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Microbial fermentation of traditional Chinese medicine YA3D3 ameliorates cognitive impairment in APP/PS1 mice by regulating the gut microbiota-short-chain fatty acids-neurotransmitter axis
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Tian YANG, Bingyan LU, Siyao LIANG, Changwu YUE*, Yuhong LYU*
Acta Microbiologica Sinica | 2026, 66(3) : 1373 - 1393
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Acta Microbiologica Sinica | 2026, 66(3): 1373-1393
• Research Article •
Microbial fermentation of traditional Chinese medicine YA3D3 ameliorates cognitive impairment in APP/PS1 mice by regulating the gut microbiota-short-chain fatty acids-neurotransmitter axis
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Tian YANG, Bingyan LU, Siyao LIANG, Changwu YUE*, Yuhong LYU*
Affiliations
  • Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, Yan’an Medical College, Yan’an University, Yan’an, Shaanxi, China
Published: 2026-03-04 doi: 10.13343/j.cnki.wsxb.20250861
Outline
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Objective To investigate the mechanism by which the microbial fermentation product of the traditional Chinese medicine YA3D3 (YA3D3-MHF) improves cognitive function in the APP/PS1 transgenic mouse model of Alzheimer’s disease (AD) via the microbiota-gut-brain axis. Methods APP/PS1 mice were administered either the water extract of YA3D3 (YA3D3-HF) or YA3D3-MHF for 90 days. The gut microbiota structure was analyzed by 16S rRNA gene sequencing, and the fecal levels of short-chain fatty acids (SCFAs) were assessed by GC-MS. The neurotransmitter content in the brain tissue was measured via ELISA, and cognitive function was assessed via the Morris water maze. Network pharmacology and mass spectrometry were employed to identify active components and changes in chemical composition. Results Compared with the model group and the YA3D3-HF group, YA3D3-MHF significantly ameliorated cognitive impairment in mice. The Morris water maze test showed that the high-dose YA3D3-MHF (MH) group had the shortest escape latency and the highest number of platform crossings, approaching the performance of the normal control group. ELISA confirmed that the MH group had the highest levels of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), and glutamate (GLU) in the brain. The results of 16S rRNA gene sequencing revealed that the MH group exhibited the highest alpha diversity (Shannon index≈3.2) of gut microbiota and the highest abundance of beneficial bacteria, along with the lowest abundance of pro-inflammatory bacteria. GC-MS analysis indicated that the MH group had the highest levels of total SCFAs, acetate, and butyrate. MS demonstrated that YA3D3-MHF components exhibited reduced polarity and the emergence of new high-activity peaks. Conclusion YA3D3-MHF improves cognitive function in AD mice by modulating the gut microbiota-SCFAs-neurotransmitter axis, outperforming YA3D3-HF. This study provides experimental evidence for AD intervention targeting the gut-brain axis.

Alzheimer’s disease  /  traditional Chinese medicine YA3D3  /  microbiota-gut-brain axis  /  gut microbiota  /  short-chain fatty acids  /  microbial fermentation
Tian YANG, Bingyan LU, Siyao LIANG, Changwu YUE, Yuhong LYU. Microbial fermentation of traditional Chinese medicine YA3D3 ameliorates cognitive impairment in APP/PS1 mice by regulating the gut microbiota-short-chain fatty acids-neurotransmitter axis[J]. Acta Microbiologica Sinica, 2026 , 66 (3) : 1373 -1393 . DOI: 10.13343/j.cnki.wsxb.20250861
Funding
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  • Yan’an City Science and Technology Fund(2024-SFGG-201)
  • Yan’an City Science and Technology Fund(2023SLZDCY-199)
  • Yan’an University’s Production, Cultivation Project(CXY202001)
  • Yan’an University Qin Chuanyuan “Scientist+Engineer” Team Special(2023KXJ-012)
  • Yan’an University Transformation of Scientific and Technological Achievements Project(2023CGZH-001)
Appendix
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Year 2026 volume 66 Issue 3
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Article Info
doi: 10.13343/j.cnki.wsxb.20250861
  • Receive Date：2025-11-18
  • Online Date：2026-03-12
  • Published：2026-03-04
Article Data
Affiliations
History
  • Received：2025-11-18
  • Accepted：2025-12-09
Funding
Yan’an City Science and Technology Fund(2024-SFGG-201)
Yan’an City Science and Technology Fund(2023SLZDCY-199)
Yan’an University’s Production, Cultivation Project(CXY202001)
Yan’an University Qin Chuanyuan “Scientist+Engineer” Team Special(2023KXJ-012)
Yan’an University Transformation of Scientific and Technological Achievements Project(2023CGZH-001)
Affiliations
    Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, Yan’an Medical College, Yan’an University, Yan’an, Shaanxi, China

Corresponding:

*E-mail: YUE Changwu,
LYU Yuhong,
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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