Kim Sun-Young, Woo So-Youn, Kim Hyung-Lae, Chang Yoosoo, Ryu Seungho, Kim Han-Na
Department of Psychiatry, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea.
Department of Microbiology, College of Medicine, Ewha Womans University College of Medicine, Seoul, Republic of Korea.
J Affect Disord. 2025 May 1;376:26-35. doi: 10.1016/j.jad.2025.01.149. Epub 2025 Jan 31.
The gut-brain axis is emerging as a novel mechanism to explain depressive disorders.
We performed shotgun metagenomic sequencing of stool samples obtained from 133 individuals with depression and 532 without depression. This study examined the taxonomy, functional pathways, and predicted metabolites profiles associated with depressive symptoms, using generalized linear models. To explore links between the taxonomic and functional pathway results, we compared the relative abundance of specific species contributing to pathways significantly associated with depressive symptoms.
Taxonomic composition suggested a disruption in short-chain fatty acid (SCFA)-producing capacity of the gut microbiome in the depressed group. Pathways related to SCFA biosynthesis were also depleted in this group. Faecalibacterium prausnitzii, a well-known SCFA-producing bacterium, was significantly decreased in the depressed group and was identified as a major contributor to the depleted pathways. When inferring the metabolites related to depression from metagenomic data, higher levels of docosapentaenoic acid, stearoyl ethanolamide, putrescine, and bilirubin were more likely to be found in the depressed group.
The present findings highlight the altered gut microbiota and associated SCFA-related pathways in individuals with depression. The depletion of F. prausnitzii and its contribution to SCFA production suggest that it is a potential therapeutic target for depression.
肠-脑轴正成为解释抑郁症的一种新机制。
我们对从133名抑郁症患者和532名非抑郁症患者获取的粪便样本进行了鸟枪法宏基因组测序。本研究使用广义线性模型研究了与抑郁症状相关的分类学、功能途径和预测的代谢物谱。为了探索分类学和功能途径结果之间的联系,我们比较了对与抑郁症状显著相关的途径有贡献的特定物种的相对丰度。
分类学组成表明抑郁症组肠道微生物群产生短链脂肪酸(SCFA)的能力受到破坏。该组中与SCFA生物合成相关的途径也有所减少。普拉梭菌是一种著名的产生SCFA的细菌,在抑郁症组中显著减少,并被确定为途径减少的主要贡献者。从宏基因组数据推断与抑郁症相关的代谢物时,抑郁症组中二十二碳五烯酸、硬脂酰乙醇胺、腐胺和胆红素的水平更有可能更高。
本研究结果突出了抑郁症患者肠道微生物群的改变以及相关的SCFA相关途径。普拉梭菌的减少及其对SCFA产生的贡献表明它是抑郁症的一个潜在治疗靶点。