A new review published in Alzheimer's & Dementia has found recurring changes in the gut microbiome among people with mild cognitive impairment (MCI) and Alzheimer’s disease (AD), but also highlights significant limitations in current research methods and study durations.
Alzheimer’s disease affects about 50 million people globally, including roughly 6.7 million in the United States. This creates a major burden for families and healthcare systems. While much research has focused on genetics and brain pathology, there is growing interest in how the gut microbiome may affect immunity, metabolism, and brain signaling. An imbalance in the gut microbiome, known as dysbiosis, has been linked to brain inflammation and dysfunction.
Some studies suggest that changes in the gut microbiome may occur before clear cognitive symptoms appear. This has led researchers to consider prevention strategies based on lifestyle factors and early detection. However, more research is needed to clarify whether these changes cause cognitive decline or are simply associated with it.
The review used a scoping methodology based on established frameworks to search PubMed, Scopus, and the Cochrane Library for relevant studies up to February 2023. Only original research articles, systematic reviews, and meta-analyses focusing on humans were included; animal studies and non-English literature were excluded.
After screening 4,751 records, 58 studies met inclusion criteria. These included case-control studies, randomized controlled trials, cohort studies, systematic reviews, and meta-analyses from various countries—most often China and Japan.
The evidence showed repeated but varied differences in gut microbiota between people with MCI or AD compared to cognitively healthy controls. There was limited agreement across different cohorts regarding which specific bacteria were involved.
Several observational studies linked AD to reduced microbial diversity—a finding not always seen across all groups studied. People with AD were more likely to have higher levels of certain potentially harmful bacteria such as Pseudomonadota and Actinomycetota.
Results for MCI were less consistent: some studies reported increases while others saw decreases in short-chain fatty acid-producing genera like Faecalibacterium and Roseburia. These inconsistencies were often observed in small or population-specific samples.
At the species level, Escherichia coli was repeatedly found at higher levels among those with AD across multiple studies. In contrast, bacteria such as Ruminococcus, Parabacteroides, and Butyricicoccus—known for fermenting fiber—were more common among healthy controls but not consistently so across all reports.
Probiotic interventions using Lactobacillus and Bifidobacterium strains produced mixed results regarding memory improvement or slower loss of grey matter; outcomes appeared dependent on strain type, dosage amount, and treatment duration.
Dietary approaches like Mediterranean-style or ketogenic-modified diets changed gut microbiome composition but did not provide preventive evidence due to their small scale or short duration. Mindfulness-based interventions showed correlations between certain microbes and cognitive performance rather than direct proof of a causal relationship between gut health and brain function.
According to the authors: "Human evidence increasingly supports an association between gut microbiome alterations and cognitive decline across the Alzheimer’s disease spectrum. Changes in microbial diversity and composition appear to occur in subsets of individuals during early MCI and persist throughout AD progression, potentially influencing neuroinflammatory pathways and brain health."
They added: "Because the gut microbiome is modifiable through diet, probiotics, and lifestyle factors, these findings raise theoretical opportunities for risk modification."
However: "Substantial methodological variability, limited longitudinal data, and a predominant focus on microbial composition rather than functional or metabolic profiling preclude causal inference." The authors conclude that further well-designed human studies are necessary to determine if targeting the gut microbiome can impact cognitive aging or Alzheimer’s progression.
