Evidence map›Paper›PMID 42716835›Full record

ArticleEBioMedicine2026

Brain-gut crosstalk associated with brain ageing in young and mid-life adults: a multicohort cross-sectional study.

Kanhao Zhao, Gabriel A Vignolle, Jennifer S Labus, Emeran A Mayer, Allison Vaughan, Marika Dy, Priten Vora, Ming W Hung, Keith Vossel, Chris Gill and 7 more

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In one paragraph

Article in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

17 authors.

Kanhao ZhaoUniversity of California, Los Angeles (UCLA), Los Angeles, CA, USA; Goodman-Luskin Microbiome Centre at UCLA, Los Angeles, CA, USA; Vatche and Tamar Manoukian Division of Digestive Diseases, at UCLA, Los Angeles, CA, USA; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: kaz220@stanford.edu.
Gabriel A VignolleUniversity of California, Los Angeles (UCLA), Los Angeles, CA, USA; Goodman-Luskin Microbiome Centre at UCLA, Los Angeles, CA, USA; Vatche and Tamar Manoukian Division of Digestive Diseases, at UCLA, Los Angeles, CA, USA; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Jennifer S LabusUniversity of California, Los Angeles (UCLA), Los Angeles, CA, USA; Goodman-Luskin Microbiome Centre at UCLA, Los Angeles, CA, USA; Vatche and Tamar Manoukian Division of Digestive Diseases, at UCLA, Los Angeles, CA, USA; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Emeran A MayerUniversity of California, Los Angeles (UCLA), Los Angeles, CA, USA; Goodman-Luskin Microbiome Centre at UCLA, Los Angeles, CA, USA; Vatche and Tamar Manoukian Division of Digestive Diseases, at UCLA, Los Angeles, CA, USA; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Allison VaughanUniversity of California, Los Angeles (UCLA), Los Angeles, CA, USA; Goodman-Luskin Microbiome Centre at UCLA, Los Angeles, CA, USA; Vatche and Tamar Manoukian Division of Digestive Diseases, at UCLA, Los Angeles, CA, USA; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Marika DyUniversity of California, Los Angeles (UCLA), Los Angeles, CA, USA; Goodman-Luskin Microbiome Centre at UCLA, Los Angeles, CA, USA; Vatche and Tamar Manoukian Division of Digestive Diseases, at UCLA, Los Angeles, CA, USA; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Priten VoraUniversity of California, Los Angeles (UCLA), Los Angeles, CA, USA; Goodman-Luskin Microbiome Centre at UCLA, Los Angeles, CA, USA; Vatche and Tamar Manoukian Division of Digestive Diseases, at UCLA, Los Angeles, CA, USA; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Ming W HungUniversity of California, Los Angeles (UCLA), Los Angeles, CA, USA; Goodman-Luskin Microbiome Centre at UCLA, Los Angeles, CA, USA; Vatche and Tamar Manoukian Division of Digestive Diseases, at UCLA, Los Angeles, CA, USA; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Keith VosselDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Chris GillNutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, UK.
Daniele Del RioDepartment of Food and Drugs, University of Parma, Parma, Italy.
Catherine StantonAPC Microbiome Ireland, University College Cork, Cork, T12 YT20, Ireland; Food Biosciences Department, Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland.
R Paul RossAPC Microbiome Ireland, University College Cork, Cork, T12 YT20, Ireland.
John F CryanAPC Microbiome Ireland, University College Cork, Cork, T12 YT20, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, T12 YT20, Ireland.
Rima Kaddurah-DaoukDepartment of Precision Behavioral Health, The University of Texas Health Science Centre at Houston, Houston, TX, USA.
Yu ZhangDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA; Institute for Human-Centred Artificial Intelligence (HAI), Stanford University, Stanford, CA, USA.
Arpana ChurchUniversity of California, Los Angeles (UCLA), Los Angeles, CA, USA; Goodman-Luskin Microbiome Centre at UCLA, Los Angeles, CA, USA; Vatche and Tamar Manoukian Division of Digestive Diseases, at UCLA, Los Angeles, CA, USA; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Electronic address: ArpanaChurch@mednet.ucla.edu.

