肠道嗜黏蛋白阿克曼菌和肥胖的非线性关系及其人群分布特征  

Distributions of gut Akkermansia muciniphila and its non-linear associations with obesity

作　　者：周起 孙杰[1] 张楠[1] 吴铸 陈晨 原慧萍[1] 朱小泉[1] 孙亮[1] Zhou Qi;Sun Jie;Zhang Nan;Wu Zhu;Chen Chen;Yuan Huiping;Zhu Xiaoquan;Sun liang(Key Laboratory of Geriatrics,Beijing Institute of Geriatrics,Institute of Geriatric Medicine,Chinese Academy of Medical Sciences,Beijing Hospital/National Center of Gerontology of National Health Commission,Beijing 100730,China)

机构地区：[1]北京医院,国家老年医学中心,国家卫生健康委北京老年医学研究所,国家卫生健康委老年医学重点实验室,中国医学科学院老年医学研究院,北京100730

出　　处：《中华内分泌代谢杂志》2022年第3期190-194,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金(81571385,91849132)。

摘　　要：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6986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logistic回归,计算AKK菌每升高一个单位,患肥胖风险的OR(95%CI)值;通过比较AKK菌第1~20分位数OR值的变化估计AKK对肥胖的剂量效应。结果共注释到3种AKK菌(AKK_(OTU1)、AKK_(OTU2)、AKK_(OTU3)):AKK_(OTU1)及AKK_(OTU2)分布于90%以上人群;AKK_(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。AKK_(OTU1)、AKK_(OTU2)及AKK属为肥胖的保护因素,对中心性肥胖的OR(95%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OR(95%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%。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 6986 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 OR(95%CI)of obesity with one-unite elevation of AKK.The dose effect of AKK on obesity was estimated by comparing the trend of ORs from the 1st to the 20th quantile.Results A total of three AKK OTUs(AKK_(OTU1),AKK_(OTU2),AKK_(OTU3))were identified:AKK_(OTU1) and AKK_(OTU2) were distributed in more than 90%of the population,while AKK_(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.AKK_(OTU1),AKK_(OTU2),and the genus level of AKK showed significant protective effects against obesity;The ORs(95%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%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.Conclusion AKK is a protectiv

关 键 词：益生菌 肥胖 嗜黏蛋白阿克曼菌 剂量效应 

分 类 号：R589.2[医药卫生—内分泌]