Exploring the Impact of the Microbiome on Neuroactive Steroid Levels in Germ-Free Animals
Silvia Diviccaro; Valentina Caputi; Lucia Cioffi; Silvia Giatti; Joshua M. Lyte; Donatella Caruso; Siobhain M. O'Mahony; Roberto Cosimo Melcangi
International Journal of Molecular Sciences2021
Summary (paraphrased)
Using LC-MS/MS, the authors measured neuroactive steroids in brain regions and plasma of germ-free male mice versus conventionally colonized controls. The absence of microbes shifted neuroactive steroid profiles in both compartments: plasma allopregnanolone rose while 3alpha-diol fell, hippocampal DHT and 3alpha-diol changed, hypothalamic DHEA rose as testosterone fell, and several brain regions showed altered dihydroprogesterone and isoallopregnanolone levels. The findings demonstrate that gut microbes modulate the neuroendocrine pathways that maintain neuroactive steroid levels in the brain, not just in the periphery.
Why it’s in the systems review
The Melcangi group is the corpus's central PFS neurosteroid laboratory; this paper extends their work from drug effects to the microbiome itself, showing that removing gut microbes reshapes brain allopregnanolone, DHT, and 3alpha-diol — the exact steroids implicated in PFS and PSSD. It is the in-corpus group's own evidence that the gut-brain axis is a neurosteroid axis, tying the axis to the corpus's existing Melcangi cluster. Open-access.
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