RT Journal Article T1 Neonatal Androgen Exposure Causes Persistent Gut Microbiota Dysbiosis Related to Metabolic Disease in Adult Female Rats A1 Moreno-Indias, Isabel A1 Sanchez-Alcoholado, Lidia A1 Angel Sanchez-Garrido, Miguel A1 Maria Martin-Nunez, Gracia A1 Perez-Jimenez, Francisco A1 Tena-Sempere, Manuel A1 Tinahones, Francisco J. A1 Isabel Queipo-Ortuno, Maria K1 Insulin-resistance K1 Energy-balance K1 Body-fat K1 Testosterone K1 Obesity K1 Bacteria K1 Impact K1 Diet K1 Estradiol K1 Estrogens AB Alterations of gut microbiome have been proposed to play a role in metabolic disease, but the major determinants of microbiota composition remain ill defined. Nutritional and sex hormone challenges, especially during early development, have been shown to permanently alter adult female phenotype and contribute to metabolic disturbances. In this study, we implemented largescale microbiome analyses to fecal samples from groups of female rats sequentially subjected to various obesogenic manipulations, including sex hormone perturbations by means of neonatal and rogenization or adult ovariectomy (OVX), as a model of menopause, to establish whether these phenomena are related to changes in gut microbiota. Basic metabolic profiles concerning glucose/insulin homeostasis were also explored. The effects of the sex hormonal perturbations, either developmentally (androgenization) or in adulthood (OVX), clearly outshone the impact of nutritional interventions, especially concerning the gut microbiota profile. Notably, we observed a lower diversity in the androgenized group, with the highest Firmicutes to Bacteroidetes ratio, supporting the occurrence of durable alterations in gut microbiota composition, even in adulthood. Moreover, the elimination of adult ovarian secretions by OVX affected the richness of gut microbiota. Our data are the first to document the durable impact of sex steroid manipulations, and particularly early androgenization, on gut microbiota composition. Such dysbiosis is likely to contribute to the metabolic perturbations of conditions of obesity linked to gonadal dysfunction in the female. PB Oxford univ press inc SN 0013-7227 YR 2016 FD 2016-12-01 LK http://hdl.handle.net/10668/19138 UL http://hdl.handle.net/10668/19138 LA en DS RISalud RD Apr 11, 2025