group had distinct gut microbial composition (at multiple taxonomic levels) and reduced diversity (richness and abundance) compared with T1DM-Normo and HC groups. Children with T1DM-HBP showed a significant reduction of Bifidobacterium levels (especially B. adolescentis, B. bifidum, and B. longum) compared to the T1DM-Normo group. We also observed unique gut-microbial metabolic pathways, such as elevated lipopolysaccharide synthesis and glutathione metabolism in children with T1DM-HBP compared to T1DM-Normo children. We can conclude that the reduction in the abundance of genus Bifidobacterium could play a significant role in elevating the BP in pediatric T1DM subjects. More studies are needed to corroborate our findings and further explore the potential contributing mechanisms we describe.
患有 1 型糖尿病（T1DM）的儿童血压（BP）测量值和模式异常的风险较高。高血压和 T1DM 都是心血管疾病和肾衰竭的已知危险因素。人类微生物组与糖尿病和高血压都有关，但 T1DM 儿童肠道微生物组与 BP 的关系尚未得到充分了解。在这项横断面研究中，我们研究了 T1DM 儿童和健康对照组中静息办公室 BP 与肠道微生物群落组成、多样性和丰富度之间的关系。我们招募了 29 名儿科患者，并将他们分为三组：健康对照组（HC，n=5）、T1DM 血压正常组（T1DM-Normo，n=17）和 T1DM 血压升高组（T1DM-HBP，n=7）。我们测量了每位患者的 BP、饮食和临床参数。我们收集粪便样本进行 16s rDNA 测序和短链脂肪酸（SCFA）水平测量。微生物组下游分析包括微生物相对丰度、alpha 和 beta 多样性、使用线性判别效应大小分析（LEfSe）的微生物标志物、使用未观察状态群落重建的群落系统发育分析（PICRUSt）的潜在肠道微生物代谢途径以及使用微生物群落和宿主表型之间关联的统计推断（SIAMCAT）机器学习工具箱验证代谢途径。我们的研究结果表明，与 T1DM-Normo 和 HC 组相比，T1DM-HBP 组的肠道微生物组成（在多个分类水平上）存在明显差异，多样性（丰富度和丰度）降低。与 T1DM-Normo 组相比，T1DM-HBP 组双歧杆菌水平显著降低（特别是双歧杆菌、双歧杆菌和长双歧杆菌）。与 T1DM-Normo 儿童相比，我们还观察到 T1DM-HBP 儿童独特的肠道微生物代谢途径，如脂多糖合成和谷胱甘肽代谢升高。我们可以得出结论，双歧杆菌属丰度的降低可能在儿科 T1DM 患者的 BP 升高中发挥重要作用。需要进一步的研究来证实我们的发现，并进一步探索我们描述的潜在致病机制。
