Effects of in vitro fermentation of Astragalus polysaccharide on gut microbiota and neurotransmitter metabolites in patients with major depressive disorder

TL;DR

This study explores how Astragalus polysaccharide affects gut bacteria and brain-related chemicals in people with depression, suggesting potential benefits for mental health.

Contribution

The novel contribution is the first exploration of Astragalus polysaccharide's impact on gut microbiota and neurotransmitter metabolites in MDD patients using in vitro fermentation.

Findings

MDD samples showed altered gut bacteria and higher glutamine and glutamate levels.

APS increased beneficial bacteria like Bifidobacterium and Lactobacillus while reducing harmful ones.

APS elevated key brain chemicals like GABA and dopamine, especially in healthy individuals.

Abstract

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.

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.

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.

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.

https://www.medicalresearch.org.cn, identifier MR-33-25-010733.

Figures