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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Gut Microbiome Alterations in Alzheimer’s Disease: A Shotgun Metagenomic Case–Control Study

  • Argul Issilbayeva1,2
  • Samat Kozhakhmetov2
  • Almagul Kushugulova2
  • Sholpan Askarova3
  • Aiym Kaiyrlykyzy3
  • Dilyar Tuigunov4
  • Oksana Dolmatova4
  • Zhibek Zholdassova5
  • Yerzhan Omarov4
  • Talgat Nurgozhin4,6
6 affiliations
  1. 1Innovative Center ArtScience, Astana Z11F5A9, Kazakhstan
  2. 2Laboratory of Microbiome, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana Z05H0P9, Kazakhstan
  3. 3Laboratory of Bioengineering and Regenerative Medicine, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana Z05H0P9, Kazakhstan
  4. 4Laboratory of Food Biotechnology and Specialty Food Products, Kazakh Academy of Nutrition, Almaty A05D9M8, Kazakhstan
  5. 5Neurosis and Alzheimer’s Disease Treatment Center, Almaty A05E1P7, Kazakhstan
  6. 6School of General Medicine, Asfendiyarov Kazakh National Medical University, Almaty A05H2A6, Kazakhstan
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Abstract

The gut microbiome has been proposed as a contributor to Alzheimer’s disease (AD) pathogenesis via the microbiota–gut–brain axis, but findings across cohorts are inconsistent and scarce data exist from Central Asian populations. We used shotgun metagenomic sequencing to compare the gut microbiome of AD patients and cognitively healthy controls from Kazakhstan. In a cross-sectional case–control study (35 AD, 39 Control), we profiled taxonomic and functional (HUMAnN pathway) composition, and compared alpha/beta diversity, individual taxa and pathways, and their association with clinical and demographic variables (Mann–Whitney U test, PERMANOVA/PERMDISP, OLS regression, all BH-FDR corrected, sensitivity analysis using ANCOM-BC2), with sensitivity analyses adjusting for age and BMI and applying Bonferroni correction. Within the AD group, circulating adiponectin—measured only in this group—was examined for associations with microbiome features in an exploratory analysis. Alpha diversity was lower in AD (q < 0.05). Community composition also separated by group on PERMANOVA (R2 = 8.6%, p = 0.001), and this separation held after adjusting for age and BMI. A total of 178 taxa differed significantly between groups (BH-FDR; 37 were also Bonferroni-significant), most prominently depletion of Faecalibacterium and enrichment of Eisenbergiella and Desulfovibrio in AD; 100 pathways differed significantly (20 Bonferroni-significant). Three clinical/demographic variables (total bilirubin, atherogenic index, BMI) were associated with specific taxa or pathways. Within the AD group, adiponectin correlated negatively with the pathway assimilatory sulfate reduction IV (rho = −0.60, q = 0.015). AD in this Central Asian cohort was associated with a less diverse, compositionally distinct gut microbiome, with depletion of butyrate-producing Firmicutes and enrichment of sulfate-reducing taxa, alongside other taxa whose direction of association differed from prior reports.

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Cite

BibTeXRIS
BibTeX
@article{issilbayeva2026microbiome,
  title = {{Gut Microbiome Alterations in Alzheimer’s Disease: A Shotgun Metagenomic Case–Control Study}},
  author = {Argul Issilbayeva and Samat Kozhakhmetov and Almagul Kushugulova and Sholpan Askarova and Aiym Kaiyrlykyzy and Dilyar Tuigunov and Oksana Dolmatova and Zhibek Zholdassova and Yerzhan Omarov and Talgat Nurgozhin},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27219543},
  url = {https://www.mdpi.com/1422-0067/27/21/9543},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Gut Microbiome Alterations in Alzheimer’s Disease: A Shotgun Metagenomic Case–Control Study
AU  - Argul Issilbayeva
AU  - Samat Kozhakhmetov
AU  - Almagul Kushugulova
AU  - Sholpan Askarova
AU  - Aiym Kaiyrlykyzy
AU  - Dilyar Tuigunov
AU  - Oksana Dolmatova
AU  - Zhibek Zholdassova
AU  - Yerzhan Omarov
AU  - Talgat Nurgozhin
PY  - 2026
DA  - 2026/10/25
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219543
UR  - https://www.mdpi.com/1422-0067/27/21/9543
AB  - The gut microbiome has been proposed as a contributor to Alzheimer’s disease (AD) pathogenesis via the microbiota–gut–brain axis, but findings across cohorts are inconsistent and scarce data exist from Central Asian populations. We used shotgun metagenomic sequencing to compare the gut microbiome of AD patients and cognitively healthy controls from Kazakhstan. In a cross-sectional case–control study (35 AD, 39 Control), we profiled taxonomic and functional (HUMAnN pathway) composition, and compared alpha/beta diversity, individual taxa and pathways, and their association with clinical and demographic variables (Mann–Whitney U test, PERMANOVA/PERMDISP, OLS regression, all BH-FDR corrected, sensitivity analysis using ANCOM-BC2), with sensitivity analyses adjusting for age and BMI and applying Bonferroni correction. Within the AD group, circulating adiponectin—measured only in this group—was examined for associations with microbiome features in an exploratory analysis. Alpha diversity was lower in AD (q < 0.05). Community composition also separated by group on PERMANOVA (R2 = 8.6%, p = 0.001), and this separation held after adjusting for age and BMI. A total of 178 taxa differed significantly between groups (BH-FDR; 37 were also Bonferroni-significant), most prominently depletion of Faecalibacterium and enrichment of Eisenbergiella and Desulfovibrio in AD; 100 pathways differed significantly (20 Bonferroni-significant). Three clinical/demographic variables (total bilirubin, atherogenic index, BMI) were associated with specific taxa or pathways. Within the AD group, adiponectin correlated negatively with the pathway assimilatory sulfate reduction IV (rho = −0.60, q = 0.015). AD in this Central Asian cohort was associated with a less diverse, compositionally distinct gut microbiome, with depletion of butyrate-producing Firmicutes and enrichment of sulfate-reducing taxa, alongside other taxa whose direction of association differed from prior reports.
SN  - 1422-0067
ER  -