Gut Microbiome Alterations in Mild Cognitive Impairment: Findings from the ALBION Greek Cohort

Study information

Needs review

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

41011443

DOI Digital object identifier for electronic documents.

https://doi.org/10.3390/microorganisms13092112

URI Uniform resource identifier for web resources.

https://www.mdpi.com/2076-2607/13/9/2112#app1-microorganisms-13-02112

Authors

Rouskas K., Mamalaki E., Ntanasi E., Pantoura M., Anezaki M., Emmanouil C., Novau-Ferré N., Bulló M., Dimas A.S., Papandreou C., Yannakoulia M., Argiriou A., Scarmeas N.

Journal

Microorganisms

Year

2025

Keywords:

Alzheimer’s disease, discrimination model, gut microbiota, microbiome, microbiota-gut–brain axis, mild cognitive impairment

Emerging evidence suggests a potential role of gut dysbiosis in neurodegenerative disorders and, in particular, Alzheimer's disease (AD) pathology and cognitive decline. However, the role of gut microbiome in the early prodromal stages of AD and particularly in mild cognitive impairment (MCI) remains understudied and has been mostly explored in Asian populations with no representation of European populations. To address this research gap in the literature and to suggest novel microbiome features associated with MCI, we conducted a cross-sectional study in a European population sample and profiled gut microbiota in 99 individuals without dementia through 16s ribosomal RNA (rRNA) sequencing. Individuals were categorized by cognitive status based on standard clinical criteria to cognitively normal (n = 49) or individuals with MCI (n = 50). Differential abundance through Microbiome Multivariable Associations with Linear model (MaAsLin2) and elastic net logistic regression analyses were used to identify gut microbiome features associated with MCI. MCI group was older than the CN group and age was used as covariate in the differential abundance analysis. No differences in alpha and beta diversity were found between the two groups (p > 0.05). At false discovery rate (FDR) < 0.05, we identified specific genera associated with MCI, mostly linked to short chain fatty acids (SCFAs) production (e.g., Candidatus_Soleaferrea q = 0.027, MaAsLin2 coefficient = 1.65, Sellimonas q = 0.017, MaAsLin2 coefficient = -4.45), while we highlight nominal (p < 0.05, q > 0.05) correlations of genera (e.g., Hydrogenoanaerobacterium, Subdoligranulum) with metrics of cognitive assessment. Microbiota was shown to have a fairly good discriminative capacity for MCI status (area under the curve AUC = 0.77), with Rothia genus found as the top predictor for MCI (beta coefficient [95% confidence intervals] = 0.224 [0.216-0.233]). Overall, our findings add to current knowledge reporting gut microbiome alterations in MCI by suggesting novel associated microbiome features; however, larger scale longitudinal studies are needed to further elucidate the underlying biological pathways linked to the disease.

Experiment 1

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Needs review

Curated date: 2025/10/13

Curator: Kimbrene Kakande

Revision editor(s): Kimbrene Kakande, Temmie, Fiddyhamma

Subjects

Location of subjects: Greece

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Cognitive impairment Abnormality of cognition,Cognitive abnormality,Cognitive defects,Cognitive deficits,Cognitive impairment,Intellectual impairment,cognitive impairment

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Cognitively Normal (CN)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Mild Cognitive Impairment (MCI)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Milld cognitive impairment (MCI) Is an early prodromal stage of Alzheimer disease (AD)

Group 0 sample size Number of subjects in the control (unexposed) group: 49

Group 1 sample size Number of subjects in the case (exposed) group: 50

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 3 months

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: log transformation

Statistical test: MaAsLin2

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, sex, Confounders controlled for: "MMSE" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.MMSE, Confounders controlled for: "sequencing platform" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.sequencing platform, Confounders controlled for: "medical history of hypertension" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.medical history of hypertension

Alpha Diversity

Pielou Quantifies how equal the community is numerically: unchanged

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa: unchanged

Richness Number of species: unchanged

Signature 1

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Curated date: 2025/10/17

Curator: Fiddyhamma

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Source: Figure 3A and Table S2

Description: Differentially abundant genera between the cognitively normal and individuals with MCI. Volcano plots display −log10 adjusted p-values and log2 fold changes for (A) genera between the two groups. Significant changes are highlighted in blue (increased at MCI) or yellow (decreased at MCI) color

Abundance in Group 1: increased abundance in Mild Cognitive Impairment (MCI)

NCBI	Quality Control	Links
Candidatus Soleaferrea
Hydrogenoanaerobacterium
UBA1819UBA1819

Revision editor(s): Fiddyhamma

Signature 2

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Mark reviewed

Your review change was submitted

Needs review

Curated date: 2025/10/17

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Source: Figure 3A and Table S2

Description: Differentially abundant genera between the cognitively normal and individuals with MCI. Volcano plots display −log10 adjusted p-values and log2 fold changes for (A) genera between the two groups. Significant changes are highlighted in blue (increased at MCI) or yellow (decreased at MCI) color

Abundance in Group 1: decreased abundance in Mild Cognitive Impairment (MCI)

NCBI	Quality Control	Links
Barnesiella
Eisenbergiella
Sellimonas
Subdoligranulum
UCG_011UCG_011
CAG_352CAG_352

Revision editor(s): Fiddyhamma