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目的:探讨肠道嗜黏蛋白阿克曼菌(AKK)人群分布特征及其和肥胖关系的剂量效应,为该菌用于肥胖干预提供参考。方法:纳入2008年广东肠道微生物组计划中6 986名包含体重指数、腰围及常见混杂因素包括年龄、性别、舒张压、收缩压、空腹血糖、三酰甘油、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、尿酸的志愿者。根据细菌16S核糖体RNA(16S rRNA)基因测序信息,计算AKK属及其操作分类单元(OTUs)丰度;根据2002年中国肥胖工作组标准,诊断中心性或全身性肥胖。通过多变量n logistic回归,计算AKK菌每升高一个单位,患肥胖风险的n OR(95%n CI)值;通过比较AKK菌第1~20分位数n OR值的变化估计AKK对肥胖的剂量效应。n 结果:共注释到3种AKK菌(AKKn OTU1、AKKn OTU2、AKKn OTU3):AKKn OTU1及AKKn OTU2分布于90%以上人群;AKKn OTU3分布于21.7%的人群中;3种OTUs均呈“双峰”分布,但和常见混杂因素的相关性具有差异。AKKn OTU1、AKKn OTU2及AKK属为肥胖的保护因素,对中心性肥胖的n OR(95%n CI)分别为0.95(0.93~0.98)、0.97(0.94~0.99)、0.93(0.91~0.96),对全身性肥胖的n OR(95%n CI)分别为0.88(0.80~0.97)、0.98(0.93~1.02)、0.81(0.74~0.89);该保护效应在调整常见混杂因素后仍然显著。通过剂量分析可知,AKK菌对中心性肥胖和全身性肥胖的保护效应随其浓度升高而增加,达到显著保护作用的最小剂量分别为1.83%和4.98%。n 结论:AKK菌是肥胖的保护因素,但肥胖干预需要考虑AKK菌剂量效应及不同菌种/株水平的差异。“,”Objective:Investigating the distribution of intestinal Akkermansia muciniphila (AKK) and explore abundance-effect in obesity obesity to provide potential dose effect for obesity intervention.Methods:Clinical data of 6 986 subjects including body mass index, waist circumference, and common confounders such as gender, age, diastolic blood pressure, systolic blood pressure, fasting blood glucose, triglyceride, total cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, and uric acid were collected from Guangdong Gut Microbiome Project in 2008. 16S ribosomal RNA (16S rRNA) sequencing data were used to estimate the genus abundance of AKK as well as its operational taxonomic unites (OTUs). Central obesity and overall obesity were diagnosed according to the criteria of China Obesity Working Group in 2002. Multivariate logistic regression was used to analyze the n OR (95%n CI) of obesity with one-unite elevation of AKK. The dose effect of AKK on obesity was estimated by comparing the trend of n ORs from the 1st to the 20th quantile.n Results:A total of three AKK OTUs(AKKn OTU1, AKKn OTU2, AKKn OTU3) were identified: AKKn OTU1 and AKKn OTU2 were distributed in more than 90% of the population, while AKKn OTU3 was distributed at 21.7%; All the OTUs showed a“bimodal”distributional pattern and their correlations with common factors were variable. Disparities of the association with obesity were found between the OTUs and the AKK. AKKn OTU1, AKKn OTU2, and the genus level of AKK showed significant protective effects against obesity; The n ORs (95%n CI) were 0.95(0.93-0.98), 0.97(0.94-0.99), 0.93(0.91-0.96), respectively for central obesity; And ORs(95%n CI) were 0.88(0.80-0.97), 0.98(0.93-1.02), 0.81(0.74-0.89), respectively for overall obesity. The results were similar after adjustment for common confounders. According to the calculation of dose-effect, the protect effects of AKK increased with accumulated abundance and the minimum effective dose on central obesity and overall obesity was 1.83% and 4.98%, respectively.n Conclusion:AKK is a protective factor for obesity, but the dose-effect of AKK and the strain-differences should be considered in the future interventional study.