Research Paper Volume 12, Issue 20 pp 19979—20000

Interplay between gonadal hormones and postnatal overfeeding in defining sex-dependent differences in gut microbiota architecture

Jose A. Santos-Marcos1,2,3,4, *, , Alexia Barroso1,4,5, *, , Oriol A. Rangel-Zuñiga1,2,3,4, , Cecilia Perdices-Lopez1,4,5, , Carmen Haro6, , Miguel A. Sanchez-Garrido1,4,5, , Helena Molina-Abril7, , Claes Ohlsson8, , Pablo Perez-Martinez1,2,3,4, , Matti Poutanen8,9, , Jose Lopez-Miranda1,2,3,4, , Francisco Perez-Jimenez1,2,3,4, , Manuel Tena-Sempere1,4,5,9, , Antonio Camargo1,2,3,4, ,

  • 1 Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain
  • 2 Lipids and Atherosclerosis Research Unit, Internal Medicine Unit, Reina Sofia University Hospital, Cordoba, Spain
  • 3 Department of Medicine, University of Cordoba, Cordoba, Spain
  • 4 CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
  • 5 Department of Cell Biology, Physiology, and Immunology, University of Cordoba, Cordoba, Spain
  • 6 Institute for Sustainable Agriculture (IAS), Spanish National Research Council (CSIC), Cordoba, Spain
  • 7 Department of Applied Mathematics I, University of Seville, Seville, Spain
  • 8 Centre for Bone and Arthritis Research, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
  • 9 Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, 20014 Turku, Finland
* Equal contribution

Received: June 18, 2020       Accepted: September 20, 2020       Published: October 27, 2020
How to Cite

Copyright: © 2020 Santos-Marcos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Aging is associated with a decline in sex hormones, variable between sexes, that has an impact on many different body systems and might contribute to age-related disease progression. We aimed to characterize the sex differences in gut microbiota, and to explore the impact of depletion of gonadal hormones, alone or combined with postnatal overfeeding, in rats. Many of the differences in the gut microbiota between sexes persisted after gonadectomy, but removal of gonadal hormones shaped several gut microbiota features towards a more deleterious profile, the effect being greater in females than in males, mainly when animals were concurrently overfed. Moreover, we identified several intestinal miRNAs as potential mediators of the impact of changes in gut microbiota on host organism physiology. Our study points out that gonadal hormones contribute to defining sex-dependent differences of gut microbiota, and discloses a potential role of gonadal hormones in shaping gut microbiota, as consequence of the interaction between sex and nutrition. Our data suggest that the changes in gut microbiota, observed in conditions of sex hormone decline, as those caused by ageing in men and menopause in women, might exert different effects on the host organism, which are putatively mediated by gut microbiota-intestinal miRNA cross-talk.


CVD: cardiovascular diseases; T: testosterone; F/B: Firmicutes/Bacteroidetes; SCFA: short chain fatty acids; NL-CD: normal feeding condition; SL-HFD: postnatal overfeeding; GNX: gonadectomized; E2: estradiol; E1: estrone; AUC: area under the curve; ΔAUC: delta area under the curve; GTT: glucose tolerance test; ITT: insulin tolerance test; LEfSe: Linear discriminant analysis (LDA) effect size; CD: control diet; HFD: high-fat diet; PND: postnatal day; SL: small litter; NL: normal litter; BW: body weight.