**Background:** Alzheimer’s disease (AD) is the most common form of dementia, affecting over 50 million people worldwide, with prevalence shifting from high-income to middle- and low-income countries (projected 63% of cases by 2030 and 71% by 2050). Despite extensive research, no preventative or curative therapy exists. Emerging evidence suggests that the gut microbiota differs between AD patients and cognitively normal individuals, and that diet—a strong modulator of gut microbiota—may influence AD pathology through the gut-brain axis. This narrative review synthesizes current knowledge on the diet-microbiota-brain axis in AD, focusing on how nutritional approaches could offer novel preventive and therapeutic strategies.
**Methods:** This is a narrative review that summarizes findings from human and animal studies, as well as clinical trials, examining the links between diet, gut microbiota, and AD. The authors discuss pathophysiological mechanisms (e.g., amyloid-beta plaques, tau tangles, inflammation, oxidative stress), the role of gut microbiota metabolites (e.g., short-chain fatty acids, trimethylamine N-oxide, lipopolysaccharide), and dietary interventions (e.g., Mediterranean diet, MIND diet, probiotics, synbiotics). No systematic search strategy or meta-analysis was performed; the review is based on selected references (1–36).
**Key Results:** The review reports that AD patients exhibit distinct gut microbiota patterns, including lower Bacteroidetes and higher Firmicutes and Proteobacteria in mild cognitive impairment (MCI) patients, and lower diversity and lower Firmicutes-to-Bacteroidetes ratio in AD subjects. Gut microbiota-derived trimethylamine N-oxide (TMAO) is elevated in cerebrospinal fluid of MCI/AD patients and correlates with AD biomarkers (pTau, total Tau, Aβ42). TMAO treatment in mice reduces cognitive function and increases neuronal senescence and mitochondrial dysfunction. Lipopolysaccharide (LPS) from Gram-negative bacteria enhances Aβ accumulation and induces cognitive dysfunction; AD patients show higher LPS levels in blood plasma and brain regions (neocortex, hippocampus). Dietary interventions show promise: the Mediterranean diet correlates with less brain atrophy in key AD areas and decreased inflammation (increased plasma carotenoids, decreased C-reactive protein). The MIND diet (Mediterranean-DASH Intervention for Neurodegenerative Delay) was more effective than either diet alone in reducing AD pathology. A 12-week randomized controlled trial of a probiotic combination (Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, Lactobacillus fermentum) in AD patients reported significant positive effects on cognitive functioning, though no effects on oxidative stress or inflammation. A mouse study found that 12 weeks of sodium butyrate supplementation significantly reduced Aβ levels and improved behavioral responses. A human study using kefir-fermented milk (synbiotic) for 90 days showed improved mental capabilities and reduced inflammation and oxidative stress in AD patients. Additionally, the drug trazodone was associated with delaying cognitive impairment 2.6 times more than non-users.
**Clinical Implications:** The review underscores that dietary patterns rich in vegetables, fruits, whole grains, polyunsaturated fatty acids, and probiotics/prebiotics may help prevent or slow AD progression by modulating gut microbiota, reducing inflammation, and improving metabolic health. Conversely, Western diets high in saturated fats, simple sugars, and processed meats may exacerbate AD risk. The gut-brain axis emerges as a critical pathway, with gut microbiota metabolites (SCFAs, TMAO, LPS) influencing neuroinflammation, amyloidosis, and oxidative stress. While the evidence is promising, the authors note that most studies are cross-sectional, and more longitudinal intervention trials are needed to establish causal links. Targeting the gut microbiota through diet or supplementation (probiotics, synbiotics, postbiotics) represents a novel, modifiable approach for AD prevention and management, but further research is required to translate these findings into clinical practice.