Kaur Simranjit, Kumari Deepali, Dandekar Manoj P
Department of Biological Sciences (Pharmacology and Toxicology), National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India, 500037.
Mol Neurobiol. 2025 May;62(5):6308-6316. doi: 10.1007/s12035-024-04685-5. Epub 2025 Jan 7.
Alzheimer's disease (AD) is a major devastating neurodegenerative disorder afflicting majorly the geriatric population. Emerging studies augur the connection of gut dysbiosis and circadian disruption with the early onset of AD. Gut dysbiosis is characterized by dysregulated gut microbiota signature and compromised intestinal integrity, which provokes the translocation of bacterial metabolites into the systemic circulation. Noteworthy, gut-derived metabolites like calprotectin, trimethylamine-N-oxide, kynurenine, isoamylamine, and short-chain fatty acids play a key role in AD pathogenesis. Circadian dysregulation also corresponds with the exacerbated AD pathogenesis by accumulating Aβ and tau proteins. Moreover, circadian dysregulation is one of the causative factors for gut dysbiosis. This review discusses the complex interplay between the microbiota-gut-brain axis, circadian rhythmicity, and the emergence of AD. We reviewed preclinical and clinical studies on AD describing potential biomarkers of gut dysbiosis and circadian dysregulation. The identification of new biomarkers associated with the microbiota-gut-brain axis and circadian rhythmicity may help in early diagnosis and development of targeted therapies for mitigating neurodegenerative AD.
阿尔茨海默病（AD）是一种主要影响老年人群的严重破坏性神经退行性疾病。新出现的研究预示着肠道微生物群失调和昼夜节律紊乱与AD的早期发病有关。肠道微生物群失调的特征是肠道微生物群特征失调和肠道完整性受损，这会促使细菌代谢产物转移到体循环中。值得注意的是，源自肠道的代谢产物如钙卫蛋白、氧化三甲胺、犬尿氨酸、异戊胺和短链脂肪酸在AD发病机制中起关键作用。昼夜节律失调也通过积累β淀粉样蛋白（Aβ）和tau蛋白而与AD发病机制的加剧相对应。此外，昼夜节律失调是肠道微生物群失调的致病因素之一。本综述讨论了微生物群-肠道-脑轴、昼夜节律与AD发生之间的复杂相互作用。我们回顾了关于AD的临床前和临床研究，这些研究描述了肠道微生物群失调和昼夜节律失调的潜在生物标志物。识别与微生物群-肠道-脑轴和昼夜节律相关的新生物标志物可能有助于早期诊断和开发针对性疗法，以减轻神经退行性AD。
