Initiating Oral Contraception Does Not Change Gut Microbiome in Healthy Women

Human and animal evidence suggests both exogenous and endogenous sex hormones can affect the microbiome.

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Researchers at Massachusetts General Hospital recently completed the first systematic study of how the initiation of oral contraception (OC) affects the structure and function of the gut microbiome. Xinwei Hua, PhD, MPH, a research fellow in the Division of Gastroenterology at Mass General and research fellow in Medicine at Harvard Medical School, Hamed Khalili, MD, MPH, a gastroenterologist in the Clinical and Translational Epidemiology Unit, director of Clinical Research in Inflammatory Bowel Disease in the Division of Gastroenterology, and associate professor of Medicine at Harvard Medical School, and colleagues found no significant change in microbiome diversity or composition after OC initiation. However, the relative abundance of some metabolic pathways changed, as reported in the Journal of Medical Microbiology.

Methods

The longitudinal study involved 10 healthy women ages 16 to 40 who started OC use between January 2015 and August 2018. They provided blood and stool samples before initiation of OC, one month later, and six months later.

The Microbiome and Oral Contraception Use

Initiation of OC use was not linked to any significant change in microbial diversity or composition (159 species analyzed). However, OC use influenced the function of the microbiome; specifically, it was associated with significant enrichments in certain metabolic pathways (272 analyzed):

• Microbial functions involved in the synthesis of amino acids, including L-lysine, L-threonine, L-methionine, and L-tryptophan
• Synthesis of peptidoglycan, the main component of bacteria cell walls
• Metabolism of coenzymes during oxidation reactions

The Microbiome and Endogenous Sex Hormones

The team observed several significant associations between serum levels of endogenous sex hormones and the composition of the microbiome:

• Estradiol and sex hormone–binding globulin (SHBG) were positively associated with the relative abundance of Eubacterium ramulus, a flavonoid-degrading anaerobe commonly involved in fermentation in the gastrointestinal tract
• Progesterone was positively associated with the abundance of E. ventriosum
• Lower levels of estradiol and higher levels of total testosterone were associated with more abundant Megasphaera unclassified
• SHBG was negatively associated with Bifidobacterium animalis, a lactic acid–producing anaerobe

Significant associations were also noted between endogenous sex hormones and microbiome function. Specifically, several amino acid biosynthesis pathways (L-lysine, L-threonine, and L-methionine) were enriched in women who had modest decreases in endogenous levels of estradiol or SHBG or higher levels of total testosterone.

Continued Scrutiny Needed

OC use has been linked to several immune-mediated diseases, including Crohn's disease, rheumatoid arthritis, and systemic lupus erythematosus.

Here we did not observe a significant shift in the gut microbiome composition with the initiation of OC use. Interestingly, several associations between endogenous sex hormone and microbial features were observed. Future larger studies are needed to characterize the associations between OC, endogenous sex hormones, and the gut microbiome is needed.

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