Importance of Gut Microbiota Dysbiosis and Circadian Disruption-Associated Biomarkers in Emergence of Alzheimer's Disease

Abstract

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.

Keywords: Alzheimer’s disease; Biomarkers; Circadian disruption; Gut dysbiosis; Gut-brain axis.