Mild cognitive impairment has similar alterations as Alzheimer’s disease in gut microbiota Original paper

What was studied?

This study investigated gut microbiota alterations in mild cognitive impairment (MCI) and Alzheimer’s disease (AD), with a specific focus on gut microbiota alterations in MCI and AD as potential early biomarkers for neurodegeneration. Using 16S rRNA gene sequencing of fecal and blood samples, the researchers compared microbial diversity, taxonomic composition, and functional pathways across individuals with AD, MCI, and healthy controls. They aimed to determine whether MCI already exhibits AD-like microbial signatures, whether specific taxa correlate with cognitive measures or amyloid burden, and whether microbial profiles could aid early detection. The study also integrated predictive modeling and explored microbial metabolic pathways relevant to amyloid biology, inflammation, gut permeability, and neurodegeneration.

Who was studied?

Ninety participants were included: 30 with clinically diagnosed AD, 30 with MCI, and 30 cognitively normal controls. Groups were matched for age, sex, education, body mass index, and constipation history. AD diagnosis followed NIA-AA criteria and included symptomatic presentation with neuroimaging evidence. MCI participants had subjective memory complaints and mild temporal lobe atrophy but lacked functional impairment. None of the MCI or control participants were taking medications that significantly influence cognition or the microbiome, while AD participants commonly used acetylcholinesterase inhibitors or memantine. Dietary patterns were controlled to minimize confounding microbiome effects.

Most important findings

The study demonstrated that MCI shares strikingly similar gut and blood microbiota profiles with AD, indicating that dysbiosis arises before dementia onset. AD and MCI exhibited significantly reduced α-diversity—especially phylogenetic diversity—and distinct β-diversity patterns compared with controls. Eleven fecal genera differed between AD and controls after adjustment: elevated Lactobacillus, Bifidobacterium, Blautia, Dorea, Streptococcus, and Escherichia; reduced Bacteroides, Parabacteroides, Alistipes, Sutterella, and Paraprevotella. Blood microbiota also showed significant shifts, including increased Escherichia, Pseudomonas, and Propionibacterium. Escherichia emerged as a key genus elevated in both feces and blood of AD and MCI participants. Its known production of amyloid-like proteins and lipopolysaccharides aligns with observations of Escherichia-derived fragments colocalizing with amyloid plaques. Several Firmicutes genera (Blautia, Dorea) were associated with poorer cognition, while genera such as Faecalibacterium correlated with better cognitive scores. KEGG functional predictions indicated reductions in microbial genes involved in amino acid, carbohydrate, and lipid metabolism in AD. A random forest classifier identified 93% of MCI cases using fecal taxa profiles.

Key implications

This work shows that AD-like microbial dysbiosis is already present during MCI, indicating that gut microbiota shifts may precede clinical dementia by years. Elevated Escherichia, along with amyloidogenic and pro-inflammatory taxa, may influence amyloid deposition, blood–brain barrier permeability, and neuroinflammation, offering mechanistic links between the gut and brain. Reduced Bacteroides may weaken intestinal barrier integrity, increasing systemic inflammation. Microbial signatures may thus serve as noninvasive biomarkers for early AD detection, while microbial pathways offer potential therapeutic targets, including probiotic modulation, dietary interventions, and microbiome-directed diagnostics.

Citation

Li B, He Y, Ma J, et al. Mild cognitive impairment has similar alterations as Alzheimer’s disease in gut microbiota. Alzheimer’s & Dementia. 2019;1-10