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

What was studied?

The focus keyphrase, gut microbiota in mild cognitive impairment, is central to this study, which investigated whether individuals with mild cognitive impairment (MCI) display gut microbiota alterations similar to those observed in Alzheimer’s disease (AD). The authors analyzed fecal and blood microbiota using 16S rRNA sequencing to determine whether microbial signatures that characterize AD are already detectable during the prodromal MCI stage. The study was built on the rationale that gut-derived inflammatory and amyloidogenic signals may contribute to neurodegenerative processes through the gut–brain axis and that early dysbiosis might serve as an accessible biomarker for preclinical disease.

Who was studied?

Ninety participants were enrolled: 30 with AD, 30 with MCI, and 30 cognitively normal controls. All groups were similar in age, sex distribution, BMI, education, constipation frequency, and comorbidities. AD participants had significantly lower cognitive scores and longer symptom duration, while MCI participants showed mild impairment without functional loss. Fecal and blood samples were collected from all subjects, and sequencing depth exceeded 3.9 million reads. The inclusion criteria followed NIA-AA diagnostic guidelines, and dietary patterns were controlled to minimize confounding.

Most important findings

AD and MCI exhibited nearly identical microbial alterations. Diversity analyses demonstrated reduced alpha-diversity in AD fecal and blood microbiota, with MCI showing a similar but statistically indistinguishable pattern. Beta-diversity separations were pronounced between controls and both clinical groups. Key taxonomic shifts were virtually the same in AD and MCI, with differential genera illustrated on LDA plots. Several genera increased in both AD and MCI, notably Escherichia, Lactobacillus, Bifidobacterium, Streptococcus, Dorea, and Blautia—many within the Firmicutes phylum. Genera decreased included Bacteroides, Alistipes, Parabacteroides, Sutterella, and other Bacteroidetes-associated taxa. E. coli elevation was confirmed in qPCR validation. Correlations on heatmaps showed that Akkermansia abundance corresponded with medial temporal atrophy, while taxa such as Blautia and Dorea were associated with lower MMSE scores. Predicted functional pathways revealed reduced microbial gene capacity for amino acid, carbohydrate, lipid, and vitamin metabolism in AD compared to controls. A diagnostic model using fecal genera accurate for AD also identified 93% of MCI subjects, supporting overlapping microbial signatures.

Key implications

These findings indicate that gut microbiota dysbiosis emerges during MCI, preceding clinical dementia and mirroring AD-associated microbial patterns. Elevated gram-negative taxa such as Escherichia may contribute to systemic inflammation and amyloidogenesis through lipopolysaccharide exposure and microbial amyloids; these mechanisms align with existing amyloid and inflammatory theories. Reduced Bacteroidetes genera may weaken intestinal barrier integrity, compounding neuroinflammatory risk. The near-complete overlap between AD and MCI signatures highlights the potential of gut microbiota as an early, noninvasive biomarker source and suggests that modulating dysbiosis (e.g., diet, probiotics) warrants further clinical investigation.

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. doi:10.1016/j.jalz.2019.07.002