A new review traces how diet, gut bacteria, and their metabolites may intersect with the silent biological changes that precede cognitive decline.

Review: Gut Microbiome Changes in Preclinical Alzheimer’s Disease. Image Credit: Toey Andante / Shutterstock

In a recent narrative review published in the journal Nutrients, researchers across Australia summarized evidence on the gut microbiota, microbial metabolites, and dietary patterns in relation to early Alzheimer’s disease (AD). The review did not generate or analyze new data.

AD has a long preclinical stage when metabolic alterations, amyloid accumulation, and neuroinflammation develop while people remain cognitively unimpaired (CU). Understanding these biological changes can help elucidate mechanisms pertinent to early prevention. Recent findings suggest that early AD pathology may be accompanied by alterations in the gut microbiota and other systemic changes. Diet plays an important role in gut microbiota composition and metabolic output.

Diet-induced changes in the microbiota may influence gut–brain communication relevant to metabolic and neuroinflammatory regulation. Research also links long-term dietary patterns to the risk of cognitive impairment and AD. Nevertheless, the relevance of microbiome–diet interactions to microbial functional pathways in preclinical AD remains poorly defined. In this narrative review, researchers summarized evidence linking the gut microbiota, microbial metabolites, and diet to early AD.

Expected growth in the number of people living with dementia globally and in Australia. (A) Estimated global increase in the number of people living with dementia from 2020 to 2050. (B) Estimated increase in the number of people living with dementia in Australia over the same period.

AD: Diagnosis and Therapeutic Context

Research advances have enabled AD detection based on biological markers without relying solely on clinical symptoms. Cerebrospinal fluid (CSF) biomarkers and amyloid positron emission tomography (PET) imaging enable the detection of pathology in CU individuals. Standardized amyloid PET quantification, such as the Centiloid scale, can help stratify people along the preclinical continuum and facilitate comparisons across studies.

Current AD treatments offer limited benefit once cognitive decline is established. Common symptomatic treatments, including memantine, donepezil, galantamine, and rivastigmine, provide modest cognitive and functional improvements. Further, while disease-modifying therapies, for example, lecanemab, have been developed for early-stage AD, they are restricted to select populations and have limited clinical benefit.

As such, most available treatments are initiated only after substantial damage has occurred, thereby reducing their capacity to meaningfully modify disease progression. This therapeutic limitation constitutes a substantial challenge in AD treatment, underscoring the need for further research and attention toward earlier AD stages.

Gut–Brain Communication

The gut–brain axis (GBA) is the bidirectional communication network between the central nervous system (CNS) and the gastrointestinal system. It plays an important role in regulating physiological processes, including brain function, metabolism, and immune activity. Alterations in the microbiota composition can modify metabolic and inflammatory conditions in ways that may increase vulnerability to neurodegenerative processes.

Microbial metabolites are an important component of gut–brain communication. Short-chain fatty acids (SCFAs), the most studied metabolites, regulate immune cell differentiation, metabolic pathways, epithelial barrier integrity, and cytokine production. SCFAs can modulate neuronal function and neuroinflammatory processes through these actions. Emerging evidence suggests that GBA disruptions may contribute to the metabolic and inflammatory disturbances seen in early AD. However, direct human evidence in preclinical AD remains limited, and SCFA effects may depend on their concentration and biological context.

Gut Microbiome Dysregulation in AD

A growing body of research suggests that AD is associated with changes in gut microbiota function and composition. In particular, reduced abundance of SCFA-producing genera, such as Eubacterium, Roseburia, and Faecalibacterium, has been commonly reported in AD and cognitive impairment. Meanwhile, some studies report an increased relative abundance of Escherichia/Shigella and other Proteobacteria, which are associated with inflammatory signaling, metabolic imbalance, and oxidative stress.

Microbiota functional alterations in AD include disruptions in fermentation pathways, changes in lipid and amino acid metabolism, and decreases in SCFA biosynthesis. Early changes in microbial metabolic pathways and SCFA-producing taxa have been reported in a small number of studies involving CU individuals with biomarker evidence of amyloid pathology. Although studies have reported inconsistent findings, they suggest that the earliest stages of AD may be characterized by gut microbial dysregulation.

Dietary Patterns Associated With AD

Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet (MD) are associated with improved cognitive, cardiovascular, and metabolic outcomes in aging populations. Both emphasize increased intake of plant-based foods, while limiting processed and red meats, added sugars, and saturated fats. Higher adherence to these diets is linked to reduced cerebral amyloid burden, slower cognitive decline, and improved vascular function in older individuals.

The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, which combines elements from DASH and MD, has similarly been associated with slower accumulation of AD-related pathology. Further, the prudent dietary pattern has been associated with improved inflammatory and metabolic profiles in aging populations. It is characterized by high intake of fruits, whole grains, vegetables, fish, low-fat dairy, and legumes. The prudent dietary pattern has been associated with higher microbial diversity and enrichment of SCFA-producing taxa.

Concluding Remarks

Collectively, available research suggests that alterations in the composition and metabolic activity of the gut microbiota may be associated with early AD pathology. Reductions in SCFA-producing taxa and alterations in microbial metabolic pathways have been observed in a limited number of studies involving CU populations with amyloid pathology.

However, the current evidence base has important limitations. Most studies have involved populations with AD or mild cognitive impairment rather than biomarker-confirmed preclinical AD, and much of the available evidence is cross-sectional, preventing conclusions about the direction of the relationship. Sequencing has generally been limited to the genus level, while few studies have jointly assessed diet, gut microbiota, microbial functional pathways, SCFAs, and amyloid pathology. As a narrative review, this work also focused primarily on SCFAs rather than other potentially relevant microbial metabolites.

Future studies should prioritize longitudinal, species-level metagenomic analyses in CU individuals grouped by amyloid status. These studies should assess microbial functional pathways, SCFAs, and diet within the same cohort. Researchers should also investigate fecal microbiota transplantation as a potential intervention in experimental AD models.

Journal reference:

• Dissanayaka DMS, Rainey-Smith SR, Sohrabi HR, et al.(2026). Gut Microbiome Changes in Preclinical Alzheimer’s Disease. Nutrients, 18(15):2469.DOI:10.3390/nu18152469. https://www.mdpi.com/2072-6643/18/15/2469