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Microbiota fasting-related changes ameliorate cognitive decline in obesity and boost ex vivo microglial function through the gut-brain axis
Virginia Mela, Violeta Heras, Monika Iešmantaitė, Maria Luisa García‐Martín, Manuel Bernal, Joel D. Posligua-García, Alba Subiri-Verdugo, José Ignacio Martínez‐Montoro et al.. Gut, 2025-05-07
Topic: Brain proteins, microglia and lab models
Both the Keto and ADF groups demonstrated significant weight loss, but cognitive performance improved most notably in the ADF group, in association with reduced inflammation. Diet-related microbiota composition was correlated with the cognitive outcomes in the human study. Mice models confirmed that the cognitive benefits of ADF were microbiota-dependent and linked to enhanced microglial phagocytic capacity and reduced inflammation, accompanied by changes in microglia morphology. Fasting-induced modifications in gut microbiota contribute to cognitive improvement in individuals with obesity, with microglial cells playing a crucial mediatory role. Among the interventions, ADF most effectively enhanced microglial function and cognitive performance, suggesting its potential as a therapeutic strategy for obesity-related cognitive decline. Further studies are required to fully elucidate the underlying mechanisms. TRIAL REGISTRATION NUMBER: NCT04453150.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Mela, V., Heras, V., Iešmantaitė, M., García‐Martín, M. L., Bernal, M., Posligua-García, J. D., et al. (2025). Microbiota fasting-related changes ameliorate cognitive decline in obesity and boost ex vivo microglial function through the gut-brain axis. Gut. https://doi.org/10.1136/gutjnl-2025-335353
Vancouver
Mela V, Heras V, Iešmantaitė M, García‐Martín ML, Bernal M, Posligua-García JD, et al. Microbiota fasting-related changes ameliorate cognitive decline in obesity and boost ex vivo microglial function through the gut-brain axis. Gut. 2025. doi:10.1136/gutjnl-2025-335353. PMID: 40335161.
BibTeX
@article{mela2025-40335161,
author = {Mela, Virginia and Heras, Violeta and Iešmantaitė, Monika and García‐Martín, Maria Luisa and Bernal, Manuel and Posligua-García, Joel D. and Subiri-Verdugo, Alba and Martínez‐Montoro, José Ignacio and others},
title = {{Microbiota fasting-related changes ameliorate cognitive decline in obesity and boost ex vivo microglial function through the gut-brain axis}},
journal = {Gut},
year = {2025},
doi = {10.1136/gutjnl-2025-335353},
pmid = {40335161},
url = {https://doi.org/10.1136/gutjnl-2025-335353}
}
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Key findings
- Both the Keto and ADF groups demonstrated significant weight loss, but cognitive performance improved most notably in the ADF group, in association with reduced inflammation.
- Diet-related microbiota composition was correlated with the cognitive outcomes in the human study.
- Mice models confirmed that the cognitive benefits of ADF were microbiota-dependent and linked to enhanced microglial phagocytic capacity and reduced inflammation, accompanied by changes in microglia morphology.
- Fasting-induced modifications in gut microbiota contribute to cognitive improvement in individuals with obesity, with microglial cells playing a crucial mediatory role.
- Among the interventions, ADF most effectively enhanced microglial function and cognitive performance, suggesting its potential as a therapeutic strategy for obesity-related cognitive decline.
Why it matters
In this study, alternate-day fasting improved cognitive performance most notably and was linked to reduced inflammation, and mouse experiments showed the cognitive benefits depended on gut microbiota and enhanced microglial function. The authors state that further studies are required to fully explain the mechanisms, so this is not yet a proven treatment for Alzheimer's.
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Study details
- Participants96
- Evidence strengthHigh
How this study scored 53/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Gut) |
| Journal's citation record | 3 / 4 | Gut: journal h-index 451 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 96 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 17 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 4.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 17 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Francisco José Tinahones: h-index 86 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Instituto de Salud Carlos III: institution h-index 649 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40335161) |
| Free to read | 2 / 2 | Free to read |
| Total | 53 / 100 | — |
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