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The host-steroid-microbiome axis: Microbial remodeling of steroid scaffolds and its implications for metabolic and
Thanga Y Gajendiran1, Nila Ganamurali2, Sarvesh Sabarathinam3
1Medical Student (Year III), Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Tamil Nadu, Chennai, 602105, India.
Abstract:
Steroids, chemically conserved yet functionally diverse, integrate metabolic, endocrine and microbial networks. Beyond host hormones acting via specific receptors, the gut microbiome edits steroid scaffolds, yielding metabolites that reshape systemic signaling. We introduce the host-steroid-microbiome axis, framing steroids as holobiont currencies coordinating metabolism, immunity and endocrine balance. This continuum links endogenous steroidogenesis, microbial transformations (via hydroxysteroid dehydrogenases, sulfatases and β-glucuronidases) and host receptor modulation (farnesoid X, Takeda G protein-coupled receptor 5 (TGR5), estrogen, androgen and glucocorticoid receptors), impacting bile acid signaling, glucose/lipid metabolism and hormone-related diseases. Steroidomics, multiomics, Cryogenic electron microscopy (cryo-EM), artificial intelligence (AI) modeling and digital twins illuminate these interactions, enabling precision endocrinology informed by the microbiome, diet and genetics. A roadmap unites microbial ecology, steroid chemistry and AI for therapeutic targeting.
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