Longitudinal analysis of the impact of oral contraceptive use on the gut microbiome

Abstract

Introduction. Evidence has linked exogenous and endogenous sex hormones with the human microbiome. Hypothesis/Gap statement. The longitudinal effects of oral contraceptives (OC) on the human gut microbiome have not previously been studied. Aim. 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. Methodology. 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. Results. 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 Eubacterium ramulus, 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. Conclusion. Our study provides the first piece of evidence supporting the association between exogenous and endogenous sex hormones and gut microbiome composition and function.

The menopause-related gut microbiome: associations with metabolomics, inflammatory protein markers, and cardiometabolic health in women with HIV

“…Several human studies have examined menopausal and/or sex hormone relationships with gut microbial features in general and HIV populations. [12][13][14][15][16][17][18][19][20][21][22] Most of them yielded heterogeneous results, which might be due to differences in population characteristics, such as age, ethnicity and BMI, sample sizes that ranged from 10 to 1,322 women, and sequencing approaches including FIG. 4.…”

“…Hence, it is biologically plausible that menopause may affect the gut microbiome via altering the metabolic interactions of certain gut bacteria and estrogens. 11 In recent years, studies on menopause [12][13][14][15][16][17] or sex hormones 12,13,[16][17][18][19][20][21][22] in relation to the gut microbiome have attracted much attention, but they revealed disparate patterns in taxa and functional profiles, and less is known in the context of HIV infection. Our prior work in the Women's Interagency HIV Study (WIHS) reported that, among 432 women with and without HIV, several microbial taxa (eg, Enterobacteriales, Prevotella copri) differed by menopausal status only in WWH.…”

Causal relationship between sex hormone‐binding globulin and major depression: A Mendelian randomization study

“…There are several factors affecting SHBG levels: estrogen can increase SHBG levels; testosterone can decrease SHBG levels; age, hypothyroidism can increase SHBG levels; obesity and insulin resistance can decrease SHBG levels. 17,18 Besides, oral contraceptives can significantly increase SHBG levels in females 19 ; in males, SHBG levels decrease in the presence of obesity or diabetes. 9 Study has found that SHBG levels in women with major depression are not significantly altered, 20 which is consistent with the finding in this study that there is no causal relationship between SHBG and major depression in women.…”

Gut microbiome influences incidence and outcomes of breast cancer by regulating levels and activity of steroid hormones in women

“…The administration of oral contraceptives fails to alter the overall composition of gut microbiome in healthy women 61 . However, dietary changes affect microbial communities in the gut in terms of both composition and function, which may influence innate and adaptive immune systems of the host.…”

“…60 The administration of oral contraceptives fails to alter the overall composition of gut microbiome in healthy women. 61 However, dietary changes affect microbial communities in the gut in terms of both composition and function, which may influence innate and adaptive immune systems of the host. Commensals significantly impact the development and responses of the immune system, and thus, they may also affect outcomes of immunological diseases.…”