Gut Microbiome

Alterations of gut microbiota in Down syndrome and their association with Alzheimer's disease.

Pellegrini C, Ravaioli F, et al. • Alzheimer's & dementia : the journal of the Alzheimer's Association • 2026

TL;DR

Adults with Down syndrome display AD-associated changes in gut microbiota partially resembling those reported previously in euploid AD patients, with specific genera showing changes associated with neurocognitive disorder and plasma AD biomarkers.

Key Findings

Results

Adults with Down syndrome showed no significant changes in overall microbial diversity compared to euploid controls.

Study included 58 adults with DS (aged 21-75 years) and 30 euploid controls (aged 25-83 years)
GM was profiled using 16S rRNA sequencing with filtering of low prevalent taxa
Alpha and beta diversity measures did not differ significantly between DS and control groups
Despite lack of overall diversity differences, specific genera were altered

Results

Specific microbial genera including UBA1819 and Intestinibacter were altered in Down syndrome compared to euploid controls.

These genera-level differences were identified despite no overall diversity changes
GM profiling was conducted using 16S rRNA sequencing
Low prevalent taxa were filtered prior to analysis
These alterations represent DS-specific microbiota signatures independent of cognitive status

Results

Down syndrome individuals with major neurocognitive disorder (NcD) showed specific gut microbiota alterations compared to those without NcD.

Major NcD was diagnosed using DSM-5 criteria
Alistipes was increased in DS individuals with NcD
Roseburia was decreased in DS individuals with NcD
These changes partially resemble gut microbiota alterations previously reported in euploid AD patients

Results

Roseburia abundance was negatively associated with plasma Alzheimer's disease biomarkers in adults with Down syndrome.

Plasma biomarkers measured included phosphorylated tau 181 (p-tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP)
Biomarkers were measured using Simoa (single molecule array) technology
Roseburia, which was decreased in DS with NcD, showed a negative association with these AD-related plasma biomarkers
This suggests that lower Roseburia abundance corresponds to higher levels of AD pathology markers

Results

The gut microbiota alterations observed in Down syndrome with neurocognitive disorder partially resemble those reported in euploid Alzheimer's disease patients.

Participants spanned a wide age range: DS adults aged 21-75 years, controls aged 25-83 years
Both fecal and plasma samples were collected and analyzed
The partial overlap with euploid AD microbiota changes suggests shared gut-brain axis mechanisms may contribute to AD risk in DS
DS individuals have a higher risk of AD, providing biological context for these microbiota findings

What This Means

This research suggests that adults with Down syndrome (DS) have specific changes in their gut bacteria that are linked to Alzheimer's disease (AD) development. The study compared gut bacteria profiles from 58 adults with DS and 30 people without DS, finding that while the overall diversity of gut bacteria was similar between groups, certain specific bacterial groups were different. Notably, two bacteria called Alistipes (more abundant) and Roseburia (less abundant) were altered in DS individuals who had already developed significant memory and thinking problems (major neurocognitive disorder). The study also measured blood proteins that serve as markers of Alzheimer's disease — phosphorylated tau 181, neurofilament light chain, and GFAP — and found that lower levels of Roseburia in the gut were associated with higher levels of these AD-related proteins in the blood. This connection between gut bacteria and blood-based AD markers suggests that changes in gut bacteria may be linked to the biological processes driving Alzheimer's disease in people with Down syndrome. This research matters because people with Down syndrome are at very high risk of developing Alzheimer's disease, and understanding the role of gut bacteria in this process could open new avenues for monitoring or potentially intervening in AD progression. The gut bacteria changes seen in DS with cognitive decline partially mirror what has been found in people without DS who have Alzheimer's disease, suggesting shared biological pathways that future treatments might target.

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Citation

Pellegrini C, Ravaioli F, De Fanti S, Siliquini A, Sala C, Rochat M, et al.. (2026). Alterations of gut microbiota in Down syndrome and their association with Alzheimer's disease.. Alzheimer's &amp; dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.71815

Key Findings

What This Means

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