Exploring bacterial metabolites in microbe-human host dialogue and their therapeutic potential in Alzheimer's diseases.

IF 3.9 2区化学 Q2 CHEMISTRY, APPLIED Molecular Diversity Pub Date : 2024-11-05 DOI:10.1007/s11030-024-11028-y

Sarangthem Dinamani Singh, Pankaj Bharali, Selvaraman Nagamani

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Abstract

Neurological dysfunction in association with aging, dementia, and cognitive impairment is the major cause of Alzheimer's disease (AD). Current AD therapies often yield unsatisfactory results due to their poor mechanism in treating the underlying mechanism of the disease. Recent studies suggested that metabolites from the gut microbiota facilitate brain-gut communication. A systematic network pharmacology study and the structure- and analog-based approaches are employed to investigate the metabolites produced by gut microbiota to treat AD. The microbiota metabolites available in the gutMGene database were considered in this study. Two servers, namely Swiss Target Prediction (STP) and Similarity Ensemble Approach (SEA), were used to identify the possible AD targets for the selected metabolites. Detailed KEGG pathway and Gene Ontology (GO) analysis on identified hub genes highlighted the importance of IL6, AKT1, and GSK3B in AD pathophysiology. MMTSp (Microbiota Metabolites Target Signaling pathways) network analysis elucidated that there is a strong relationship with microbiota (Paraprevotella xylaniphila YIT 11841, Bifidobacterium dentium, Paraprevotella clara YIT 11840, Enterococcus sp. 45, Bacteroides sp. 45, Bacillus sp. 46, Escherichia sp. 33, Enterococcus casseliflavus, Bacteroides uniformis, Alistipes indistinctus YIT 12060, Bacteroides ovatus, Escherichia sp. 12, and Odoribacter laneus YIT 12061) and AD pathogenesis. In addition to this, we performed molecular docking to study the metabolite interactions in the AD drug targets. The ADME/T properties of these metabolites were also calculated and the results are discussed in detail.

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探索微生物与人类宿主对话中的细菌代谢物及其对阿尔茨海默病的治疗潜力。

阿尔茨海默病（AD）的主要病因是与衰老、痴呆和认知障碍相关的神经功能紊乱。目前的阿兹海默病治疗方法由于在治疗该病的根本机制方面机制不完善，因此效果往往不尽如人意。最近的研究表明，来自肠道微生物群的代谢物促进了大脑与肠道之间的交流。我们采用了系统的网络药理学研究以及基于结构和类似物的方法来研究肠道微生物群产生的代谢物，以治疗 AD。本研究考虑了 gutMGene 数据库中的微生物群代谢物。研究使用了两个服务器，即瑞士目标预测（STP）和相似性集合方法（SEA），来确定所选代谢物的可能的AD靶点。对已确定的枢纽基因进行了详细的 KEGG 通路和基因本体（GO）分析，强调了 IL6、AKT1 和 GSK3B 在 AD 病理生理学中的重要性。MMTSp（微生物群代谢物靶信号通路）网络分析阐明了与微生物群（Paraprevotella xylaniphila YIT 11841、Bifidobacterium dentium、Paraprevotella clara YIT 11840、Enterococcus sp.45 Bacteroides sp.45、Bacillus sp.46、Escherichia sp.33、Enterococcus casseliflavus、Bacteroides uniformis、Alistipes indistinctus YIT 12060、Bacteroides ovatus、Escherichia sp.12、Odoribacter laneus YIT 12061）和 AD 发病机制。此外，我们还进行了分子对接，以研究代谢物与AD药物靶点的相互作用。我们还计算了这些代谢物的 ADME/T 特性，并对结果进行了详细讨论。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Diversity 化学-化学综合

CiteScore

7.30

自引率

7.90%

发文量

219

审稿时长

2.7 months

期刊介绍： Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;