Funding

Project 4 - Mechanistic studies on the role of the gut microbiome in models for Alzheimer's diseaseU19AG063744 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Rima F Kaddurah-Daouk · 2019 to 2026
$54.1M
Peripheral and Central Biomarkers of Alzheimer's Disease in Diverse CohortsU19AG074879 · NIA · MAYO CLINIC JACKSONVILLE · PI Minerva Maria Carrasquillo, NILUFER ERTEKIN-TANER · 2023 to 2026
$42.0M
The National Institute on Aging (NIA) Late Onset of Alzheimer's Disease (LOAD) Family-Based Study (FBS)U24AG056270 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Gary Wayne Beecham, TATIANA M. FOROUD · 2017 to 2026
$31.4M
Metabolomic Signatures for Disease Sub-classification and Target Prioritization in AMP-ADU01AG061359 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, KASTENMULLER, GABI · 2018 to 2022
$10.0M
The Role of Chemical Exposures in Alzheimer's Disease (AD) and its TrajectoryU01AG088562 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Oliver Fiehn, LEE E. GOLDSTEIN · 2024 to 2026
$7.2M
Metabolic Signatures Underlying Vascular Risk Factors for Alzheimer-type DementiasRF1AG051550 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, KLING, MITCHEL ALLAN · 2015 to 2016
$6.3M
Metabolic Networks and Pathways Predictive of Sex Differences in AD Risk and Responsiveness to TreatmentRF1AG059093 · NIA · DUKE UNIVERSITY · PI BRINTON, ROBERTA EILEEN, CHANG, RUI · 2018 to 2018
$5.9M
MAEVE: Microbiota mediated flavonoid metabolites for cognitive healthR01AG081768 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARPANA CHURCH, Emeran A Mayer · 2024 to 2026
$4.6M
Metabolic Networks and Pathways in Alzheimer's DiseaseR01AG046171 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F · 2014 to 2017
$4.4M
Social Isolation and Discrimination as Stressors Influencing Brain-Gut Microbiome Alterations among Filipino and Mexican AmericanR01MD015904 · NIMHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHURCH, ARPANA · 2021 to 2025
$4.1M
In Vivo Studies of the Epileptic HippocampusRF1NS033310 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ENGEL, JEROME NONE, STABA, RICHARD · 2023 to 2023
$3.6M
Metabolic Network Analysis of Biochemical Trajectories in Alzheimer's DiseaseRF1AG057452 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, KASTENMULLER, GABI · 2017 to 2017
$3.5M
NIA NIH HHS R01 AG046171NIA NIH HHS R01 AG081322NIA NIH HHS R01 AG081768NIA NIH HHS R01 AG085518NIA NIH HHS R21 AG080425NIA NIH HHS RF1 AG051550NIA NIH HHS RF1 AG057452NIA NIH HHS RF1 AG058942NIA NIH HHS RF1 AG059093NIA NIH HHS U01 AG061359NIA NIH HHS U01 AG088562NIA NIH HHS U19 AG063744NIA NIH HHS U19 AG074879NIA NIH HHS U24 AG056270NIA NIH HHS UH2 AG083254NIA NIH HHS UH3 AG083254NIDDK NIH HHS K23 DK106528NIDDK NIH HHS R03 DK121025NIMHD NIH HHS R01 MD015904NIMH NIH HHS R01 MH108348NINDS NIH HHS RF1 NS033310
6 · The paper itself

Abstract

backgroundBrain age deviation is a promising neuroimaging biomarker of brain health, but its relevance in young and mid-life adults and its biological underpinnings remain insufficiently characterised. We aimed to test whether a functional-connectivity-derived brain ageing index (BAI) captures reproducible variability in early brain ageing and whether it is associated with cognitive-affective function and gut-derived biological signatures.

methodsWe analysed resting-state fMRI from a discovery cohort (n = 674) with validation in a replication cohort (n = 444) and an independent cohort (n = 344). Whole-brain functional connectivity was computed using a 100-region Schaefer parcellation, and Bayesian ridge regression was used to predict chronological age; BAI was defined as the age-bias-corrected residual (predicted brain age minus chronological age). We tested associations between BAI and cognitive and affective measures across cohorts. In the independent cohort, we applied multi-view sparse partial least squares to integrate stool metagenomic and metabolomic profiles with BAI, and performed KEGG pathway enrichment analyses on features with non-zero weights.

findingsPredicted brain age correlated with chronological age across cohorts (r = 0.50-0.59). Higher BAI was consistently associated with connectivity patterns involving posterior cingulate/praecuneus and medial frontal regions, poorer cognitive performance, particularly working memory and executive function, and greater depressive symptoms. Multi-omics integration identified microbial taxa and stool metabolites, including ceramides, 24-hydroxycholesterol, dicarboxylic acids, and inverse associations with estetrol, linked to BAI. Enrichment analyses suggested involvement of neuroimmune, vascular, synaptic, and mitochondrial pathways.

interpretationA connectivity-derived BAI captures reproducible variability in early brain ageing and links large-scale brain network organisation to gut-derived biological signatures. These findings suggest that BAI captures individual variability associated with brain health-related phenotypes and support the potential association of peripheral brain-gut biological pathways in early brain ageing.

fundingNational Institutes of Health, National Institute on Ageing.

Indexed as

Brain ageingBrain healthCognitive functionFunctional brain connectivityMetabolitesMicrobiome

Identifiers

PMID42716835
PMCPMC13628603

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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 OpenQuestion graph.