DataSheet_2_Obese Individuals With and Without Phlegm-Dampness Constitution Show Different Gut Microbial Composition Associated With Risk of Metabolic Disorders.pdf

BackgroundObesity is conventionally considered a risk factor for multiple metabolic diseases, such as dyslipidemia, type 2 diabetes, hypertension, and cardiovascular disease (CVD). However, not every obese patient will progress to metabolic disease. Phlegm-dampness constitution (PDC), one of the nine TCM constitutions, is considered a high-risk factor for obesity and its complications. Alterations in the gut microbiota have been shown to drive the development and progression of obesity and metabolic disease, however, key microbial changes in obese patients with PDC have a higher risk for metabolic disorders remain elusive.
MethodsWe carried out fecal 16S rRNA gene sequencing in the present study, including 30 obese subjects with PDC (PDC), 30 individuals without PDC (non-PDC), and 30 healthy controls with balanced constitution (BC). Metagenomic functional prediction of bacterial taxa was achieved using PICRUSt.
ResultsObese individuals with PDC had higher BMI, waist circumference, hip circumference, and altered composition of their gut microbiota compared to non-PDC obese individuals. At the phylum level, the gut microbiota was characterized by increased abundance of Bacteroidetes and decreased levels of Firmicutes and Firmicutes/Bacteroidetes ratio. At the genus level, Faecalibacterium, producing short-chain fatty acid, achieving anti-inflammatory effects and strengthening intestinal barrier functions, was depleted in the PDC group, instead, Prevotella was enriched. Most PDC-associated bacteria had a stronger correlation with clinical indicators of metabolic disorders rather than more severe obesity. The PICRUSt analysis demonstrated 70 significantly different microbiome community functions between the two groups, which were mainly involved in carbohydrate and amino acid metabolism, such as promoting Arachidonic acid metabolism, mineral absorption, and Lipopolysaccharide biosynthesis, reducing Arginine and proline metabolism, flavone and flavonol biosynthesis, Glycolysis/Gluconeogenesis, and primary bile acid biosynthesis. Furthermore, a disease classifier based on microbiota was constructed to accurately discriminate PDC individuals from all obese people.
ConclusionOur study shows that obese individuals with PDC can be distinguished from non-PDC obese individuals based on gut microbial characteristics. The composition of the gut microbiome altered in obese with PDC may be responsible for their high risk of metabolic diseases.

背景
肥胖通常被认为是多种代谢性疾病的危险因素，例如血脂异常、2型糖尿病、高血压以及心血管疾病（cardiovascular disease，CVD）。然而，并非所有肥胖患者都会进展为代谢性疾病。痰湿体质（Phlegm-dampness constitution，PDC）作为中医九种体质之一，被认为是肥胖及其并发症的高危因素。已有研究证实，肠道菌群的改变可推动肥胖及代谢性疾病的发生发展，但伴有痰湿体质的肥胖患者发生代谢紊乱的关键菌群变化仍尚不明确。
方法
本研究开展粪便16S rRNA基因测序，纳入30例伴有痰湿体质的肥胖受试者（PDC组）、30例不伴有痰湿体质的受试者（非PDC组）以及30例体质平和的健康对照者（平和体质组，balanced constitution，BC）。采用PICRUSt完成细菌类群的宏基因组功能预测。
结果
与非PDC肥胖受试者相比，PDC组肥胖受试者的BMI、腰围、臀围更高，且肠道菌群组成发生显著改变。在门水平上，肠道菌群以拟杆菌门（Bacteroidetes）丰度升高、厚壁菌门（Firmicutes）丰度降低以及厚壁菌门/拟杆菌门比值下降为典型特征。在属水平上，产短链脂肪酸、发挥抗炎作用并强化肠道屏障功能的普拉梭菌属（Faecalibacterium）在PDC组中丰度显著降低，而普雷沃氏菌属（Prevotella）丰度显著升高。多数与痰湿体质相关的细菌与代谢紊乱的临床指标相关性更强，而非与肥胖程度更严重相关。PICRUSt分析显示，两组间共存在70个差异显著的菌群群落功能，主要涉及碳水化合物与氨基酸代谢，其中花生四烯酸代谢、矿物质吸收及脂多糖（Lipopolysaccharide）生物合成等通路在PDC组中显著上调，而精氨酸与脯氨酸代谢、黄酮与黄酮醇生物合成、糖酵解/糖异生及初级胆汁酸生物合成等通路则显著下调。此外，本研究构建了基于菌群的疾病分类器，可准确将PDC受试者与所有肥胖人群区分开来。
结论
本研究表明，基于肠道菌群特征可将伴有痰湿体质的肥胖受试者与非PDC肥胖受试者有效区分。伴有痰湿体质的肥胖人群肠道菌群组成的改变，可能是其罹患代谢性疾病高风险的重要机制。