Clapp Organski Anna, Reddivari Anjali, Reddivari Lavanya, Brubaker Douglas K, Fuller Kelly N Z, Thyfault John P, Cross Tzu-Wen L
Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA.
Department of Electrical and Computer Engineering, Purdue University, West Lafayette, IN 47907, USA.
Nutrients. 2025 Aug 9;17(16):2591. doi: 10.3390/nu17162591.
Oral contraceptives (OCs) containing estrogen and/or progesterone are the second most common form of female contraception in the United States. While endogenously synthesized estrogen is known to provide protective effects against cardiometabolic diseases, exogenous forms such as OCs have been linked to increased susceptibility to cardiometabolic diseases and an elevated risk of myocardial infarction. The gut microbiota is thought to be a critical regulator of cardiometabolic disease risk; however, its interactions with OC use remain understudied. We aimed to evaluate the effects of OC use on the intestinal microbiota and investigate microbial associations with intestinal estradiol levels, energy homeostasis, and hepatic oxidative stress markers. Female C57BL/6J mice were fed a high-fat diet with or without OCs from 7 to 8 weeks of age and maintained for either 12 or 20 weeks. Duodenal, jejunal, cecal, and colonic microbiota, cecal short- and branched-chain fatty acids, and intestinal estradiol levels were assessed. Both 12- and 20-week of OC treatments significantly elevated colonic estradiol levels. Twenty weeks of OC treatment significantly altered the composition of both cecal and colonic microbiota and increased cecal isobutyric acid concentrations, whereas 12 weeks of OC treatment resulted in only trending shifts in the cecal microbiota and did not alter colonic microbiota or fatty acid compositions assessed. In 12-week treated mice, cecal was positively associated with non-resting energy expenditure, whereas in 20-week treated mice, cecal was positively associated with resting energy expenditure. OC use induces time- and intestinal segment-dependent shifts in the gut microbiota and branched-chain fatty acid production. The OC-induced increase in colonic estradiol could further influence the gut microbiota and health when utilized long-term. These findings provide critical insight into how OC use may contribute to increased cardiometabolic risk through gut microbial alterations.
含有雌激素和/或孕激素的口服避孕药（OCs）是美国女性避孕的第二常见方式。虽然已知内源性合成的雌激素对心脏代谢疾病具有保护作用，但外源性形式如OCs却与心脏代谢疾病易感性增加以及心肌梗死风险升高有关。肠道微生物群被认为是心脏代谢疾病风险的关键调节因子；然而，其与OCs使用之间的相互作用仍未得到充分研究。我们旨在评估OCs使用对肠道微生物群的影响，并研究微生物与肠道雌二醇水平、能量稳态和肝脏氧化应激标志物之间的关联。雌性C57BL/6J小鼠在7至8周龄时喂食含或不含OCs的高脂饮食，并维持12周或20周。评估十二指肠、空肠、盲肠和结肠微生物群、盲肠短链和支链脂肪酸以及肠道雌二醇水平。OCs治疗12周和20周均显著提高结肠雌二醇水平。OCs治疗20周显著改变了盲肠和结肠微生物群的组成，并增加了盲肠异丁酸浓度，而OCs治疗12周仅导致盲肠微生物群出现趋势性变化，并未改变结肠微生物群或所评估的脂肪酸组成。在接受12周治疗的小鼠中，盲肠[此处原文缺失相关内容]与非静息能量消耗呈正相关，而在接受20周治疗的小鼠中，盲肠[此处原文缺失相关内容]与静息能量消耗呈正相关。OCs的使用会引起肠道微生物群和支链脂肪酸产生随时间和肠道节段的依赖性变化。长期使用OCs导致的结肠雌二醇增加可能会进一步影响肠道微生物群和健康。这些发现为OCs使用如何通过肠道微生物改变导致心脏代谢风险增加提供了关键见解。
