Gut Microbiome Features of Chinese Patients Newly Diagnosed with Alzheimer’s Disease or Mild Cognitive Impairment Original paper

What was studied?

This original study examined gut microbiome alterations in newly diagnosed Chinese patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI). The research assessed whether specific microbial signatures—including the focus keyphrase “gut microbiome dysbiosis in AD and MCI”—distinguish healthy aging from early cognitive decline. Importantly, all participants were treatment-naïve, enabling a clearer view of disease-linked microbial shifts not confounded by acetylcholinesterase inhibitors or other interventions. Fecal samples were collected and analyzed using 16S rRNA sequencing to characterize α- and β-diversity patterns, taxonomic composition across phylum, genus, and species levels, and correlations between microbial abundances and cognitive performance measured by MMSE, MoCA, and ADAS-Cog scores. Figures within the paper visually reinforced these shifts, such as the genus-level abundance bar charts and the LDA-based differential taxa plots.

Who was studied?

The study included 56 adults aged 60 years or older: 18 with newly diagnosed AD, 20 with MCI, and 18 cognitively normal controls. Participants were recruited from Sun Yat-sen Memorial Hospital clinics between 2018 and 2019. None had prior diagnoses of AD or MCI, nor had they taken antibiotics, glucocorticoids, or dementia-related medications. Groups were matched for age, BMI, and cardiometabolic comorbidities. Cognitive testing confirmed distinct impairment levels, with AD participants showing significantly lower MMSE and MoCA scores than those with MCI and controls. Exclusion criteria minimized confounders such as neurodegenerative diseases, psychiatric illness, intestinal disorders, and metabolic abnormalities, creating a relatively clean clinical background for microbiome evaluation.

Most important findings

Patients with AD and MCI exhibited significantly altered gut microbial profiles compared with controls, despite similar α-diversity. β-diversity measures, particularly Bray-Curtis and weighted UniFrac, demonstrated clear separation between controls and cognitively impaired groups. Prevotella 9 was consistently elevated in AD, with a similar—but nonsignificant—trend in MCI. Conversely, Bacteroides, Lachnospira, and Ruminiclostridium 9 were reduced in AD, with MCI showing milder decreases; Lachnospira reached significance in MCI. The Prevotella/Bacteroides ratio increased progressively from controls to MCI to AD, suggesting potential biomarker utility. Species-level data showed reduced Bacteroides fragilis and increased Prevotella 9 uncultured species in AD. Cognitive scores correlated positively with Bacteroides, Lachnospira, and Ruminiclostridium 9, and negatively with Prevotella 9 and the Prevotella/Bacteroides ratio , reinforcing functional relevance.

Key implications

The findings support a continuum of gut microbiome dysregulation from healthy aging to MCI to AD, characterized by loss of potentially protective taxa and expansion of genera associated with inflammation. Prevotella enrichment may amplify neuroinflammatory pathways, while reduced short-chain-fatty-acid–producing taxa (e.g., Ruminiclostridium 9) may lessen neuroprotection. The clear microbial gradient from MCI to AD suggests potential applications in early detection, prognosis, and therapeutic modulation, although the authors emphasize that causality remains unresolved.

Citation

Guo M, Peng J, Huang X, Xia L, Huang F, Zuo Z. Gut microbiome features of Chinese patients newly diagnosed with Alzheimer’s disease or mild cognitive impairment. Journal of Alzheimer’s Disease. 2021;80(1):299-310. doi:10.3233/JAD-201040