Gut Microbes Linked to Estrogen Breakdown in Menopause

Beth Skwarecki

September 15, 2014

Postmenopausal women with a more diverse population of gut bacteria may be more efficient at breaking down estrogen, a new study suggests. Because estrogen plays a role in causing breast cancer, researchers speculate a healthy bacterial population may lower the risk for cancer.

"[T]he composition and diversity of the intestinal microbiota were associated with patterns of estrogen metabolism that are predictive of the risk of breast cancer in postmenopausal women," Barbara J. Fuhrman, PhD, from the Department of Epidemiology, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, and colleagues write in an article published online September 11 in the Journal of Clinical Endocrinology and Metabolism.

Estrogen is metabolized in the liver and in other tissues such as the breast, yielding fragments that are excreted in urine or, through bile, into the gut. Gut microbes can degrade these metabolites, allowing them to be reabsorbed into the bloodstream and further recycled in the liver. Dr. Fuhrman and colleagues suggest that women whose gut bacteria more efficiently process estrogen may have a lowered risk for breast cancer.

The study involved 60 postmenopausal women who were members of Kaiser Permanente Colorado. Their age ranged from 55 to 70 years, 91% were white, and subjects' median body mass index was 27 kg/m2. All had had a normal mammogram within the previous 8 weeks. The women gave fecal samples to be surveyed via pyrosequencing for bacterial diversity, as well as urine samples to examine the ratio of estrogen to estrogen metabolites.

Patients with more diversity of microbes in their fecal samples had higher ratios of metabolites to parent estrogen (P for trend = .004). However, the association only held for 1 of the 3 diversity measures they used, called whole-tree phylogenetic diversity, and not for 2 common ways of measuring bacterial diversity, the Simpson and Shannon indices. Bacteria of the class Clostridia, and especially the genus Ruminococcus, were significantly associated with high metabolite ratios (P = .04), and those in the genus Bacteroides were inversely related (P = .03), although these P-values were not adjusted for multiple comparisons and the authors write that these associations "must be considered exploratory."

Because the study relied on sequencing 16S ribosomal RNA, rather than whole-genome sequencing or functional assays, the investigators could not determine how or whether microbes are responsible for the differences seen in estrogen metabolites. They write that their findings "provide an early step toward the ultimate goal of understanding how the gut microbiota may affect estrogen homeostasis and its impact on human health."

The authors have disclosed no relevant financial relationships.

J Clin Endocrinol Metabol. Published online September 11, 2014. Abstract

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