Gut Microbiota Alterations and Their Impact on Alzheimer’s disease Progression: Review article

Background: Alzheimer’s disease (AD), a progressive neurodegenerative disorder, affects over 50 million people worldwide, causing significant cognitive decline and memory impairment. Emerging evidence suggests that the gut microbiota, through the gut-brain axis, plays a critical role in AD pathogenesis by modulating neuroinflammation, amyloid-beta (Aβ) deposition and tau pathology. Dysbiosis or microbial imbalance has been linked to exacerbated AD progression with studies reporting reduced microbial diversity and altered taxonomic profiles in AD patients. Objective: This literature review aimed to synthesize current evidence on gut microbiota alterations and their impact on AD progression, drawing from clinical, preclinical and mechanistic studies published between 2015 and 2024.
Methods: A systematic search was conducted using PubMed, Google Scholar, and Scopus, with keywords including “Gut microbiota”, “Alzheimer’s disease”, “Gut-brain axis”, “Neurodegeneration”, “Microbiome dysbiosis”, “Alzheimer’s progression” and “probiotics”. The writers evaluated relevant literature references as well. Documents written in languages other than English have been ignored. Papers that were not regarded as significant scientific research included dissertations, oral presentations, conference abstracts, and unpublished manuscripts were excluded.
Conclusion: Findings indicated that reduced Firmicutes, increased Bacteroidetes and decreased Bifidobacterium are common in AD, correlating with elevated biomarkers like Aβ42 and phosphorylated tau. Animal models and limited human trials suggest that microbial metabolites, such as short-chain fatty acids (SCFAs), influence neuroprotection, while dysbiosis promotes systemic inflammation. Therapeutic strategies, including probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), showed promise but lack large-scale validation. Challenges include variability in microbial profiles, small sample sizes, and inconsistent methodologies. This review highlights the gut microbiota as a potential therapeutic target for AD, advocating for standardized research protocols, longitudinal studies and robust clinical trials to establish causality and therapeutic efficacy.