Neonatal exposure to androgens dynamically alters gut microbiota architecture

in Journal of Endocrinology
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  • 1 Department of Cell Biology, Physiology, and Immunology, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Reina Sofia University Hospital, Cordoba, Spain
  • 2 CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain
  • 3 Lipids and Atherosclerosis Research Unit, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
  • 4 Department of Applied Mathematics I, University of Seville, Seville, Spain
  • 5 Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
  • 6 Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland

Correspondence should be addressed to M Tena-Sempere or A Camargo: fi1tesem@uco.es or antonio.camargo@imibic.org

*(A Barroso and J A Santos-Marcos contributed equally to this work)

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Gonadal steroids strongly contribute to the metabolic programming that shapes the susceptibility to the manifestation of diseases later in life, and the effect is often sexually dimorphic. Microbiome signatures, together with metabolic traits and sex steroid levels, were analyzed at adulthood in neonatally androgenized female rats, and compared with those of control male and female rats. Exposure of female rats to high doses of androgens on early postnatal life resulted in persistent alterations of the sex steroid profile later on life, namely lower progesterone and higher estradiol and estrone levels, with no effect on endogenous androgens. Neonatally androgenized females were heavier (10% at early adulthood and 26% at adulthood) than controls and had impaired glucose homeostasis observed by higher AUC of glucose in GTT and ITT when subjected to obesogenic manipulations. Androgenized female displayed overt alterations in gut microbiota, indicated especially by higher Bacteroidetes and lower Firmicutes abundance at early adulthood, which disappeared when animals were concurrently overfed at adulthood. Notably, these changes in gut microbiota were related with the intestinal expression of several miRNAs, such as miR-27a-3p, miR-29a-5p, and miR-100-3p. Our results suggest that nutritional and hormonal disruption at early developmental periods not only alters the metabolic programming of the individual later in life but also perturbs the architecture of gut microbiota, which may interact with the host by a cross-talk mediated by intestinal miRNAs; phenomena that may contribute to amplify the metabolic derangement caused by obesity, as seen in neonatally androgenized female rats.

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