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The gut-brain axis in Alzheimer's disease: early detection, microbial metabolites, mechanisms, and therapeutic opportunities
Chenyu Liu, Zihan Zhu, Huang Lin, William S Bush, Robert R Jenq, Fabio Cominelli, Jagan A Pillai, Jonathan L Haines et al.. Frontiers in molecular biosciences, 2026-06-04
Topic: Gut, metabolism and diet
Alzheimer's disease (AD), the leading cause of dementia worldwide, imposes a growing clinical and societal burden, yet no therapies have been proven to alter its progression despite decades of intensive research. As traditional targets have yielded limited success, attention has shifted to modifiable upstream pathways, notably the gut-brain axis, a bidirectional system linking gut microbiota with CNS function. Emerging evidence indicates that microbial dysbiosis may influence key processes leading to AD, including neuroinflammation, amyloid and tau pathology, and cognitive decline. While microbiome composition is associated with AD, it remains unclear at which stage-preclinical, mild cognitive impairment (MCI), or AD dementia-these differences first arise, or how specific risk bacteria and metabolites contribute to progression. The precise roles of these microbes and metabolites in AD pathology or brain resilience also remain poorly understood, and few microbiome-targeted treatments have been validated in humans. Existing reviews often overlook host-specific factors that influence microbiome composition and confound associations with AD. To bridge these gaps, we summarize human studies published in the past 5 years. The literature suggests that gut microbial changes may precede clinical symptoms, with consistent dysbiosis observed in AD patients. We adopt a microbiome-centered perspective emphasizing bacteria-driven and metabolite-driven mechanisms, each playing distinct yet complementary roles in neural and bloodstream pathways. These pathways offer potential targets for microbiome-based prevention and treatment but require more human validation. Future studies should leverage longitudinal, multi-omics approaches and artificial intelligence (AI) tools while rigorously accounting for confounders to improve early detection and develop personalized therapies for AD.
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APA 7th
Liu, C., Zhu, Z., Lin, H., Bush, W. S., Jenq, R. R., Cominelli, F., et al. (2026). The gut-brain axis in Alzheimer's disease: early detection, microbial metabolites, mechanisms, and therapeutic opportunities. Frontiers in molecular biosciences. https://doi.org/10.3389/fmolb.2026.1735332
Vancouver
Liu C, Zhu Z, Lin H, Bush WS, Jenq RR, Cominelli F, et al. The gut-brain axis in Alzheimer's disease: early detection, microbial metabolites, mechanisms, and therapeutic opportunities. Frontiers in molecular biosciences. 2026. doi:10.3389/fmolb.2026.1735332. PMID: 42325435.
BibTeX
@article{liu2026-42325435,
author = {Liu, Chenyu and Zhu, Zihan and Lin, Huang and Bush, William S and Jenq, Robert R and Cominelli, Fabio and Pillai, Jagan A and Haines, Jonathan L and others},
title = {{The gut-brain axis in Alzheimer's disease: early detection, microbial metabolites, mechanisms, and therapeutic opportunities}},
journal = {Frontiers in molecular biosciences},
year = {2026},
doi = {10.3389/fmolb.2026.1735332},
pmid = {42325435},
url = {https://doi.org/10.3389/fmolb.2026.1735332}
}
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Key findings
- Emerging evidence indicates that microbial dysbiosis may influence key processes leading to AD, including neuroinflammation, amyloid and tau pathology, and cognitive decline.
- While microbiome composition is associated with AD, it remains unclear at which stage-preclinical, mild cognitive impairment (MCI), or AD dementia-these differences first arise, or how specific risk bacteria and metabolites contribute to progression.
- The literature suggests that gut microbial changes may precede clinical symptoms, with consistent dysbiosis observed in AD patients.
Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 61/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 34 of the 56 points we could judge it on, which is 61 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in molecular biosciences) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42325435) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 34 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 34 of the 56 points we could judge it on is 61 out of 100. |
| Total | 61 / 100 | — |
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