Intestinal dysbacteriosis has frequently been involved in the context of depression. Nonetheless, only scant information is available about the features and functional changes of gut microbiota in female middle-aged depression (MAD). This study aims to explore whether there are characteristic changes in the gut microbes of female MAD and whether these changes are associated with depressive-like behaviors. Meanwhile, this study observed alterations in the lipid metabolism function of gut microbes and further examined changes in plasma medium- and long-chain fatty acids (MLCFAs) in mice that underwent fecal microbiota transplantation (FMT). Stool samples obtained from 31 MAD, along with 24 healthy individuals (HC) were analyzed by 16 S rRNA gene sequencing. Meanwhile, 14-month-old female C57BL/6J mice received antibiotic cocktails and then oral gavage of the microbiota suspension of MAD or HC for 3 weeks to reconstruct gut microbiota. The subsequent depressive-like behaviors, the composition of gut microbiota, as well as MLCFAs in the plasma were evaluated. A noteworthy disruption in gut microbial composition in MAD individuals compared to HC was observed. Several distinct bacterial taxa, including , , and , demonstrated associations with the demographic variables. A particular microbial panel encompassing 49 genera effectively differentiated MAD patients from HC (AUC = 0.82). Fecal microbiome transplantation from MAD subjects led to depressive-like behaviors and dysfunction of plasma MLCFAs in mice. These findings suggest that microbial dysbiosis is linked to the pathogenesis of MAD, and its role may be associated with the regulation of MLCFAs metabolism.

中文翻译：

---

患有抑郁症的中年女性的肠道微生物组调节雌性中年小鼠的抑郁样行为和血浆脂肪酸代谢

肠道菌群失调经常与抑郁症有关。尽管如此，关于女性中年抑郁症（MAD）肠道微生物群的特征和功能变化的信息很少。本研究旨在探讨女性 MAD 的肠道微生物是否存在特征性变化，以及这些变化是否与抑郁样行为相关。同时，本研究观察了肠道微生物脂质代谢功能的变化，并进一步检测了接受粪便微生物移植（FMT）的小鼠血浆中链和长链脂肪酸（MLCFA）的变化。通过 16 S rRNA 基因测序分析从 31 名 MAD 和 24 名健康个体 (HC) 获得的粪便样本。同时，14 个月大的雌性 C57BL/6J 小鼠接受抗生素混合物，然后口服 MAD 或 HC 微生物悬浮液 3 周，以重建肠道微生物群。对随后的抑郁样行为、肠道微生物群的组成以及血浆中的 MLCFA 进行了评估。与 HC 相比，MAD 个体的肠道微生物组成发生了显着的破坏。几个不同的细菌类群，包括 、 、 和 ，证明了与人口统计变量的关联。包含 49 个属的特定微生物组可有效区分 MAD 患者和 HC (AUC = 0.82)。 MAD 受试者的粪便微生物组移植导致小鼠出现抑郁样行为和血浆 MLCFA 功能障碍。这些发现表明微生物失调与 MAD 的发病机制有关，其作用可能与 MLCFA 代谢的调节有关。