Neonatal exposure to androgens dynamically alters gut microbiota architecture

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 neo...

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Detalles Bibliográficos
Autores: Barroso, Alexia, Santos Marcos, José A., Perdices López, Cecilia, Vega Rojas, Ana, Sánchez Garrido, Miguel Ángel, Krylova, Yelizabeta, Molina Abril, Helena, Ohlsson, Claes, Pérez Martínez, Pablo, Poutanen, Matti, López Miranda, José, Tena Sempere, Manuel, Camargo, Antonio
Tipo de recurso: artículo
Estado:Versión enviada para evaluación y publicación
Fecha de publicación:2020
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/114715
Acceso en línea:https://hdl.handle.net/11441/114715
https://doi.org/10.1530/JOE-20-0277
Access Level:acceso abierto
Palabra clave:Gut microbiota
Hormones
Sex steroids
Metabolic diseases
Obesity
Descripción
Sumario: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 altera tions of the sex steroid profile later on life, namely lower progesterone and higher estr adiol 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, a nd 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.