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Akkermansia muciniphila improving depression-like behaviors by regulating glycerophospholipid metabolism in gut-brain axis.

Overview

Authors: Fei He1, Shunjie Bai2, Jing Xie3, Yongzhi Zhang1, Ke Xu4,5, Jiaolin Wang1, Yi Ren4,5, Zhe Ren4,5, Jianjun Chen1, Ying Wang6, Peng Xie4,5
  1. Institute of Neuroscience, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China
  2. Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  3. Chongqing Key Laboratory of Emergency Medicine, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, China
  4. Department of Neurology, National Health Commission Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  5. Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  6. Department of Rehabilitation, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
Journal: Frontiers in pharmacology, volume 17, article 1790866
Dates: received 19 January 2026; accepted 9 March 2026; published online 1 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.3389/fphar.2026.1790866 · PMID 41993570 · PMCID PMC13080252 · OpenAlex W7147834535
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), depression (population), cellular / molecular (subfield)
Methods: Statistics, Connectivity, Smoothing, state filtering, decompositions
Keywords: Akkermansia muciniphila, depression, glycerophospholipid, inflammation, lipids
Topic: Gut microbiota and health (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: National Natural Science Foundation of China (CSTB2025NSCQ-GPX1158, CSTB2025NSCQ)
Citations: not cited yet (Europe PMC); 66 references in the paper

Abstract

Background: Akkermansia muciniphila (AKK) is a potential probiotic. Our previous studies have shown that it could alleviate depressive-like behaviors (DLBs) in mice by inhibiting neuroinflammation in brain. To further explore its antidepressant effect, this study focused on the effects of AKK on the metabolic activities in gut-brain axis.

Methods: After chronic restraint stress (CRS) depression model was successfully built, AKK was used as intervention method for 3 weeks. The gut microbiome in feces and two intestinal permeability proteins in colon (Claudin-1, Occludin) were measured, and the metabolites in feces, colon, liver, and prefrontal cortex were also measured. In addition, two inflammation-related factors in hippocampus (Free fatty acid receptors 3 (FFAR3), phosphorylated NF-κB p65 (p-p65)) were measured.

Results: AKK was successfully colonized in gut of chronic restraint stress (CRS) mice. The DLBs in CRS mice receiving AKK (CRS + AKK) were significantly improved, along with the improved gut microbiome. Both Claudin-1 and Occludin in colon were significantly increased in CRS + AKK mice compared to CRS mice receiving phosphate buffer saline (PBS) (CRS + p). Metabolomics analysis indicated that AKK could significantly improve the changed lipids and lipid-like molecules in gut-brain axis of CRS mice; and function analysis using differential metabolites showed that AKK could significantly improve the disordered glycerophospholipid metabolism in feces, colon, liver, and prefrontal cortex of CRS mice. Additionally, we found that FFAR3 and phosphorylated NF-κB p65 were increased and decreased, respectively, in hippocampus of CRS + AKK mice compared to CRS + p mice.

Conclusion: Our results suggested that AKK might improve the disturbances of gut microbiome, intestinal permeability, host’s lipid metabolism and inflammation levels in hippocampus. Glycerophospholipid metabolism in gut-brain axis might be the important mediator in the process of AKK producing antidepressants effects.

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

Code

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Data

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Data availability statement

The datasets generated during the current study were available in online repositories. The names of the repository/repositories and accession number(s) can be found below: http://www.ncbi.nlm.nih.gov/bioproject/1400281.

Reproduced under the paper's license (CC BY), 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 2, 28 September 2026

  • Funding: added Natural Science Foundation of Chongqing: CSTB2025NSCQ-GPX1158, CSTB2025NSCQ

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 11 authors, 5 keywords, 66 references.

Cite

This paper

He, F., Bai, S., Xie, J., Zhang, Y., Xu, K., Wang, J., Ren, Y., Ren, Z., Chen, J., Wang, Y., & Xie, P. (2026). Akkermansia muciniphila improving depression-like behaviors by regulating glycerophospholipid metabolism in gut-brain axis. Frontiers in pharmacology, 17, 1790866. https://doi.org/10.3389/fphar.2026.1790866

BibTeX

@article{he2026akkermansia,
author = {He, Fei and Bai, Shunjie and Xie, Jing and Zhang, Yongzhi and Xu, Ke and Wang, Jiaolin and Ren, Yi and Ren, Zhe and Chen, Jianjun and Wang, Ying and Xie, Peng},
title = {{Akkermansia muciniphila improving depression-like behaviors by regulating glycerophospholipid metabolism in gut-brain axis}},
journal = {Frontiers in pharmacology},
year = {2026},
month = apr,
volume = {17},
pages = {1790866},
publisher = {Frontiers Media SA},
issn = {1663-9812},
doi = {10.3389/fphar.2026.1790866},
url = {https://doi.org/10.3389/fphar.2026.1790866},
pmid = {41993570},
pmcid = {PMC13080252}
}

RIS

TY - JOUR
AU - He, Fei
AU - Bai, Shunjie
AU - Xie, Jing
AU - Zhang, Yongzhi
AU - Xu, Ke
AU - Wang, Jiaolin
AU - Ren, Yi
AU - Ren, Zhe
AU - Chen, Jianjun
AU - Wang, Ying
AU - Xie, Peng
TI - Akkermansia muciniphila improving depression-like behaviors by regulating glycerophospholipid metabolism in gut-brain axis
T2 - Frontiers in pharmacology
J2 - Front Pharmacol
PY - 2026
DA - 2026/04/01
VL - 17
SP - 1790866
SN - 1663-9812
PB - Frontiers Media SA
DO - 10.3389/fphar.2026.1790866
UR - https://doi.org/10.3389/fphar.2026.1790866
LA - en
ER -

CSL-JSON

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