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Gut Microflora & Estrogens

Gut microflora and estrogens: a new paradigm for breast cancer risk reduction?

PIs: Lusine Yaghjyan, MD, MPH, PhD (University of Florida) & Kathleen M. Egan, PhD (H. Lee Moffitt Cancer Center)

Approximately 100 trillion microorganisms live in our bodies and most are found in our intestines. In fact, the microorganism population in our bodies is 10 times larger than the total number of our somatic and germ cells. The microbiota helps to protect us from pathogens, exerts important metabolic functions, and regulates inflammatory response by stimulating the immune system. Commensal gut microbes are thus integral to health and emerging science indicates that microbial imbalance (‘dysbiota’) from diet or use or antibiotics may contribute to disease, including cancer. In particular, a hypothesis being studied in this FACCA project is that the gut microbiome, by altering circulating estrogen levels, contributes to the risk for breast cancer.

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With funding from the Florida Academic Cancer Center Alliance, breast cancer epidemiologists Dr. Lusine Yaghjyan at the University of Florida and Dr. Kathleen Egan at Moffitt Cancer Center are collaborating on a novel investigation that explores whether the composition of the gut microbiome impacts estrogen levels after menopause. For their study, the investigators are characterizing the gut microbiome in fecal specimens and relating measured profiles with estrogen metabolites in urine. Women for this study are identified through high-volume mammography clinics at Moffitt. Eligible women (a total of 100 to be enrolled) are postmenopausal, have no recent use of antibiotics or postmenopausal hormones, no history of breast cancer or metabolic or hepatic disorders, or chronic intestinal problems, and have a body mass index≤30 kg/m2. All women provide stool and spot urine sample, and complete a detailed questionnaire. The microbiome in stool samples is assayed at UF Health using a state-of-the art DNA sequencing methods in the laboratory of study co-investigator, Dr. Volker Mai, epidemiology faculty at UF. Estrogens in urinary samples are measured at Moffitt with liquid chromatography-selected reaction monitoring mass spectrometry (LC-SRM) by study co-investigator, Dr. John Koomen, Proteomics Core director at Moffitt. Further expertise in microbiotal profiles in relation to cancer is provided by the study co-investigator, Dr. Christine Pierce-Campbell, epidemiologist at Moffitt. These complex data will be analyzed by another UF co-investigator, Dr. Mattia Prosperi, who is an expert in analyzing large multidimensional datasets.

The collaborative framework made possible with FACCA support allows investigators to take advantage of unique institutional resources and expertise at the two Florida’s cancer centers conducting the research. Findings from this pilot study will be instrumental in planning definitive investigations to establish the gut microbiome as an important and here-to-fore unrecognized determinant of endogenous estrogen levels and, by extension, breast cancer risk. The project thus has high potential for public health impact and may ultimately lead to lifestyle and bio-therapeutic interventions that can be applied to reduce breast cancer risk.