The association between gut microbiota and cognitive decline: A systematic review of the literature

Abstract

The gut-brain axis has emerged as a key pathway in the pathogenesis of neurodegenerative disorders, with age-related shifts in gut microbiota potentially contributing to cognitive decline and dementia progression. This systematic review evaluated the effects of microbiota-targeted interventions on cognitive outcomes in adults aged >45 years with cognitive impairment or at risk of dementia. Randomized controlled trials and quasi-experimental studies published up to June 2025 were identified through PubMed, COCHRANE, CINAHL, Web of Science, and EMBASE. Methodological quality, assessed using the Joanna Briggs Institute Critical Appraisal Checklist, ranged from moderate to high.Fifteen studies involving 4,275 participants across Europe, Asia, North America, and the Middle East met inclusion criteria. Interventions included probiotic supplementation, fecal microbiota transplantation, and dietary strategies such as Mediterranean and ketogenic diets. Cognitive outcomes were measured using validated tools, including the Mini-Mental State Examination, Montreal Cognitive Assessment, and Repeatable Battery for the Assessment of Neuropsychological Status. Narrative synthesis indicated that microbiota modulation was associated with improvements in memory, executive function, and global cognition, particularly in individuals with prodromal or mild cognitive impairment. Reported benefits correlated with increased microbial diversity, enhanced short-chain fatty acid production, and reduced neuroinflammatory markers. In contrast, effects were limited in advanced Alzheimer's disease.Overall, gut microbiota modulation represents a promising nonpharmacological strategy to support cognitive health, with early intervention appearing crucial for optimal benefit. Nevertheless, heterogeneity in study design and intervention protocols highlights the need for large-scale, longitudinal randomized controlled trials to confirm efficacy and clarify underlying biological mechanisms.