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

IF 13 1区 医学 Q1 CLINICAL NEUROLOGY
Cong Yang, Jingxi Sun, Ling Li, Jin Zheng, Chuhan Wang, Yu Zhao, Duo Yun, Mengzhen Jia, Zhinan Wu, Hewei Liang, Wenxi Li, Tongyuan Hu, Rui Guo, Liang Xiao, Yuanqiang Zou, Zhigang Liu
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引用次数: 0

Abstract

INTRODUCTION

Recent studies have found that gut microbial tryptophan metabolism is altered in Alzheimer's disease (AD) patients. However, the functional consequences of these changes and their therapeutic potential remain unclear.

METHODS

The metagenomic data of 49 preclinical AD patients and 115 healthy controls were analyzed. A synbiotic with targeted metabolic functions was formulated based on in vitro testing, and its effect on AD was evaluated using female 5×FAD mice.

RESULTS

Indole lactic acid (ILA) synthesis was downregulated in AD patients. Synbiotic treatment combining Lactobacillus suilingensis and inulin outperformed probiotic treatment alone in enhancing tryptophan metabolism, and increasing ILA biosynthesis. Increased ILA could reduce Aβ accumulation and significantly alleviate cognitive impairment in female AD mice by inhibiting neuroinflammation through activation of the aryl hydrocarbon receptor (AhR) signaling pathway.

DISCUSSION

This study highlights the therapeutic potential of targeting gut microbial tryptophan metabolism in AD and provides a rationale for future precision strategies aimed at modulating microbiota-derived metabolic pathways.

Highlights

  • Gut metagenomic analysis reveals reduced indole lactic acid (ILA) biosynthesis genes in preclinical AD patients.
  • Screening and formulating ILA-producing synbiotic by using whole-genome analysis.
  • Synbiotic treatment alleviates cognitive impairment and promotes ILA synthesis in female 5×FAD mice.
  • ILA alleviates neuroinflammation in female 5×FAD mice by activating aryl hydrocarbon receptor (AhR) in the brain.
  • Synbiotic targeting tryptophan metabolism provides a novel approach for Alzheimer's intervention.

Abstract Image

乳酸菌和菊粉通过调节肠道菌群吲哚-3-乳酸代谢减轻雌性AD小鼠认知功能障碍
最近的研究发现阿尔茨海默病(AD)患者肠道微生物色氨酸代谢发生改变。然而,这些变化的功能后果及其治疗潜力仍不清楚。方法分析49例临床前AD患者和115名健康对照者的宏基因组数据。在体外实验的基础上,配制了一种具有靶向代谢功能的合成物,并利用5×FAD雌性小鼠评价其对AD的作用。结果AD患者吲哚乳酸(ILA)合成水平下调。在促进色氨酸代谢和增加ILA生物合成方面,与单独益生菌处理相比,suilingenbacillus and inulinin联合处理优于益生菌处理。增加ILA可通过激活芳烃受体(aryl hydrocarbon receptor, AhR)信号通路抑制神经炎症,从而减少Aβ积累,显著减轻雌性AD小鼠认知功能障碍。本研究强调了在AD中靶向肠道微生物色氨酸代谢的治疗潜力,并为未来旨在调节微生物衍生代谢途径的精确策略提供了理论基础。肠道宏基因组分析显示临床前AD患者的吲哚乳酸(ILA)生物合成基因减少。利用全基因组分析筛选和配方合成ila。合成治疗可减轻雌性5×FAD小鼠的认知障碍并促进ILA合成。ILA通过激活大脑中的芳烃受体(AhR)减轻雌性5×FAD小鼠的神经炎症。合成靶向色氨酸代谢为阿尔茨海默病的干预提供了一种新的途径。
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来源期刊
Alzheimer's & Dementia
Alzheimer's & Dementia 医学-临床神经学
CiteScore
14.50
自引率
5.00%
发文量
299
审稿时长
3 months
期刊介绍: Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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