目的 分析6~9岁儿童肠道菌群的构成与血压之间的关系,为儿童高血压的预防与治疗提供新思路。方法 2015年12月—2017年3月在广州招募411名6~9岁儿童,使用16S rRNA基因高通量测序测定肠道菌群,分析Alpha多样性和Beta多样性。利用MUVR算法,通过重复交叉验证分析筛选出与血压相关的OTUs。运用Spearman相关及多重线性回归分析探索儿童肠道菌群构成与血压之间的关系。 结果 血压正常儿童与血压异常儿童肠道菌群的Beta多样性差异有统计学意义(R2加权=0.015,P加权=0.01;R2非加权=0.027,P非加权=0.001)。经校正多个协变量和错误发现率(FDR)校正的多重线性回归分析结果显示,儿童血压水平随OTU_3(布劳特氏菌属)、OTU_131(无害梭菌属)、OTU_1776(布劳特氏菌属)、OTU_2159(普雷沃式菌属)和OTU_91(短双歧杆菌种)的丰度增加而下降(β:-0.18~-0.14,PFDR<0.05);相反,儿童血压随OTU_108(萨特氏菌属)、OTU_1(普拉梭菌种)、OTU_8(罗氏菌属)、OTU_48(蓝绿藻菌属)、OTU_81(粪球菌属)、OTU_401(毛螺菌科)、OTU_1284(毛螺菌科)和OTU_2793(毛螺菌科)的丰度增加而升高(β: 0.14~0.21,PFDR<0.05)。而肠道菌群对收缩压和舒张压的影响可能是通过体质量指数(BMI)的增加来介导的。 结论 儿童血压水平与其肠道菌群的构成有关,BMI在二者关系中起到中介作用。建议调节布劳特氏菌属和萨特氏菌属等菌群来控制儿童高血压,同时加强BMI的健康管理。
Abstract
Objective To analyze the association between the composition of gut microbiota and blood pressure in children aged 6 - 9 years, in order to provide new ideas for childhood hypertension prevention and treatment. Methods A total of 411 children aged 6 - 9 years were recruited in Guangzhou from December 2015 to March 2017. The gut microbiota was characterized by 16S ribosomal RNA amplicon sequencing. The multivariate Methods with unbiased variable selection in R (MUVR) were performed to identify the significant OTUs. Spearman correlation as well as multiple linear regression were used to explore the relationship between gut microbiota and blood pressure in children. Results Significant difference in β diversity index was observed between children with normal blood pressure and those with abnormal blood pressure (R2weighted=0.015,Pweighted=0.01;R2unweighted=0.027,Punweighted=0.001). After adjustment for covariates and controlling the false discovery rate (FDR), multiple linear regression analysis showed that blood pressure level in children decreased with the increasing abundance of OTU_3 (genus Blautia), OTU_131 (genus [Clostridium]_innocuum_group), OTU_1776 (genus Blautia), OTU_2159 (genus Prevotella) and OTU_91 (species Bifidobacterium_breve) (β:-0.18 --0.14; PFDR<0.05. In contrast, blood pressure in children increased with theincreasing abundance of OTU_108(genus Sutterella), OTU_1(species Faecalibacterium_prausnitzii)、OTU_8(genus Roseburia), OTU_48 (genus Lachnoclostridium), OTU_81 (genus Coprococcus), OTU_401 (family Lachnospiraceae), OTU_1284 (family Lachnospiraceae) and OTU_2793 (family Lachnospiraceae)(β: 0.14 - 0.21; PFDR<0.05. The influence of gut microbiota on systolic pressure and diastolic pressure may be mediated by the increase of body mass index (BMI). Conclusions Pediatric blood pressure level is associated with the composition of gut microbiota, while BMI partially plays a mediating role in the relationship. It is recommended to modulate the abundance of microbiota as genus Blautia, Sutterella and so on to prevent hypertension in children.
关键词
肠道菌群 /
血压 /
儿童
Key words
microbiota /
blood pressure /
children
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参考文献
[1] Verdecchia P, Reboldi G, Angeli F. The 2020 international society of hypertension global hypertension practice guidelines - key messages and clinical considerations[J]. Eur J Intern Med, 2020, 82: 1-6.
[2] 中国心血管健康与疾病报告编写组.《中国心血管健康与疾病报告2020》概述[J].中国心血管病研究, 2021, 19(7): 582-590.
The Writing Committee of the Report on Cardiovascular Health and Diseases in China. Key points of report on cardiovascular health and diseases in China 2020[J]. Chinese Journal of Cardiovascular Research, 2021, 19(7): 582-590. (in Chinese)
[3] Song P, Zhang Y, Yu J, et al. Global prevalence of hypertension in children: A systematic review and Meta-analysis[J]. JAMA Pediatr, 2019, 173(12): 1154-1163.
[4] Dong J, Dong H, Yan Y, et al. Prevalence of hypertension and hypertension phenotypes after three visits in Chinese urban children[J]. J Hypertens, 2022, 40(7): 1270-1277.
