|DIVICCARO, SILVIA - University Of Milan|
|CAPUTI, VALENTINA - University Of Arkansas|
|CIOFFI, LUCIA - University Of Milan|
|GIATTI, SILVIA - University Of Milan|
|Lyte, Joshua - Josh|
|CARUSO, DONATELLA - University Of Milan|
|O'MAHONY, SIOBHIAN - University College Cork|
|MELCANGI, ROBERTO - University Of Milan|
Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/17/2021
Publication Date: 11/21/2021
Citation: Diviccaro, S., Caputi, V., Cioffi, L., Giatti, S., Lyte, J.M., Caruso, D., O'Mahony, S.M., Melcangi, R.C. 2021. Exploring the impact of the microbiome on neuroactive steroid levels in germ-free animals. International Journal of Molecular Sciences. 22(22). Article 12551. https://doi.org/10.3390/ijms222212551.
Interpretive Summary: The gut microbiota, which are the collection of bacteria found in the gut, have been shown to affect the development of the central nervous system (including the brain) of animals. One route by which the microbiota affect brain development is through production of hormones, or regulation of host production of hormones. Little is known, however, how a class of these hormones called steroids are influenced by the microbiota, We therefore sought to investigate whether levels of hormones known to affect brain development were different between germ-free (i.e. animals that completely lack a microbiota) and conventional (i.e. animals with a microbiota) mice. We found that germ-free mice had significantly different levels of steroids in the brain and in the blood when compared to their conventional counterparts. These results demonstrate that the microbiota affects steroid hormone concentrations in the brain and sites outside the central nervous system (e.g. circulation). These findings establish a basis to investigate microbiota-based strategies to address aspects of normal brain development that involve steroid hormone physiological systems.
Technical Abstract: Steroid hormones are essential biomolecules for human physiology as they modulate endocrine system, nervous function and behaviour. Recent studies have shown that the gut microbiota is directly involved in the production and metabolism of steroid hormones in the periphery. However, the influence of the gut microbiota on levels of steroids acting and present in the brain (i.e., neuroactive steroids) is not fully understood. Therefore, using liquid chromatography tandem-mass spectrometry we assessed the levels of several neuroactive steroids in various brain areas and plasma of germ-free (GF) mice and conventionally colonized controls. Data obtained indicate an increase of allopregnanolone levels associated with a decrease of those of 5a-androstane-3a, 17ß-diol (3a-diol) in plasma of GF mice. Moreover, an increase of dihydroprogesterone and isoallopregnanolone in the hippocampus, cerebellum, and cerebral cortex was also reported. Changes in dihydrotestosterone and 3a-diol levels were also observed in the hippocampus of GF mice. In addition, an increase in dehydroepiandrosterone was associated with a decrease in testosterone levels in the hypothalamus of GF mice. Our findings suggest that the absence of microbes affects the neuroactive steroids in the periphery and the brain, supporting the evidence of a microbiota-mediated modulation of neuroendocrine pathways involved in preserving host brain functioning.