Gut microbiota and FHA - supplemental tables

The aim of our study was to assess the gut microbiota composition in patients with FHA, compare it with that of a healthy population, and evaluate the effects of hormonal replacement therapy (HRT) on it. No statistical difference was found comparing the gut microbiota alpha diversity of FHA patients at baseline and post treatment. Also the overall gut microbial composition after HRT was similar to baseline. On the contrary, the relative abundance analysis revealed specific changes after HRT. At the phylum level, Fusobacteria were significantly increased after HRT, as well as Ruminococcus and Eubacterium genera.
To identify the main factors having an impact on the gut microbiota components that showed a significant variation after HRT, we conducted a multiple linear regression where the main hormonal parameters, inflammatory variables and endometrial thickness were included. Fusobacteria, which were increased after HRT in FHA, were correlated with the reduction in some proinflammatory cytokines (i.e., IL1ra, IL4, GCSF, and CCL2; Supplemental Table S1). The increase in [Ruminococcus] gnavus group post-therapy was associated with changes in endometrial thickness, and several hormonal and cytokine mediators (Supplemental Table S2). Finally, some hormonal variables and endometrial thickness, rather than inflammatory parameters, were the most relevant associated factors with the variations of [Eubacterium] hallii group (Supplemental Table S3).

本研究旨在评估FHA（Functional Hypothalamic Amenorrhea）患者的肠道菌群组成，将其与健康人群进行对比，并评估激素替代疗法（Hormonal Replacement Therapy, HRT）对该菌群的影响。对比FHA患者基线与治疗后的肠道菌群α多样性，未发现具有统计学意义的差异；激素替代疗法治疗后的整体肠道菌群组成亦与基线相似。相较之下，相对丰度分析显示，激素替代疗法治疗后菌群出现特异性变化：在门分类水平上，梭杆菌门（Fusobacteria）的相对丰度显著升高；瘤胃球菌属（Ruminococcus）与真杆菌属（Eubacterium）的相对丰度亦显著提升。
为明确对激素替代疗法治疗后出现显著丰度变化的肠道菌群组分具有影响的核心因素，本研究开展了多元线性回归分析，纳入主要激素参数、炎症指标与子宫内膜厚度。在FHA患者中经激素替代疗法治疗后丰度升高的梭杆菌门，与部分促炎细胞因子（即IL1ra、IL4、粒细胞集落刺激因子（GCSF）、CCL2；补充表S1）的水平降低呈显著相关。治疗后[瘤胃球菌]gnavus群的丰度升高，与子宫内膜厚度变化及多种激素、细胞因子介质相关（补充表S2）。最终结果显示，与炎症指标相比，部分激素变量与子宫内膜厚度是与[真杆菌]hallii群丰度变化相关性最强的关联因素（补充表S3）。