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Enteric-colonized <i>Cronobacter</i> spp. can disrupt the central nervous system without translocation across the host barriers.

Overview

Authors: Jillinda Yi Ling Toh1, Sok Ching Tay1, Zihui Lin2, Evelyn Xiu Ling Loo3,4, Jia Xu3,5, Johan Gunnar Eriksson3,6,7,8, Peter D Gluckman3,9, Yap Seng Chong3,6, Michael Meaney10, Fabian Yap11,12, Cleo Tay13,14, Xiao Pan Ding14, Dan Li1
ORCID iDs: Dan Li
14 affiliations
  1. Department of Food Science & Technology, Faculty of Science, National University of Singapore, Singapore, Singapore
  2. Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou, China
  3. Institute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
  4. Department of Paediatrics and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  5. Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  6. Department of Obstetrics and Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  7. Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland
  8. Folkhälsan Research Center, Helsinki, Finland
  9. Liggins Institute, University of Auckland, Auckland, New Zealand
  10. Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, Canada
  11. Department of Paediatric Endocrinology, KK Women's and Children's Hospital, Singapore, Singapore
  12. SingHealth, Duke-NUS Paediatrics Academic Clinical Programme, Singapore, Singapore
  13. Department of Psychology, Stanford University, Stanford, CA, USA
  14. Department of Psychology, National University of Singapore, Singapore, Singapore
Institutions: National University of Singapore (Singapore); Zhejiang University (China); Agency for Science, Technology and Research (Singapore); University of Helsinki (Finland); Folkhälsans Forskningscentrum (Finland); University of Auckland (New Zealand); McGill University (Canada); SingHealth (Singapore); SingHealth Duke-NUS Academic Medical Centre (Singapore); KK Women's and Children's Hospital (Singapore); Duke-NUS Medical School (Singapore); Stanford University (United States)
Journal: Gut microbes, volume 18, issue 1, article 2694805
Dates: received 11 February 2026; accepted 22 June 2026; published online 16 July 2026; in print December 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1080/19490976.2026.2694805 · PMID 42464430 · PMCID PMC13387119 · OpenAlex W7169577406
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), human (organism), zebrafish (organism), cognitive (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, Evoked potentials
Keywords: Cronobacter, gut–brain axis, social-cognitive-emotional performance, lipopolysaccharides, zebrafish
MeSH: Central Nervous System*, Cronobacter sakazakii*, Enterobacteriaceae Infections*, Gastrointestinal Microbiome*, Animals, Bacterial Translocation, Feces, Humans, Lipopolysaccharides, Virulence, Zebrafish (* major topic)
Topic: Enterobacteriaceae and Cronobacter Research (Endocrinology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: National University of Singapore (E-160-00-0015-01); National Research Foundation Singapore (OF-LCG, MOH-000504)
Citations: not cited yet (Europe PMC); 104 references in the paper

Abstract

Cronobacter sakazakii is an opportunistic foodborne pathogen known to cause severe neonatal infections. However, its subclinical effects on human health remain largely unexplored. Here, we report that intestinal colonization by Cronobacter is potentially correlated with human neurobehavioral alterations in the absence of bacterial translocation across host barriers. Analysis of fecal microbiota from the children in GUSTO cohort revealed that Cronobacter abundance was significantly and positively correlated with their emotional reactivity and affective problem scores, suggesting an association between gut Cronobacter colonization and emotional dysfunction. Using a zebrafish larvae model, we demonstrated that enteric colonization by C. sakazakii ATCC 25944 triggered a distinctive bending phenotype and locomotor instability, indicative of central nervous system (CNS) disturbance. Multi-omics profiling revealed upregulation of genes related to circadian rhythm (e.g., per2, nr1d1, nr1d2) and neuropsychiatric markers (hint1), alongside metabolic dysregulation involving lipid classes linked to neurodegenerative stress. Random mutagenesis coupled with whole-genome sequencing identified modifier variants in genes associated with lipopolysaccharide (LPS) biosynthesis and fimbrial adhesion, which attenuated the neurotoxic phenotype. LPS isolated from wild-type C. sakazakii, but not from mutants, reproduced the CNS impairment phenotype, highlighting its crucial virulence role. Collectively, our findings provide the first evidence that enteric Cronobacter colonization may affect human emotional development via gut-derived LPS signaling, emphasizing its underestimated role in the gut–brain axis and neurobehavioral health.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

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Data

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Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and at Mendeley Data via the DOI: 10.17632/5bbr262sw7.1.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 13 authors, 5 keywords, 11 MeSH terms, 2 funders, 101 references.

Cite

This paper

Toh, J. Y. L., Tay, S. C., Lin, Z., Loo, E. X. L., Xu, J., Eriksson, J. G., Gluckman, P. D., Chong, Y. S., Meaney, M., Yap, F., Tay, C., Ding, X. P., & Li, D. (2026). Enteric-colonized <i>Cronobacter</i> spp. can disrupt the central nervous system without translocation across the host barriers. Gut microbes, 18(1), 2694805. https://doi.org/10.1080/19490976.2026.2694805

BibTeX

@article{toh2026enteric,
author = {Toh, Jillinda Yi Ling and Tay, Sok Ching and Lin, Zihui and Loo, Evelyn Xiu Ling and Xu, Jia and Eriksson, Johan Gunnar and Gluckman, Peter D and Chong, Yap Seng and Meaney, Michael and Yap, Fabian and Tay, Cleo and Ding, Xiao Pan and Li, Dan},
title = {{Enteric-colonized \<i\>Cronobacter\</i\> spp. can disrupt the central nervous system without translocation across the host barriers}},
journal = {Gut microbes},
year = {2026},
month = jul,
volume = {18},
number = {1},
pages = {2694805},
publisher = {Taylor \& Francis},
issn = {1949-0976},
doi = {10.1080/19490976.2026.2694805},
url = {https://doi.org/10.1080/19490976.2026.2694805},
pmid = {42464430},
pmcid = {PMC13387119}
}

RIS

TY - JOUR
AU - Toh, Jillinda Yi Ling
AU - Tay, Sok Ching
AU - Lin, Zihui
AU - Loo, Evelyn Xiu Ling
AU - Xu, Jia
AU - Eriksson, Johan Gunnar
AU - Gluckman, Peter D
AU - Chong, Yap Seng
AU - Meaney, Michael
AU - Yap, Fabian
AU - Tay, Cleo
AU - Ding, Xiao Pan
AU - Li, Dan
TI - Enteric-colonized <i>Cronobacter</i> spp. can disrupt the central nervous system without translocation across the host barriers
T2 - Gut microbes
J2 - Gut Microbes
PY - 2026
DA - 2026/07/16
VL - 18
IS - 1
SP - 2694805
SN - 1949-0976
PB - Taylor & Francis
DO - 10.1080/19490976.2026.2694805
UR - https://doi.org/10.1080/19490976.2026.2694805
LA - en
ER -

CSL-JSON

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