Evidence links gut microbiome changes to Alzheimer’s progression

A sweeping review of human studies finds recurring gut microbiome changes across MCI and Alzheimer’s disease, while underscoring why inconsistent methods and short follow-up still limit firm conclusions.

Study: The microbiota–gut–brain axis in mild cognitive impairment and Alzheimer’s disease: a scoping review of human studies. Image Credit: Only_NewPhoto / Shutterstock

In a recent study published in the journal Alzheimer’s & Dementia, a group of researchers evaluated human evidence examining how alterations in the gut microbiome are associated with mild cognitive impairment (MCI) and Alzheimer’s disease (AD).

Alzheimer’s Disease Burden and Emerging Pathways

Alzheimer’s disease affects nearly 50 million people worldwide, with approximately 6.7 million cases in the United States alone, placing a substantial emotional and economic burden on families and healthcare systems. Alzheimer’s disease research has traditionally focused on genetics and brain pathology, but there is now growing interest in how the gut microbiome may influence immunity, metabolism, and brain signaling. Dysbiosis, defined as an imbalance in the microbiome environment, has been associated with brain inflammation and dysfunction.

According to various studies, changes in the gut microbiome may emerge before overt cognitive symptoms. As a result, lifestyle-based prevention and early detection strategies are increasingly being explored. Further studies are required to clarify causal relationships and therapeutic possibilities.

Scoping Review Design and Search Strategy

A scoping review methodology was applied using the five-stage framework proposed by Arksey and O’Malley and guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA–ScR) checklist. Researchers searched PubMed, Scopus, and the Cochrane Library up to February 2023 for studies examining the gut microbiome in individuals with MCI or AD. Eligible publications included original research articles, systematic reviews, and meta-analyses.

Study Selection and Data Extraction

Animal studies, non-English literature, and studies that did not directly evaluate gut microbiota composition were excluded. Multiple reviewers independently screened titles and abstracts, and studies meeting predefined inclusion and exclusion criteria were assessed at the full-text level.

Data were extracted on participant characteristics, microbiome assessment methods, cognitive outcomes, and key findings. Quantitative synthesis was not performed due to substantial methodological heterogeneity, including variation in sequencing techniques, dietary assessments, and cognitive testing. Instead, results were summarized narratively, highlighting recurrent microbial patterns, diversity metrics, and cognitive associations reported across observational and interventional studies.

Overview of Included Evidence

A total of 4,751 records were identified, of which 58 studies met the inclusion criteria after screening. These studies included case-control studies, randomized controlled trials, cohort studies, systematic reviews, and meta-analyses conducted across multiple countries, most frequently in China and Japan, as well as in Europe.

Gut Microbiome Patterns in Alzheimer’s Disease

Overall, the evidence indicated recurrent but heterogeneous differences in gut microbiota composition between individuals with MCI or AD and cognitively normal controls, with limited overlap in specific taxa reported across independent cohorts.

Several observational studies linked AD to gut dysbiosis, with many reporting reduced microbial diversity, although this finding was not universal. In contrast, alpha-diversity differences were less consistently observed in MCI. Individuals with AD were more frequently reported to have higher relative abundances of potentially pathogenic taxa such as Pseudomonadota and Actinomycetota.

Microbial Findings in Mild Cognitive Impairment

Findings in MCI were more variable. Some studies reported increased abundance of short-chain fatty acid-producing genera such as Faecalibacterium and Roseburia, while others observed reductions in these same taxa. These inconsistencies were often noted in small, population-specific studies, underscoring limited reproducibility across cohorts.

Species-Level Associations and Cognitive Status

At the species level, Escherichia coli was the only microorganism repeatedly identified as elevated across multiple AD studies, suggesting a potential role in inflammation or metabolic dysregulation. In contrast, fiber-fermenting and butyrate-producing genera such as Ruminococcus, Parabacteroides, and Butyricicoccus were more frequently reported in cognitively healthy controls, although these associations were inconsistent across studies.

Probiotics and Cognitive Outcomes

Studies examining probiotic interventions, primarily involving Lactobacillus and Bifidobacterium strains, showed mixed cognitive outcomes in MCI and AD populations. Some trials reported improvements in memory, attention, executive function, or slower rates of grey matter loss, whereas others found no significant cognitive benefit. Reported effects appeared to depend on strain specificity, dosage, and duration of treatment.

Diet, Lifestyle, and Microbiome Modulation

Dietary interventions, including Mediterranean-style and ketogenic-modified diets, were associated with alterations in gut microbiome composition that may be relevant to cognitive health. However, these findings were often derived from small or short-term studies and should be interpreted as associative rather than preventive evidence. Similarly, mindfulness-based interventions were linked to correlations between specific microbial taxa and cognitive performance, rather than definitive evidence of causal gut–brain mechanisms.

Interpretation and Research Gaps

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. 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. Further well-designed human studies and long-term intervention trials are required to determine whether targeting the gut microbiome can meaningfully alter the trajectory of cognitive aging and Alzheimer’s disease.