Exploring the Impact of the Microbiome on Neuroactive Steroid Levels in Germ-Free Animals

• Published in: International journal of molecular sciences 2021-11, Vol.22 (22), p.12551
• Main Authors: Diviccaro, Silvia, Caputi, Valentina, Cioffi, Lucia, Giatti, Silvia, Lyte, Joshua M, Caruso, Donatella, O'Mahony, Siobhain M, Melcangi, Roberto Cosimo
• Format: Article
• Language: English
• Subjects: Androstane-3,17-diol - analogs & derivatives; Androstane-3,17-diol - blood; Animal models; Animals; Biomolecules; Brain; Brain - metabolism; Cerebellum; Cerebral cortex; Chromatography; Communication; Dehydroepiandrosterone; Dihydrotestosterone; Dihydrotestosterone - blood; Endocrine system; Gastrointestinal Microbiome - genetics; Gender differences; Germ Cells - metabolism; Germfree; Gonadal Steroid Hormones - blood; Gonadal Steroid Hormones - genetics; Hippocampus; Hormone replacement therapy; Hormones; Hypothalamus; Intestinal microflora; Liquid chromatography; liquid chromatography–tandem mass spectrometry; Male; Mass spectrometry; Mass spectroscopy; Mice; Microbiomes; Microbiota; Microbiota - genetics; Microorganisms; Nervous system; Neuromodulation; Neurosteroids; Neurosteroids - blood; Neurosteroids - metabolism; Physiology; Plasma; Pregnanolone; Pregnanolone - blood; Pregnanolone - metabolism; Steroid hormones; Steroids; Tandem Mass Spectrometry; Testosterone; Testosterone - metabolism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222212551

Steroid hormones are essential biomolecules for human physiology as they modulate the 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 the plasma of germ-free (GF) male mice and conventionally colonized controls. The data obtained indicate an increase in allopregnanolone levels associated with a decrease in those of 5α-androstane-3α, 17β-diol (3α-diol) in the 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 3α-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.