Evidence map›Paper›PMID 40886152›Full record

ArticleGut microbes2025

Early-life gut microbiome maturity regulates blood-brain barrier and cognitive development.

Zachary M Zemmel, Xiaobing Fan, Yueyue Yu, Erica Markiewicz, Hsiu-Ming Tsai, Lei Lu, Jessica C Little, Ramanujam Ramaswamy, Bree Andrews, Erika C Claud and 1 more

Abstract read
In one paragraph

Article in Gut microbes, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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.

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

6 citing papers in PubMed.

  1. Review
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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

11 authors.

Zachary M ZemmelPrinceton Neuroscience Institute, Princeton University, Princeton, NJ, USA.ORCID 0000-0002-1032-4450
Xiaobing FanDepartment of Radiology, University of Chicago, Chicago, IL, USA.ORCID 0000-0001-9004-029X
Yueyue YuCenter for the Science of Early Trajectories, University of Chicago, Chicago, IL, USA.
Erica MarkiewiczDepartment of Radiology, University of Chicago, Chicago, IL, USA.
Hsiu-Ming TsaiDepartment of Radiology, University of Chicago, Chicago, IL, USA.
Lei LuCenter for the Science of Early Trajectories, University of Chicago, Chicago, IL, USA.
Jessica C LittleDuchossois Family Institute, University of Chicago, Chicago, IL, USA.ORCID 0000-0002-8032-1378
Ramanujam RamaswamyDuchossois Family Institute, University of Chicago, Chicago, IL, USA.ORCID 0000-0001-7448-6574
Bree AndrewsDepartment of Pediatrics, University of Chicago, Chicago, IL, USA.
Erika C ClaudUniversity of Chicago Neuroscience Institute, Chicago, IL, USA.
Jing LuCenter for the Science of Early Trajectories, University of Chicago, Chicago, IL, USA.ORCID 0000-0002-0153-9361

Funding

ULTRASTRUCTURE AND CYTOMORPHOLOGY COREP30DK042086 · NIDDK · UNIVERSITY OF CHICAGO · PI CHANG, EUGENE B · 1990 to 2025
$29.8M
Pilot Program CoreP30ES027792 · NIEHS · UNIVERSITY OF CHICAGO · PI Gokhan M. Mutlu, Gail S Prins · 2017 to 2026
$13.6M
The Gut Microbiome Brain Axis and Preterm InfantsR01HD105234 · NICHD · UNIVERSITY OF CHICAGO · PI CLAUD, ERIKA C · 2021 to 2025
$3.4M
Probing short and long term consequences of Small and Large Bowel Microbiota Transplants on Host Physiology: Implications for the development of future live biotherapeuticsR01DK138072 · NIDDK · UNIVERSITY OF CHICAGO · PI EUGENE B CHANG, Kristina Brooke Martinez-Guryn · 2024 to 2026
$2.1M
Microbial-mediated blood-brain barrier development at the intersection of the gut-brain axisR21NS121432 · NINDS · UNIVERSITY OF CHICAGO · PI LU, JING · 2021 to 2022
$451k
NICHD NIH HHS R01 HD105234NIDDK NIH HHS P30 DK042086NIDDK NIH HHS R01 DK138072NIEHS NIH HHS P30 ES027792NINDS NIH HHS R21 NS121432
6 · The paper itself

Abstract

The gut microbiome is an emerging factor in the neurobiology of disease. Blood-brain barrier (BBB) integrity is essential for proper brain function. However, the role the initial microbiome plays in BBB and brain development is unclear. In this study, we colonized germ-free pregnant mice with human full-term- or preterm-infant-derived gut microbiota, thereby establishing these communities in the resulting offspring. We discovered that mice harboring a full-term-associated microbiome exhibited stronger memory and learning capabilities and dramatically decreased early-life BBB permeability when compared to those with a prematurity-associated microbiome. Whole-brain single-cell RNA sequencing revealed downregulation of synaptic signaling genes in BBB cell types of mice with the prematurity-associated microbiome, indicating that microbiome maturity influences BBB transcriptional programs that support cognitive development. Comprehensive metagenomics and metabolomics uncovered bacterial populations and genomic pathways corresponding with decreased levels of circulating long-chain acylcarnitines and lysophosphatidylcholines in mice with the full-term-associated microbiome. Our findings highlight the microbiome as a therapeutic target for improving long-term neurodevelopmental outcomes due to its effect on the early-life BBB.

Indexed as

Blood-Brain BarrierCognitionGastrointestinal MicrobiomeAnimalsBacteriaBrainFemaleGerm-Free LifeHumansMaleMiceMice, Inbred C57BLPregnancyblood–brain barriergut–brain axishost–microbe interactionsmagnetic resonance imagingmetabolomicsneurodevelopmental impairmentshotgun metagenomicssingle-cell RNA sequencing

Identifiers

PMID40886152
PMCPMC12416178

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.