Menopause Is Associated with an Altered Gut Microbiome and Estrobolome, with Implications for Adverse Cardiometabolic Risk in the Hispanic Community Health Study/Study of Latinos.
Menopause Is Associated with an Altered Gut Microbiome and Estrobolome, with Implications for Adverse Cardiometabolic Risk in the Hispanic Community Health Study/Study of Latinos.
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DOI：
10.1128/msystems.00273-22
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发表时间：
2022-06-28
期刊：
影响因子：
6.4
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中科院分区：
文献类型：
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更年期是一个关键时期，在此期间卵巢激素的损失会增加心脏代谢风险，也可能影响肠道微生物组。然而，绝经期与微生物组的关系尚未在大型研究中进行研究，其对心脏代谢疾病的影响尚不清楚。在西班牙裔社区健康研究/拉丁裔研究中，心脏代谢风险因素负担高的人群，对2，300名参与者（295名绝经前女性，1，027名绝经后女性和978名男性）的粪便进行了鸟枪宏基因组测序，并在一个子集上提供了血清代谢组学。在针对年龄和其他人口统计学/行为协变量调整的模型中，与绝经前女性相比，绝经后女性倾向于降低肠道微生物组多样性并改变整体组成，而与男性的差异较小。绝经后妇女与绝经前妇女的丰度不同的分类群包括拟杆菌属菌株Ga6 A1、马氏普雷沃氏菌和瓦德斯苏泰氏菌（在绝经后富集）和大肠杆菌-志贺氏菌属，振荡杆菌属菌株KLE 1745、嗜粘蛋白阿克曼氏菌、乳酸发酵梭菌、约氏副杆菌和阴道韦荣球菌（绝经后耗竭）;这些分类群在男性和女性之间也存在类似差异。绝经后妇女的微生物硫酸盐转运系统丰度较高，微生物β-葡萄糖醛酸酶丰度降低;这些功能与血清中的维生素B1代谢物相关，表明绝经后肠道微生物参与性激素潴留。在绝经后女性中，绝经相关的微生物组改变与不良心脏代谢特征相关。总而言之，在大量的美国西班牙裔/拉丁裔人口中，更年期与肠道微生物组更类似于男性，可能与低雌激素/孕激素状态的常见状况有关。未来的工作应研究其他种族/族裔群体中结果的相似性。绝经过渡期以卵巢激素下降为标志，被认为是心脏代谢风险的关键时期。肠道微生物群与性激素代谢相互作用，但缺乏将更年期与肠道微生物群联系起来的大规模人群研究。我们对西班牙裔/拉丁裔女性和男性进行的一项大型研究结果表明，女性绝经后肠道微生物组与男性肠道微生物组略微相似，绝经会消耗特定的肠道病原体，并降低肠道微生物组的代谢潜力。同时，肠道微生物可能参与绝经后妇女性激素的重新激活和保留。绝经相关的肠道微生物组变化与绝经后妇女的不良心脏代谢风险相关，表明肠道微生物组有助于绝经期间心脏代谢健康的变化。
Menopause is a pivotal period during which loss of ovarian hormones increases cardiometabolic risk and may also influence the gut microbiome. However, the menopause-microbiome relationship has not been examined in a large study, and its implications for cardiometabolic disease are unknown. In the Hispanic Community Health Study/Study of Latinos, a population with high burden of cardiometabolic risk factors, shotgun metagenomic sequencing was performed on stool from 2,300 participants (295 premenopausal women, 1,027 postmenopausal women, and 978 men), and serum metabolomics was available on a subset. Postmenopausal women trended toward lower gut microbiome diversity and altered overall composition compared to premenopausal women, while differing less from men, in models adjusted for age and other demographic/behavioral covariates. Differentially abundant taxa for post- versus premenopausal women included Bacteroides sp. strain Ga6A1, Prevotella marshii, and Sutterella wadsworthensis (enriched in postmenopause) and Escherichia coli-Shigella spp., Oscillibacter sp. strain KLE1745, Akkermansia muciniphila, Clostridium lactatifermentans, Parabacteroides johnsonii, and Veillonella seminalis (depleted in postmenopause); these taxa similarly differed between men and women. Postmenopausal women had higher abundance of the microbial sulfate transport system and decreased abundance of microbial β-glucuronidase; these functions correlated with serum progestin metabolites, suggesting involvement of postmenopausal gut microbes in sex hormone retention. In postmenopausal women, menopause-related microbiome alterations were associated with adverse cardiometabolic profiles. In summary, in a large U.S. Hispanic/Latino population, menopause is associated with a gut microbiome more similar to that of men, perhaps related to the common condition of a low estrogen/progesterone state. Future work should examine similarity of results in other racial/ethnic groups. IMPORTANCE The menopausal transition, marked by declining ovarian hormones, is recognized as a pivotal period of cardiometabolic risk. Gut microbiota metabolically interact with sex hormones, but large population studies associating menopause with the gut microbiome are lacking. Our results from a large study of Hispanic/Latino women and men suggest that the postmenopausal gut microbiome in women is slightly more similar to the gut microbiome in men and that menopause depletes specific gut pathogens and decreases the hormone-related metabolic potential of the gut microbiome. At the same time, gut microbes may participate in sex hormone reactivation and retention in postmenopausal women. Menopause-related gut microbiome changes were associated with adverse cardiometabolic risk in postmenopausal women, indicating that the gut microbiome contributes to changes in cardiometabolic health during menopause.
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