高血压人群肠道微生物的代谢组学分析

目的 探究高血压人群和非高血压人群间肠道微生物和微生物代谢物的差异。方法 入组2017年3月至2018年6月复旦大学附属中山医院心血管内科住院的77例非冠心病参与者，根据血压情况分为非高血压组（n=22，男性：86.4%，平均年龄：59岁）和高血压组（n=55，男性：78.2%，平均年龄：63岁）。收集两组人群的粪便样本和血液样本，通过宏基因组高通量测序对肠道菌群进行分析，通过靶向代谢组技术测定粪样本中短链脂肪酸和血液循环胆碱通路代谢物含量，比较两组参与者菌群构成及其代谢物的差异。结果 非高血压组参与者的α多样性显著高于高血压组参与者，两组间β多样性无统计学意义上的差异。在物种层面上，发现肠道中14种菌的相对丰度在两组间存在显著差异，包括单形巨单胞菌（Megamonas funiformis）、多枝梭菌（Clostridium ramosum）等。根据这些差异菌构建了肠道微生物综合评分，此评分每增加一个标准差，人群中高血压患者的相应占比降低76%。血液中的肠道微生物参与产生的氧化三甲胺相关代谢物以及粪便中的短链脂肪酸代谢物在两组间无显著差异。差异菌与代谢物相关性分析发现毛螺旋菌（Parasutterella excrementihominis）与短链脂肪酸代谢物呈负相关，与氧化三甲胺呈正相关。结论 非高血压人群和高血压人群肠道菌群有差异，本研究结果为进一步探索高血压与肠道菌群之间的关联以及治疗和预防高血压及其相关疾病提供新线索。

An exploratory analysis of the relationship between gut microbiota and hypertension

Objective To explore the difference in gut microbiota composition and microbial metabolites between hypertensive and normotensive participants. Methods From March 2017 to June 2018, 77 patients who were free of coronary heart disease and admitted in the Cardiology Department of Zhongshan Hospital, Fudan University were recruited. According to participants'' blood pressure levels, they were categorized into the normotensive group (n=22) and the hypertensive group (n=55). Stool and blood samples from each participant were collected. Our study profiled the microbial community through shotgun metagenomic sequencing and measured fecal short-chain fatty acids and circulating metabolites from choline pathway using targeted metabolomics technology. Results Significantly higher alpha diversity was observed in the normotensive participants compared with the hypertensive participants. However, their beta diversity was not statistically significant different from each other. At the species level, the relative abundance of fourteen bacteria (e.g., Megamonas funiformis and Clostridium ramosum) was differential between the two groups. Per standard deviation increase in a composite microbiota score, which was constructed on these 14 differential species, was associated with 76% lower odds of hypertension. Besides, circulating levels of trimethylamine N-oxide-related metabolites and fecal levels of short-chain fatty acids were not significantly different between the two groups. Correlation analysis of differential bacteria and metabolites showed that Parasutterella excrementihominis was positively associated with trimethylamine N-oxide and inversely associated with short-chain fatty acids. Conclusion Gut microbiota disturbance was observed in the hypertensive population. Our results may provide new clues for further studies on hypertension and gut microbiota and offer new prospects for treating and preventing hypertension.