OBJECTIVE: 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).
METHODS: 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.
RESULTS: A noteworthy disruption in gut microbial composition in MAD individuals compared to HC was observed. Several distinct bacterial taxa, including Dorea, Butyricicoccus, and Blautia, 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.
CONCLUSIONS: 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.
目的: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,这项研究观察了肠道微生物脂质代谢功能的变化,并进一步检查了接受粪便微生物移植(FMT)的小鼠血浆中链和长链脂肪酸(MLCFAs)的变化。
方法:从31MAD中获得的粪便样本,通过16SrRNA基因测序分析了24名健康个体(HC)。同时,14个月大的雌性C57BL/6J小鼠接受抗生素鸡尾酒,然后口服灌胃MAD或HC的微生物群悬浮液3周以重建肠道微生物群。随后的类似抑郁的行为,肠道微生物群的组成,以及血浆中的MLCFA进行了评估。
结果:与HC相比,观察到MAD个体的肠道微生物组成的显著破坏。几种不同的细菌分类群,包括Dorea,Butyricicocus,还有Blautia,证明了与人口统计学变量的关联。包含49属的特定微生物组有效区分MAD患者与HC(AUC=0.82)。MAD受试者的粪便微生物组移植导致小鼠血浆MLCFA的抑郁样行为和功能障碍。
结论:这些发现表明微生物菌群失调与MAD的发病机制有关,其作用可能与MLCFAs代谢的调节有关。