Evidence map›Paper›PMID 33535879›Full record

ArticleGut microbes

Involvement of the microbiota-gut-brain axis in chronic restraint stress: disturbances of the kynurenine metabolic pathway in both the gut and brain.

Yuanyuan Deng, Manfei Zhou, Junfeng Wang, Jiaxi Yao, Jing Yu, Wenwei Liu, Linlin Wu, Jun Wang, Rong Gao

Open access · goldAbstract read
In one paragraph

Article in Gut microbes. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
178citing papers in PubMed, 5 pooled it
12.9field-weighted citation impact, top 1% of its field
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

178 citing papers in PubMed, 5 syntheses or guidelines pooled it, 310 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
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  12. Gut microbiota in health and disease.Molecular biomedicine · 2026
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  19. Efavirenz-Altered Gut-Microbiota,International journal of molecular sciences · 2026
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  20. Community-acquired pneumonia withJournal of thoracic disease · 2026
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118 more citing papers are in PubMed but not listed here.

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 at 2 institutions in 3 countries.

Yuanyuan DengDepartment of Hygienic Analysis and Detection, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University , Nanjing China.
Manfei ZhouDepartment of Hygienic Analysis and Detection, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University , Nanjing China.
Junfeng WangDepartment of Hygienic Analysis and Detection, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University , Nanjing China.
Jiaxi YaoDepartment of Hygienic Analysis and Detection, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University , Nanjing China.
Jing YuDepartment of Hygienic Analysis and Detection, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University , Nanjing China.
Wenwei LiuDepartment of Physical and Chemical Inspection, Wuxi Center for Disease Control and Prevention , Wuxi, China.
Linlin WuDepartment of Physical and Chemical Inspection, Wuxi Center for Disease Control and Prevention , Wuxi, China.
Jun WangDepartment of Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University , Nanjing, China.
Rong GaoDepartment of Hygienic Analysis and Detection, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University , Nanjing China.
Ministry of Education · KRWuxi Municipal Product Quality Supervision and Inspection Institute · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Emerging evidence suggests that the gut microbiota may interact with the host brain and play pivotal roles in the pathogenesis of neuropsychiatric disorders. However, the mechanism underlying reciprocal interactions along the microbiota-gut-brain axis in depression remains unclear. In this study, a murine model of chronic restraint stress (CRS) was established to investigate the metabolic signaling of tryptophan (Trp) neurotransmission at the intestinal and central levels in depression. The results showed that CRS mice displayed depression- and anxiety-like behaviors. Additionally, kynurenine (Kyn) and its metabolites, an important Trp metabolic pathway, were strongly activated in the brain. Intriguingly, the Kyn toxic signaling was exacerbated in the gut, especially in the colon. Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme responsible for Kyn metabolic pathway initiation, was significantly upregulated in the brain and gut in CRS mice compared with control mice, promoting transfer of Trp metabolic pathway to Kyn signaling. Additionally, administration of IDO inhibitor, 1-methyl-tryptophan (1-MT), partially rescued CRS-induced depression- and anxiety-like changes. Moreover, the enhanced intestinal permeability mediated by CRS allowed toxic metabolites to "leak" into the bloodstream. The microbiome profiles of CRS mice displayed obviously altered taxonomic composition and negative correlations were observed between

Indexed as

AnimalsBacteroidetesBrainBrain-Gut AxisDepressionDysbiosisGastrointestinal MicrobiomeIndoleamine-Pyrrole 2,3,-DioxygenaseIntestinesKynurenineMaleMiceNeurotransmitter AgentsProbioticsRestraint, PhysicalTryptophanIndoleamine-Pyrrole 2,3,-DioxygenaseKynurenineNeurotransmitter AgentsTryptophanDepressionkynureninemicrobiotaserotonintryptophan metabolism

Identifiers

PMID33535879
PMCPMC7872056
OpenAlexW3127728724

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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 OpenQuestion graph.