Implication of gut microbiota in the association between infant antibiotic exposure and childhood obesity and adiposity accumulation
Implication of gut microbiota in the association between infant antibiotic exposure and childhood obesity and adiposity accumulation
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肠道微生物群在婴儿抗生素暴露与儿童肥胖和肥胖积累之间的关系中的意义
DOI：
10.1038/s41366-020-0572-0
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发表时间：
2020-04-22
影响因子：
4.9
通讯作者：
Lee, Yung Seng
中科院分区：
文献类型：
--
作者：
Chen, Ling-Wei;Xu, Jia;Lee, Yung Seng
在动物研究中，早期抗生素暴露会通过微生物群破坏导致代谢异常，包括肥胖，但来自人类研究的证据很少。我们研究了肠道菌群在婴儿抗生素暴露和儿童肥胖之间的关系。方法采用问卷调查的方式，采用父母报告的方式对婴儿第一年抗生素暴露情况进行调查。主要结局是儿童肥胖[体重指数（BMI） z-score >第95百分位]和肥胖[腹围（AC）和皮褶（三头肌+肩胛下（SST））测量]从15-60个月确定。在24个月大时，当肠道微生物群更加稳定时，收集粪便样本（n = 392），使用共丰度网络进行肠道微生物群分析。使用多重逻辑回归和线性混合效应回归评估抗生素暴露与肥胖和肥胖的关系（n = 1016）。通过部分冗余分析和多元线性关联模型确定与抗生素暴露相关的关键细菌。结果38%的研究婴儿有抗生素暴露。在一个完全调整的模型中，观察到15-60月龄时任何抗生素暴露的肥胖几率更高[OR(95% CI) = 1.45(1.001, 2.14)]，暴露于bb0 = 3个疗程的抗生素[2.78(1.12,6.87)]。对于连续肥胖指标，任何抗生素暴露与男孩较高的BMI z-score相关[β = 0.15(0.01, 0.28)]，但与女孩无关[β = -0.04(-0.19, 0.11)] （P交互作用= 0.026）。同样，暴露于>= 3个疗程的抗生素与男孩较高的AC相关[1.15(0.05,2.26)cm]，而与女孩无关[0.57(-1.32,2.45)cm] （P交互作用无显著性）。在以哈利真杆菌为代表的微生物共丰组（CAG）中，反复暴露抗生素与显著降低相关（fdr校正P值< 0.05），其比例与儿童肥胖呈负相关。同时，以Tyzzerella 4为代表的CAG与重复使用抗生素和儿童肥胖呈正相关。结论：婴儿抗生素暴露与肠道微生物群的破坏以及儿童肥胖和肥胖增加的风险增加有关。
Background In animal studies early life antibiotic exposure causes metabolic abnormalities including obesity through microbiota disruption, but evidence from human studies is scarce. We examined involvement of gut microbiota in the associations between infant antibiotic exposure and childhood adiposity. Methods Infant antibiotic exposure in the first year of life was ascertained using parental reports during interviewer-administered questionnaires. Primary outcomes were childhood obesity [body mass index (BMI) z-score > 95th percentile] and adiposity [abdominal circumference (AC) and skinfold (triceps + subscapular (SST)) measurements] determined from ages 15-60 months. At age 24 months, when the gut microbiota are more stable, stool samples (n = 392) were collected for the gut microbiota profiling using co-abundancy networks. Associations of antibiotic exposure with obesity and adiposity (n = 1016) were assessed using multiple logistic and linear mixed effects regressions. Key bacteria associated with antibiotics exposure were identified by partial redundancy analysis and multivariate association with linear models. Results Antibiotic exposure was reported in 38% of study infants. In a fully adjusted model, a higher odds of obesity from 15-60 months of age was observed for any antibiotic exposure [OR(95% CI) = 1.45(1.001, 2.14)] and exposure to >= 3 courses of antibiotics [2.78(1.12, 6.87)]. For continuous adiposity indicators, any antibiotic exposure was associated with higher BMI z-score in boys [beta = 0.15(0.01, 0.28)] but not girls [beta = -0.04(-0.19, 0.11)] (P interaction = 0.026). Similarly, exposure to >= 3 courses of antibiotics was associated with higher AC in boys [1.15(0.05, 2.26) cm] but not girls [0.57(-1.32, 2.45) cm] (P interaction not significant). Repeated exposure to antibiotics was associated with a significant reduction (FDR-corrected P values < 0.05) in a microbial co-abundant group (CAG) represented by Eubacterium hallii, whose proportion was negatively correlated with childhood adiposity. Meanwhile, a CAG represented by Tyzzerella 4 was positively correlated with the repeated use of antibiotics and childhood adiposity. Conclusions Infant antibiotic exposure was associated with disruption of the gut microbiota and the higher risks of childhood obesity and increased adiposity.