Evidence mapPaperPMID 40335161Full record

Trial reportGut2025

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 Iesmantaite, María Luisa García-Martín, Manuel Bernal, Joel D Posligua-García, Alba Subiri-Verdugo, José Ignacio Martínez-Montoro, Ana María Gómez-Pérez, Borja Bandera and 2 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Gut, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04453150 (Ketone Bodies and Gut Microbiota Role in the Dietetic Approach of Obesity), which is not on this map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04453150 nacompletednot on this map

Ketone Bodies and Gut Microbiota Role in the Dietetic Approach of Obesity

TypeinterventionalSponsorFundación Pública Andaluza para la Investigación de Málaga en Biomedicina y SaludRan2020 to 2022Enrolled150ConditionsObesityArmsStandard hypocaloric die, Intermittent fasting 16/8 (early fasting), Intermittent fasting 16/8 (late fasting), Alternate-day fasting, Ketogenic diet
3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Review
  2. The Gut Microbiome-Endocrine Axis in Obesity: Mechanisms and Therapeutics.Journal of gastroenterology and hepatology · 2026
    Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Changes in the brain [NADFrontiers in aging neuroscience · 2026
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Virginia MelaDepartment of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, Málaga, Spain virginiamelarivas@gmail.com.ORCID 0000-0001-7702-0972
Violeta Heras *Department of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, Málaga, Spain.
Monika Iesmantaite *Department of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, Málaga, Spain.
María Luisa García-MartínBiomedical Magnetic Resonance Laboratory-BMRL, Fundación Pública Andaluza Progreso y Salud (FPS), Seville, Spain.
Manuel BernalDepartament of Molecular Biology and Biochemistry, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain.ORCID 0000-0003-0412-3035
Joel D Posligua-GarcíaDepartament of Molecular Biology and Biochemistry, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain.
Alba Subiri-VerdugoDepartment of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, Málaga, Spain.
José Ignacio Martínez-MontoroDepartment of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, Málaga, Spain.
Ana María Gómez-PérezDepartment of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, Málaga, Spain.
Borja BanderaDepartment of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, Málaga, Spain.
Isabel Moreno-IndiasDepartment of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, Málaga, Spain.
Francisco J TinahonesDepartment of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, Málaga, Spain.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundObesity-related cognitive decline is linked to gut microbiota dysbiosis, with emerging evidence suggesting that dietary interventions may ameliorate cognitive impairment via gut-brain axis modulation. The role of microglial cells in this process remains underexplored.

objectiveTo investigate how diet-induced changes in gut microbiota influence cognitive function in individuals with obesity and their microglial activity, and to determine the impact of specific dietary interventions.

designThis study included 96 participants with obesity who were randomised into three dietary intervention groups: Mediterranean diet (Med), alternate-day fasting (ADF) and ketogenic diet (Keto). Cognitive performance and microbiota composition were assessed pre-intervention and post-intervention. The effects of microbiota-related changes on microglial function were further evaluated in mice models through faecal transplantation and in vitro model with microbiota exosome treatment.

resultsBoth 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.

conclusionFasting-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.

Indexed as

Brain-Gut AxisCognitive DysfunctionGastrointestinal MicrobiomeMicrogliaObesityAdultAnimalsDiet, KetogenicDiet, MediterraneanDysbiosisFastingFecal Microbiota TransplantationFemaleHumansMaleMicedietmetabolomicsmicrobiomeneurobiologyobesity

Identifiers

PMID40335161
PMCPMC12917722

What Socratic holds

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LicenceCC BY-NC
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.