Drug Development

Area of Science:

• Neuroscience
• Gastroenterology
• Microbiology

Background:

• The gut-brain axis significantly influences neurodegenerative diseases like Alzheimer's disease (AD).
• Fecal microbiota transplantation (FMT) is being explored as a therapeutic strategy for AD, aiming to rebalance gut microbes and reduce neuroinflammation.
• Current clinical evidence supporting FMT for AD is limited.

Purpose of the Study:

• To review the potential effects of FMT on cognitive function in patients with Alzheimer's disease (AD) and other cognitive disorders.
• To synthesize existing clinical evidence on FMT's efficacy in improving cognition.

Main Methods:

• A systematic literature search was conducted across PubMed, Cochrane, Scopus, and Embase for human studies on FMT and cognition in AD.
• Eligible studies included clinical trials, case series, and case reports; reviews, editorials, animal, and non-English studies were excluded.
• Data extraction and quality assessment were performed by multiple reviewers; meta-analysis was not feasible due to study heterogeneity.

Main Results:

• Five studies involving 26 dementia patients (all with recurrent Clostridium difficile infection) were analyzed.
• Fecal microbiota transplantation (FMT) was associated with cognitive improvements, particularly in mild cognitive impairment and AD patients.
• A randomized controlled trial showed significant improvements in MMSE and CDR-SOB scores post-FMT. Observational studies reported enhanced cognitive scores, mood, and daily activity performance. Microbiome analysis revealed shifts correlating with reduced neuroinflammation and metabolic improvements. Adverse effects were minor and transient.

Conclusions:

• Preliminary findings suggest that FMT may offer cognitive benefits for individuals with Alzheimer's disease (AD) and recurrent Clostridium difficile infection (CDI).
• The current evidence base is limited by the small number of studies and the frequent co-occurrence of CDI.
• Larger, well-controlled clinical trials are essential to validate FMT's therapeutic role in AD management.