Association of breast and gut microbiota dysbiosis and the risk of breast cancer: a case-control clinical study Plaza Díaz, Julio Álvarez Mercado, Ana Isabel Ruiz Marín, Carmen Reina Pérez, Iris Pérez Alonso, Alejandro José Torné Poyatos, Pablo Gallart Aragón, Tania Sánchez-Barrón, María Teresa Reyes Lartategui, S. de García, Federico Chueca-Porcuna, Natalia Sáez Lara, María José Robles-Sánchez, Candido Fernández, Mariana F. Fontana Gallego, Luis Archaea Bacteria Breast cancer Breast microbiota Endocrine disruptors Environmental pollutants Fungi Gut microbiota Virus We would like to thank M Luisa Puertas-Martin and Isabel Manzano-Jimenez, nurses at the Unit of Mammary Pathology, General Surgery Service, San Cecilio University Hospital (Granada), without whose enthusiasm the enrolment of participants in Granada would still be stalled. We are indebted to all the women taking part in the study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Trial registration ClinicalTrials.gov NCT03885648, 03/25/2019. Retrospectively registered. Background Breast cancer ranks first in women, and is the second cause of death in this gender. In addition to genetics, the environment contributes to the development of the disease, although the factors involved are not well known. Among the latter is the influence of microorganisms and, therefore, attention is recently being paid to the mammary microbiota. We hypothesize that the risk of breast cancer could be associated with the composition and functionality of the mammary/gut microbiota, and that exposure to environmental contaminants (endocrine disruptors, EDCs) might contribute to alter these microbiota. Methods We describe a case-control clinical study that will be performed in women between 25 and 70 years of age. Cases will be women diagnosed and surgically intervened of breast cancer (stages I and II). Women with antecedents of cancer or advanced tumor stage (metastasis), or who have received antibiotic treatment within a period of 3 months prior to recruitment, or any neoadjuvant therapy, will be excluded. Controls will be women surgically intervened of breast augmentation or reduction. Women with oncological, gynecological or endocrine history, and those who have received antibiotic treatment within a period of 3 months prior to recruitment will also be excluded. Blood, urine, breast tissue and stool samples will be collected. Data regarding anthropometric, sociodemographic, reproductive history, tumor features and dietary habits will be gathered. Metabolomic studies will be carried out in stool and breast tissue samples. Metagenomic studies will also be performed in stool and breast tissue samples to ascertain the viral, fungal, bacterial and archaea populations of the microbiota. Quantitation of estrogens, estrogen metabolites and EDCs in samples of serum, urine and breast tissue will also be performed. Discussion: This is the first time that the contribution of bacteria, archaea, viruses and fungi together with their alteration by environmental contaminants to the risk of breast cancer will be evaluated in the same study. Results obtained could contribute to elucidate risk factors, improve the prognosis, as well as to propose novel intervention studies in this disease. 2020-05-11T12:48:18Z 2020-05-11T12:48:18Z 2019-05-24 info:eu-repo/semantics/article Plaza-Díaz, J., Álvarez-Mercado, A.I., Ruiz-Marín, C. et al. Association of breast and gut microbiota dysbiosis and the risk of breast cancer: a case-control clinical study. BMC Cancer 19, 495 (2019). [https://doi.org/10.1186/s12885-019-5660-y] http://hdl.handle.net/10481/61954 10.1186/s12885-019-5660-y eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España Springer Nature