Gender affirming hormone therapy preserves skeletal maturation in young mice via the gut microbiome

微生物群 肠道微生物群 激素 激素疗法 生理学 生物 生物信息学 医学 内分泌学 内科学 癌症 乳腺癌
作者
Subhashis Pal,Xochitl C. Morgan,Hamid Y. Dar,Camilo Anthony G. Gacasan,Sudha Patil,Andreea Stoica,Yi‐Juan Hu,M. Neale Weitzmann,Rheinallt Jones,Roberto Pacifici
出处
期刊:Journal of Clinical Investigation [American Society for Clinical Investigation]
标识
DOI:10.1172/jci175410
摘要

Gender affirming hormone therapy (GAHT) is often prescribed to transgender (TG) adolescents to alleviate gender dysphoria, but the impact of GAHT on the growing skeleton is unclear. We found GAHT to improve trabecular bone structure via increased bone formation in young male mice and not to affect trabecular structure in female mice. GAHT modified gut microbiome composition in both male and female mice. However, fecal microbiota transfers (FMT) revealed that GAHT-shaped gut microbiome was a communicable regulator of bone structure and turnover in male, but not in female mice. Mediation analysis identified two species of Bacteroides as significant contributors to the skeletal effects of GAHT in male mice, with Bacteroides supplementation phenocopying the effects of GAHT on bone. Bacteroides have the capacity to expand Treg populations in the gut. Accordingly, GAHT expanded intestinal regulatory T cells (Tregs) and stimulated their homing to the bone marrow (BM) in male but not in female mice. Attesting to the functional relevance of Tregs, pharmacological blockade of Treg expansion prevented GAHT-induced bone anabolism. In summary, in male mice GAHT stimulated bone formation and improved trabecular structure by promoting Treg expansion via a microbiome-mediated effect. In female mice GAHT neither improved nor impaired trabecular structure.
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