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