Hua Xinwei, Cao Yueming, Morgan David M, Miller Kaia, Chin Samantha M, Bellavance Danielle, Khalili Hamed
Department of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA.
J Med Microbiol. 2022 Apr;71(4). doi: 10.1099/jmm.0.001512.
Evidence has linked exogenous and endogenous sex hormones with the human microbiome. The longitudinal effects of oral contraceptives (OC) on the human gut microbiome have not previously been studied. We sought to examine the longitudinal impact of OC use on the taxonomic composition and metabolic functions of the gut microbiota and endogenous sex steroid hormones after initiation of OC use. We recruited ten healthy women who provided blood and stool samples prior to OC use, 1 month and 6 months after starting OC. We measured serum levels of sex hormones, including estradiol, progesterone, sex hormone-binding globulin (SHBG), and total testosterone. Shotgun metagenomic sequencing was performed on DNA extracted from faecal samples. Species and metabolic pathway abundances were determined using MetaPhlAn2 and HUMAnN2. Multivariate association with linear models was used to identify microbial species and metabolic pathways associated with OC use and endogenous levels of sex hormones. The percentage variance of the microbial community explained by individual factors ranged from 9.9 % for age to 2.7 % for time since initiation of OC use. We observed no changes in the diversity or composition of the gut microbiome following OC initiation. However, the relative abundance of the biosynthesis pathways of peptidoglycan, amino acids (lysine, threonine, methionine, and tryptophan), and the NAD salvage pathway increased after OC initiation. In addition, serum levels of estradiol and SHBG were positively associated with a flavonoid-degrading bacterium. Similarly, microbes involving biosynthesis of l-lysine, l-threonine, and l-methionine were significantly associated with lower estradiol, SHBG, and higher levels of total testosterone. Our study provides the first piece of evidence supporting the association between exogenous and endogenous sex hormones and gut microbiome composition and function.
有证据表明外源性和内源性性激素与人类微生物群有关。口服避孕药（OC）对人类肠道微生物群的纵向影响此前尚未得到研究。我们试图研究开始使用OC后，其对肠道微生物群的分类组成和代谢功能以及内源性性类固醇激素的纵向影响。我们招募了10名健康女性，她们在开始使用OC之前、开始使用OC后1个月和6个月提供血液和粪便样本。我们测量了性激素的血清水平，包括雌二醇、孕酮、性激素结合球蛋白（SHBG）和总睾酮。对从粪便样本中提取的DNA进行鸟枪法宏基因组测序。使用MetaPhlAn2和HUMAnN2确定物种和代谢途径的丰度。使用线性模型进行多变量关联分析，以识别与OC使用和内源性性激素水平相关的微生物物种和代谢途径。个体因素解释的微生物群落方差百分比从年龄的9.9%到开始使用OC后的时间的2.7%不等。我们观察到开始使用OC后肠道微生物群的多样性或组成没有变化。然而，开始使用OC后，肽聚糖、氨基酸（赖氨酸、苏氨酸、蛋氨酸和色氨酸）的生物合成途径以及NAD补救途径的相对丰度增加。此外，雌二醇和SHBG的血清水平与一种黄酮降解细菌呈正相关。同样，参与l-赖氨酸、l-苏氨酸和l-蛋氨酸生物合成的微生物与较低的雌二醇、SHBG水平以及较高的总睾酮水平显著相关。我们的研究提供了首个证据，支持外源性和内源性性激素与肠道微生物群组成和功能之间的关联。
