High dietary copper intake induces perturbations in the gut microbiota and affects host ovarian follicle development

Qi Wang; Yan Sun; Aili Zhao; Xuefen Cai; Aili Yu; Qian Xu; Weili Liu; Nan Zhang; Siyi Wu; Yiqin Chen; Wenxiang Wang

doi:10.1016/j.ecoenv.2023.114810

High dietary copper intake induces perturbations in the gut microbiota and affects host ovarian follicle development

Ecotoxicol Environ Saf. 2023 Apr 15:255:114810. doi: 10.1016/j.ecoenv.2023.114810. Epub 2023 Mar 20.

Authors

Qi Wang¹, Yan Sun², Aili Zhao³, Xuefen Cai⁴, Aili Yu⁴, Qian Xu³, Weili Liu³, Nan Zhang³, Siyi Wu³, Yiqin Chen³, Wenxiang Wang⁵

Affiliations

¹ Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China; Department of Health Statistics, School of Public Health and Health Management, Gannan Medical University, Ganzhou, China.
² Center for Reproductive Medicine, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China; Fujian Province Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China.
³ Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China.
⁴ Center for Reproductive Medicine, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China.
⁵ Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China; Fujian Province Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China. Electronic address: wangwenxiang@fjmu.edu.cn.

PMID: 36948015
DOI: 10.1016/j.ecoenv.2023.114810

Abstract

Increasing evidence has shown that gut microbes play an important role in the reproductive endocrine system and the development of polycystic ovary syndrome (PCOS). However, whether environmental factors are involved in these gut microbiota alterations has seldom been studied. In this study, we aimed to explore the crucial role of an imbalanced gut microbiota on abnormal ovarian follicle development induced by Cu. A 1:1 matched case-control study with 181 PCOS patients and 181 controls was conducted using a propensity score matching protocol. Information regarding dietary Cu intake was obtained from a face-to-face dietary intake interview. Alterations in the gut microbiota were detected by high-throughput 16 S rDNA sequencing. The results showed that dietary Cu intake was positively correlated with the risk of PCOS, and the risk threshold was approximately 1.992 mg/d. Compared with those with dietary Cu intakes lower than 1.992 mg/d, those who had a higher dietary Cu intake had a 1.813-fold increased risk of PCOS (OR=1.813, 95% CI: 1.150-2.857). PCOS patients had a lower relative abundance of Bacteroides than controls (P = 0.003), and Bacteroides played a partial mediating role between dietary Cu exposure and PCOS (P_{indirect effect}=0.026, 95% CI: 0.002-0.072). In addition, an animal model of Cu exposure through the diet showed that Cu can induce gut microbiota disorder; increase serum levels of LPS, MDA, and IL-6; and alter host ovarian steroidogenesis to affect ovarian follicle development. Staphylococcus played a partial mediating role between Cu exposure and CYP17A1 (P_{g_Staphylococcus}=0.083, 95% CI: 0.001-0.228). Overall, this study shows that long-term exposure to high dietary Cu levels can affect the composition of the gut microbiota, cause inflammation and oxidative stress, and then interfere with hormone signaling, ultimately affecting ovarian follicle development.

Keywords: 16S rDNA sequencing; Bacteroides; Copper; Polycystic ovary syndrome; Staphylococcus.

MeSH terms

Animals
Case-Control Studies
Copper / toxicity
Female
Gastrointestinal Microbiome*
Humans
Ovarian Follicle
Polycystic Ovary Syndrome*

Substances

Copper