Evidence map›Paper›PMID 41896724›Full record

ArticleGut microbes2026

Circulatory dietary and gut-derived metabolites predict early cognitive decline.

Emily Connell, Saber Sami, Mizanur Khondoker, Anne Marie Minihane, Matthew G Pontifex, Michael Müller, Simon McArthur, Gwenaelle Le Gall, David Vauzour

Abstract read
In one paragraph

Article in Gut microbes, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Article
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

9 authors.

Emily ConnellNorwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom.ORCID 0000-0002-1232-3945
Saber SamiNorwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom.ORCID 0000-0001-5345-0388
Mizanur KhondokerNorwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom.ORCID 0000-0002-1801-1635
Anne Marie MinihaneNorwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom.ORCID 0000-0001-9042-4226
Matthew G PontifexNorwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom.ORCID 0000-0003-2174-2313
Michael MüllerNorwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom.ORCID 0000-0002-5930-9905
Simon McArthurInstitute of Dentistry, Faculty of Medicine & Dentistry, Queen Mary University of London, Blizard Institute, London, United Kingdom.ORCID 0000-0001-8521-1808
Gwenaelle Le GallNorwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom.ORCID 0000-0002-1379-2196
David VauzourNorwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom.ORCID 0000-0001-5952-8756

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionA key component of disease prevention is the identification of at-risk individuals. Microbial dysbiosis in the early stages of cognitive decline and Alzheimer's disease (AD) and can modulate the levels of microbe-derived metabolites (MDM), thought to contribute to neuroinflammation, blood‒brain barrier dysfunction, and neuronal degeneration. However, the precise role of MDM in this process, as well as their potential value as risk factors, remains poorly understood.

methodsMass spectrometry platforms determined the serum concentration of 33 metabolites (13 tryptophan-related compounds, 15 bile acid compounds, 3 TMAO-related metabolites and 2 cresol metabolites) from cognitively healthy subjects, subjective cognitive impairment (SCI) participants and mild cognitive impairment (MCI) participants (

resultsMultiple linear regression modelling, adjusted for sex, BMI, age, albumin (for its role in metabolite transport), liver and kidney function, and background diet, identified key neuroprotective metabolites, namely choline, 5-hydroxyindole acetic acid, and indole propionic acid (IPA), as lower in SCI and MCI individuals compared to healthy controls. In contrast, the cytotoxic metabolite, indoxyl sulfate, and kynurenic acid were elevated. A random forest algorithm with multiclass classification further validated these findings, highlighting six metabolites (indoxyl sulfate, choline, 5-hydroxyindole acetic acid, IPA, kynurenic acid, and kynurenine) as classifiers of early cognitive decline, achieving an area under the curve (AUC) of 0.79.

conclusionThese findings suggest that MDM may serve as putative composite biomarkers of early cognitive decline, offering potential clinical relevance for metabolic risk stratification and supporting the future development of minimally invasive screening tools.

Indexed as

Cognitive DysfunctionGastrointestinal MicrobiomeAgedBacteriaBiomarkersDietDysbiosisFemaleHumansMaleMiddle AgedBiomarkers5-hydroxyindole acetic acidcholinegut-brain axisindole-3-propionic acidindoxyl sulfatekynurenic acidMicrobiomemild cognitive impairmentsubjective cognitive impairment

Identifiers

PMID41896724
PMCPMC13034628

What Socratic holds

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LicenceCC BY
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Registered trials

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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.