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

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...

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Main Authors: Silvia Diviccaro, Valentina Caputi, Lucia Cioffi, Silvia Giatti, Joshua M. Lyte, Donatella Caruso, Siobhain M. O’Mahony, Roberto Cosimo Melcangi
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/22/12551
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author Silvia Diviccaro
Valentina Caputi
Lucia Cioffi
Silvia Giatti
Joshua M. Lyte
Donatella Caruso
Siobhain M. O’Mahony
Roberto Cosimo Melcangi
author_facet Silvia Diviccaro
Valentina Caputi
Lucia Cioffi
Silvia Giatti
Joshua M. Lyte
Donatella Caruso
Siobhain M. O’Mahony
Roberto Cosimo Melcangi
author_sort Silvia Diviccaro
collection DOAJ
description 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.
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spelling doaj.art-5562d33f45b841fd84d431d9e8d3f2032023-11-22T23:44:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122221255110.3390/ijms222212551Exploring the Impact of the Microbiome on Neuroactive Steroid Levels in Germ-Free AnimalsSilvia Diviccaro0Valentina Caputi1Lucia Cioffi2Silvia Giatti3Joshua M. Lyte4Donatella Caruso5Siobhain M. O’Mahony6Roberto Cosimo Melcangi7Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, ItalyAPC Microbiome Ireland, University College Cork, T12 YT20 Cork, IrelandDipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, ItalyDipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, ItalyAPC Microbiome Ireland, University College Cork, T12 YT20 Cork, IrelandDipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, ItalyAPC Microbiome Ireland, University College Cork, T12 YT20 Cork, IrelandDipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, ItalySteroid 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.https://www.mdpi.com/1422-0067/22/22/12551liquid chromatography–tandem mass spectrometryhippocampuscerebellumcerebral cortexhypothalamusplasma
spellingShingle Silvia Diviccaro
Valentina Caputi
Lucia Cioffi
Silvia Giatti
Joshua M. Lyte
Donatella Caruso
Siobhain M. O’Mahony
Roberto Cosimo Melcangi
Exploring the Impact of the Microbiome on Neuroactive Steroid Levels in Germ-Free Animals
International Journal of Molecular Sciences
liquid chromatography–tandem mass spectrometry
hippocampus
cerebellum
cerebral cortex
hypothalamus
plasma
title Exploring the Impact of the Microbiome on Neuroactive Steroid Levels in Germ-Free Animals
title_full Exploring the Impact of the Microbiome on Neuroactive Steroid Levels in Germ-Free Animals
title_fullStr Exploring the Impact of the Microbiome on Neuroactive Steroid Levels in Germ-Free Animals
title_full_unstemmed Exploring the Impact of the Microbiome on Neuroactive Steroid Levels in Germ-Free Animals
title_short Exploring the Impact of the Microbiome on Neuroactive Steroid Levels in Germ-Free Animals
title_sort exploring the impact of the microbiome on neuroactive steroid levels in germ free animals
topic liquid chromatography–tandem mass spectrometry
hippocampus
cerebellum
cerebral cortex
hypothalamus
plasma
url https://www.mdpi.com/1422-0067/22/22/12551
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