CLINICAL TRIAL article
Front. Psychiatry
Sec. Mood Disorders
This article is part of the Research TopicGut Microbiome Influences in Mood Disorders: Unveiling the Gut-Brain AxisView all 8 articles
Effects of in vitro fermentation of Astragalus polysaccharide on gut microbiota and neurotransmitter metabolites in patients with major depressive disorder
Provisionally accepted
Chen Lin1
Yuwei Mi1
HuoWang Zheng2
Yanbin Hou1
Jieqiong Hu1JiaXin Mao1Ni Dai1ChaoLang Fu3*XiaoQiong Li2*YunXin Ji1*- 1Ningbo First Hospital, Ningbo, China
- 2Zhejiang Academy of Agricultural Sciences, Hangzhou, China
- 3Ningbo Haishu District People's Hospital, Ningbo, China
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Background: Major depressive disorder (MDD) is a common and heterogeneous mental illness with an unclear pathogenesis and often suboptimal treatment outcomes. Astragalus polysaccharide (APS) has shown potential antidepressant effects and may serve as a functional food; however, its impact on the gut microbiota and metabolome in MDD remains unexplored. Methods: Using an in vitro fermentation model coupled with 16S rRNA sequencing and targeted metabolomics, we characterized the gut microbial composition and neurotransmitter metabolites in fecal samples from 15 MDD patients and 15 healthy subjects. Results: MDD samples exhibited elevated Fusobacteriaecae and Eggerthellaceae, reduced levels of Eubacterium hallii, Faecalibacterium, and Ruminococcus, and higher concentrations of glutamine (Gln) and glutamate (Glu). APS fermentation significantly increased Bifidobacterium and Lactobacillus while decreasing Eubacterium hallii and Bilophila, without increasing the total gas volume, CO2，and H2S production. Additionally, beneficial metabolites were elevated in MDD samples after APS addition, including glutamine (Gln), γ-aminobutyric acid (GABA), dopamine (DA), and 5-hydroxytryptophan (5-HTP). The increase in GABA among healthy subjects was more significant. Conclusions: These findings indicate that MDD is associated with disruptions in gut microbiota and Glu/GABA metabolism. When APS are applied directly to the colon, they may mitigate these disruptions by modulating microbial composition and key neuroactive metabolites, thereby influencing the central nervous system via the gut-brain axis. This effect appears to be more pronounced in healthy individuals.
Keywords: Astragalus polysaccharide, Depression, gamma-Aminobutyric Acid, Gut Microbiota, In vitro fermentation, Metabolites
Received: 24 Nov 2025; Accepted: 02 Feb 2026.
Copyright: © 2026 Lin, Mi, Zheng, Hou, Hu, Mao, Dai, Fu, Li and Ji. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
ChaoLang Fu
XiaoQiong Li
YunXin Ji
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