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双歧杆菌和木聚糖的共生治疗促进肠道衍生的吲哚-3-丙酸,并改善阿尔茨海默病小鼠模型的认知障碍。

Synbiotic therapy with and xylan promotes gut-derived indole-3-propionic acid and improves cognitive impairments in an Alzheimer's disease mouse model.

机构信息

Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China.

College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China.

出版信息

Food Funct. 2024 Jul 29;15(15):7865-7882. doi: 10.1039/d4fo00886c.


DOI:10.1039/d4fo00886c
PMID:38967039
Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized primarily by cognitive impairment. Recent investigations have highlighted the potential of nutritional interventions that target the gut-brain axis, such as probiotics and prebiotics, in forestalling the onset of AD. In this study, whole-genome sequencing was employed to identify xylan as the optimal carbon source for the tryptophan metabolism regulating probiotic (). Subsequent studies demonstrated that administration of a synbiotic formulation comprising (1 × 10 CFU per day) and xylan (1%, w/w) over a duration of 30 days markedly enhanced cognitive performance and spatial memory faculties in the 5xFAD transgenic AD mouse model. The synbiotic treatment significantly reduced amyloid-β (Aβ) accumulation in the cortex and hippocampus of the brain. Importantly, synbiotic therapy substantially restored the synaptic ultrastructure in AD mice and suppressed neuroinflammatory responses. Moreover, the intervention escalated levels of the microbial metabolite indole-3-propionic acid (IPA) and augmented the relative prevalence of IPA-synthesizing bacteria, and , while reducing the dominant bacteria in AD, such as , , and . Notably, synbiotic treatment also prevented the disruption of gut barrier integrity. Correlation analysis indicated a strong positive association between gut microbiota-generated IPA levels and behavioral changes. In conclusion, this study demonstrates that synbiotic supplementation significantly improves cognitive and intellectual deficits in 5xFAD mice, which could be partly attributed to enhanced IPA production by gut microbiota. These findings provide a theoretical basis for considering synbiotic therapy as a novel microbiota-targeted approach for the treatment of metabolic and neurodegenerative diseases.

摘要

阿尔茨海默病(AD)是一种进行性神经退行性疾病,主要表现为认知障碍。最近的研究强调了营养干预措施的潜力,这些措施可以针对肠道-大脑轴,例如益生菌和益生元,以预防 AD 的发生。在这项研究中,全基因组测序用于鉴定木聚糖作为色氨酸代谢调节益生菌()的最佳碳源。随后的研究表明,在 30 天的时间内,每天给予包含(每天 1×10 CFU)和木聚糖(1%,w/w)的合生元配方可显著改善 5xFAD 转基因 AD 小鼠模型的认知表现和空间记忆能力。合生元治疗显著减少了大脑皮质和海马体中的淀粉样蛋白-β(Aβ)积累。重要的是,合生元疗法大大恢复了 AD 小鼠的突触超微结构,并抑制了神经炎症反应。此外,干预措施提高了微生物代谢产物吲哚-3-丙酸(IPA)的水平,并增加了 IPA 合成菌和的相对流行率,同时减少了 AD 中的优势菌,如、和。值得注意的是,合生元治疗还防止了肠道屏障完整性的破坏。相关性分析表明,肠道微生物群产生的 IPA 水平与行为变化之间存在很强的正相关关系。总之,本研究表明,合生元补充剂可显著改善 5xFAD 小鼠的认知和智力缺陷,这可能部分归因于肠道微生物群产生的 IPA 增强。这些发现为将合生元治疗作为一种新型针对肠道微生物群的代谢和神经退行性疾病治疗方法提供了理论依据。

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引用本文的文献

[1]
Gut-brain axis modulation in remote rehabilitation of Parkinson's disease: reconstructing the fecal metabolome and nigral network connectivity.

Front Neurol. 2025-8-15

[2]
The role of probiotics, prebiotics, and postbiotics: cellular and molecular pathways activated on glial cells in Alzheimer's disease.

Front Neurosci. 2025-6-25

[3]
Tryptophan-Rich Diet Improves High-Fat Diet-Induced Cognitive Dysfunction and Blood-Brain Barrier Disruption in C57BL/6 Mice through FFAR3 Activation.

J Agric Food Chem. 2025-7-16

[4]
The microbiota-gut-brain axis and central nervous system diseases: from mechanisms of pathogenesis to therapeutic strategies.

Front Microbiol. 2025-6-13

[5]
Synbiotics of Lactobacillus suilingensis and inulin alleviates cognitive impairment via regulating gut microbiota indole-3-lactic acid metabolism in female AD mice.

Alzheimers Dement. 2025-7

[6]
Microbiome Engineering for Biotherapeutic in Alzheimer's Disease Through the Gut-Brain Axis: Potentials and Limitations.

Int J Mol Sci. 2025-6-2

[7]
and Galacto-Oligosaccharides Synbiotic Relieve Irritable Bowel Syndrome by Reshaping Gut Microbiota and Attenuating Mast Cell Hyperactivation.

Nutrients. 2025-5-14

[8]
Indolepropionic acid modulates the immune response in allergic rhinitis through the AKT/CEBPB/IL‑10 signaling pathway.

Mol Med Rep. 2025-7

[9]
The Impact of the Exposome on Alzheimer's Disease: The Influence of Nutrition.

Int J Mol Sci. 2025-3-26

[10]
Diverse Physiological Roles of Kynurenine Pathway Metabolites: Updated Implications for Health and Disease.

Metabolites. 2025-3-20

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