Gut Microbiota is Altered in Patients with Alzheimer’s Disease Original paper

What was studied?

This original research article examined gut microbiome alterations in Alzheimer’s disease (AD), focusing on how changes in microbial composition might relate to the disease’s pathophysiology. The study used 16S rRNA sequencing to compare fecal microbiomes from AD patients and cognitively normal controls, with particular attention to taxa that differed significantly between groups. This analysis of gut microbiome signatures revealed reduced Bacteroidetes and increased Actinobacteria and Ruminococcaceae in AD, suggesting microbial dysbiosis that could influence neuroinflammation, intestinal permeability, and amyloid-related processes. These findings contribute to a broader understanding of how gut microbiome changes may shape systemic and neurological pathways relevant to AD.

Who was studied?

The study included 43 patients diagnosed with Alzheimer’s disease and 43 age- and gender-matched cognitively healthy controls. Participants were recruited from multiple hospitals in Chongqing, China, and underwent extensive clinical evaluation, including MMSE, CDR, and ADL assessments. Individuals with confounding conditions—such as recent antibiotic use, neurodegenerative disorders, psychiatric illness, severe organ disease, or gastrointestinal disorders—were excluded to limit extraneous effects on gut microbiota. A subset of 12 participants also underwent amyloid PET imaging to confirm amyloid deposition. Both groups shared similar lifestyle and dietary backgrounds, strengthening the study’s internal validity regarding microbiome comparisons.

Most important findings

The study showed distinct gut microbial signatures differentiating AD patients from controls across phylum, class, family, and genus levels. At the phylum level, Bacteroidetes were significantly decreased, while Actinobacteria were increased in AD. Family-level differences were pronounced: the AD group had higher Ruminococcaceae, Enterococcaceae, and Lactobacillaceae and lower Lachnospiraceae, Bacteroidaceae, and Veillonellaceae. LEfSe analysis highlighted several discriminatory taxa, including reduced Negativicutes and diminished Bacteroidia. Increased Ruminococcus—a mucus-degrading genus associated with altered metabolites such as N-acetylaspartate—suggests possible microbiome–brain metabolic interactions. The Firmicutes/Bacteroidetes ratio, elevated in AD, aligned with patterns seen in metabolic dysfunction. The study’s data, including PLS-DA plots, depict clear microbial clustering separating AD from controls, supporting robust compositional divergence.

Key implications

These findings reinforce the concept that the gut microbiome may participate in Alzheimer’s disease pathogenesis through metabolic, immunological, and neuroinflammatory pathways. Reduced Bacteroides aligns with previous studies linking this group to cognitive impairment and amyloid biology, while increased Actinobacteria and Ruminococcaceae may contribute to gut barrier dysfunction and inflammatory signaling. The possibility that bacterial metabolites, inflammatory mediators, or even bacterial components could influence amyloid production or tau phosphorylation expands the understanding of AD beyond a solely brain-based disorder. This work supports future exploration of microbiome-targeted interventions—dietary modulation, probiotics, or microbial therapeutics—in AD prevention or management, and provides foundational microbial signatures relevant to clinical decision-making and biomarker development.

Citation

Zhuang ZQ, Shen LL, Li WW, et al. Gut microbiome is altered in patients with Alzheimer’s disease.Journal of Alzheimer’s Disease. 2018;10.3233/JAD-180176. zhuang2018