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

Fifteen studies involving 4,275 participants met inclusion criteria for this systematic review of microbiota-targeted interventions and cognitive outcomes.

• Participants were adults aged >45 years with cognitive impairment or at risk of dementia.
• Studies were drawn from Europe, Asia, North America, and the Middle East.
• Randomized controlled trials and quasi-experimental studies published up to June 2025 were included.
• Databases searched included PubMed, COCHRANE, CINAHL, Web of Science, and EMBASE.
• Methodological quality assessed using the Joanna Briggs Institute Critical Appraisal Checklist ranged from moderate to high.

Microbiota-targeted interventions were associated with improvements in memory, executive function, and global cognition.

• Improvements were particularly observed in individuals with prodromal or mild cognitive impairment.
• 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 was used as the method of evidence combination.
• Effects were limited in advanced Alzheimer's disease.

Three categories of microbiota-targeted interventions were evaluated: probiotic supplementation, fecal microbiota transplantation, and dietary strategies.

• Dietary strategies included Mediterranean and ketogenic diets.
• Reported benefits correlated with increased microbial diversity.
• Benefits also correlated with enhanced short-chain fatty acid production.
• Reduced neuroinflammatory markers were associated with reported cognitive benefits.

Early intervention with microbiota modulation appeared crucial for optimal cognitive benefit.

• Effects were most pronounced in individuals with prodromal or mild cognitive impairment.
• In contrast, effects were limited in advanced Alzheimer's disease.
• The gut-brain axis was identified as a key pathway in the pathogenesis of neurodegenerative disorders.
• Age-related shifts in gut microbiota were described as potentially contributing to cognitive decline and dementia progression.

Heterogeneity in study design and intervention protocols was identified as a key limitation necessitating further research.

• The authors called for large-scale, longitudinal randomized controlled trials to confirm efficacy.
• Such trials were also needed to clarify underlying biological mechanisms.
• Study designs included both randomized controlled trials and quasi-experimental studies, contributing to heterogeneity.
• Interventions varied across probiotic supplementation, fecal microbiota transplantation, and dietary approaches.