[5] Azegami T, Uchida K, Tokumura M, et al. Blood pressure tracking from childhood to adulthood[J]. Front Pediatr, 2021, 9: 785356.
[6] Chu C, Liao YY, He MJ, et al. Blood pressure trajectories from childhood to youth and arterial stiffness in adulthood: A 30-year longitudinal follow-up study[J]. Front Cardiovasc Med, 2022, 9: 894426.
[7] Yang L, Magnussen CG, Yang L, et al. Elevated blood pressure in childhood or adolescence and cardiovascular outcomes in adulthood: A systematic review[J]. Hypertension, 2020, 75(4): 948-955.
[8] 余婷, 关德凤, 张冬萍, 等.子痫前期与肠道菌群[J].国际妇产科学杂志, 2019, 46(2):169-172.
Yu T, Guang DF, Zhang DP, et al. Preeclampsia and intestinal flora[J]. Int J Gynecol Obstet, 2019, 46(2): 169-172. (in Chinese)
[9] 魏勇军, 李晓琪, 戢博阳, 等. 肠道菌群与宿主关系解析及肠道菌群调控/合成研究进展[J].中国科学:生命科学, 2022, 52(2): 249-265.
Wei YJ, Li XQ, Mie BY, et al. Analysis of intestinal flora-host relationship and research progress in intestinal flora regulation and synthesis[J]. Sci China Life Sci, 2022, 52(2): 249-265. (in Chinese)
[10] Dan X, Mushi Z, Baili W, et al. Differential analysis of hypertension-associated intestinal microbiota[J]. Int J Med Sci, 2019, 16(6): 872-881.
[11] Palmu J,Salosensaari A,Havulinna AS, et al. Association between the gut microbiota and blood pressure in a population cohort of 6 953 individuals[J]. J Am Heart Assoc, 2020, 9(15): e016641.
[12] Lu W, Wang Y, Fang Z, et al. Bifidobacterium longum CCFM752 prevented hypertension and aortic lesion, improved antioxidative ability, and regulated the gut microbiome in spontaneously hypertensiverats[J]. Food Funct, 2022, 13(11): 6373-6386.
[13] Yan D, Sun Y, Zhou X, et al. Regulatory effect of gut microbes on bloodpressure[J]. Animal Model Exp Med, 2022, 5(6): 513-531.
[14] 米杰, 王天有, 孟玲慧, 等. 中国儿童青少年血压参照标准的研究制定[J]. 中国循证儿科杂志, 2010, 5(1): 4-14.
Mi J, Wang TY, Meng LH, et al. Development of blood pressure reference standards for Chinese children and adolescents[J]. Chin J Evid Based Pediatr, 2010, 5(1): 4-14. (in Chinese)
[15] 王文.中国血压测量指南[J].中华临床医师杂志:电子版, 2011, 6(15): 1101-1115.
Wang W.Guidelines for blood pressure measurement in China[J]. Chin J Hpertens, 2011, 6(15): 1101-1115.(in Chinese)
[16] Robles-Vera I, Toral M, De La Visitación N, et al. The probiotic lactobacillus fermentum prevents dysbiosis and vascular oxidative stress in rats with hypertension induced by chronic nitric oxideblockade[J]. Mol Nutr Food Res, 2018, 62(19): e1800298.
[17] Liu J, An N, Ma C, et al.Correlation analysis of intestinal flora with hypertension[J]. Exp Ther Med, 2018, 16(3): 2325-2330.
[18] Khalesi S, Sun J, Buys N, et al. Effect of probiotics on blood pressure:A systematic review and Meta-analysis of randomized, controlled trials[J]. Hypertension, 2014, 64(4): 897-903.
[19] Zhao TX, Zhang L, Zhou N, et al. Long-term use of probiotics for the management of office and ambulatory blood pressure: A systematic review and meta-analysis of randomized, controlledtrials[J]. Food Sci Nutr, 2022, 11(1): 101-113.
[20] Barbara G,Barbaro MR, Fuschi D, et al. Inflammatory and microbiota-related regulation of the intestinal epithelial barrier[J]. Front Nutr, 2021, 8: 718356.
[21] Muralitharan R, Marques FZ. Diet-related gut microbial metabolites and sensing inhypertension[J]. J Hum Hypertens, 2021, 35(2): 162-169.
[22] Jiang S, Shui Y, Cui Y, et al. Gut microbiota dependent trimethylamine N-oxide aggravates angiotensin II-induced hypertension[J]. Redox Biol, 2021,46: 102115.
[23] Vallianou NG, Geladari E, Kounatidis D. Microbiome and hypertension: Where are we now?[J]. J Cardiovasc Med (Hagerstown),2020, 21(2): 83-88.
[24] Dinakis E, Nakai M, Gill P, et al. Association between the gut microbiome and their metabolites with human blood pressure variability[J]. Hypertension,2022, 79(8):1690-1701.
基金
广州市科技计划青年项目(202102020967)