Evidence map›Paper›PMID 33096252›Full record

ArticleBrain, behavior, and immunity2021

Microbiota metabolites modulate the T helper 17 to regulatory T cell (Th17/Treg) imbalance promoting resilience to stress-induced anxiety- and depressive-like behaviors.

Susan Westfall, Francesca Caracci, Danyue Zhao, Qing-Li Wu, Tal Frolinger, James Simon, Giulio Maria Pasinetti

Open access · hybridAbstract read
In one paragraph

Article in Brain, behavior, and immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 6 pooled it
4.1field-weighted citation impact, top 4% 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

88 citing papers in PubMed, 6 syntheses or guidelines pooled it, 152 citations in OpenAlex.

  1. Pooled it
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  11. The gut-bone-inflammation axis: intestinal barrier disruption as a central driver of osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
    Review
  12. Article
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  16. Article
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  19. The emerging role of T cells in depression.Frontiers in psychiatry · 2026
    Review
  20. Gut Microbiota-Driven Pathways Linking Chronic Stress to Tumor Progression.International journal of biological sciences · 2026
    Review

28 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

7 authors at 3 institutions in 1 country.

Susan WestfallIcahn School of Medicine at Mount Sinai, Department of Neurology, New York, NY, USA.
Francesca CaracciIcahn School of Medicine at Mount Sinai, Department of Neurology, New York, NY, USA.
Danyue ZhaoDepartment of Plant Biology, Rutgers University, New Brunswick, NJ, USA.
Qing-Li WuDepartment of Plant Biology, Rutgers University, New Brunswick, NJ, USA.
Tal FrolingerIcahn School of Medicine at Mount Sinai, Department of Neurology, New York, NY, USA.
James SimonDepartment of Plant Biology, Rutgers University, New Brunswick, NJ, USA.
Giulio Maria PasinettiIcahn School of Medicine at Mount Sinai, Department of Neurology, New York, NY, USA; Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA. Electronic address: giulio.pasinetti@mssm.edu.
Icahn School of Medicine at Mount Sinai · USRutgers, The State University of New Jersey · USJames J. Peters VA Medical Center · US

Funding

Pasinetti: Project 3; Role of Microbiome in Promotion of Cognitive and Psychological Resilience (Faith)P50AT008661 · NCCIH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FAITH, JEREMIAH JAMES · 2015 to 2019
$11.2M
Suppression of Immune Signatures of Stress by Polyphenols SupplementsU19AT010835 · NCCIH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SIMON, JAMES E · 2020 to 2024
$6.8M
Novel Prophylactic and Therapeutic Interventions for Stress-Induced DepressionI01BX003005 · VA · JAMES J PETERS VA MEDICAL CENTER · PI PASINETTI, GIULIO MARIA · 2017 to 2022
–
BLR&D Research Career Scientist Award ApplicationIK6BX003785 · VA · JAMES J PETERS VA MEDICAL CENTER · PI PASINETTI, GIULIO MARIA · 2017 to 2025
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BLRD VA I01 BX003005BLRD VA IK6 BX003785NCCIH NIH HHS P50 AT008661NCCIH NIH HHS U19 AT010835
6 · The paper itself

Abstract

Chronic stress disrupts immune homeostasis while gut microbiota-derived metabolites attenuate inflammation, thus promoting resilience to stress-induced immune and behavioral abnormalities. There are both peripheral and brain region-specific maladaptations of the immune response to chronic stress that produce interrelated mechanistic considerations required for the design of novel therapeutic strategies for prevention of stress-induced psychological impairment. This study shows that a combination of probiotics and polyphenol-rich prebiotics, a synbiotic, attenuates the chronic-stress induced inflammatory responses in the ileum and the prefrontal cortex promoting resilience to the consequent depressive- and anxiety-like behaviors in male mice. Pharmacokinetic studies revealed that this effect may be attributed to specific synbiotic-produced metabolites including 4-hydroxyphenylpropionic, 4-hydroxyphenylacetic acid and caffeic acid. Using a model of chronic unpredictable stress, behavioral abnormalities were associated to strong immune cell activation and recruitment in the ileum while inflammasome pathways were implicated in the prefrontal cortex and hippocampus. Chronic stress also upregulated the ratio of activated proinflammatory T helper 17 (Th17) to regulatory T cells (Treg) in the liver and ileum and it was predicted with ingenuity pathway analysis that the aryl hydrocarbon receptor (AHR) could be driving the synbiotic's effect on the ileum's inflammatory response to stress. Synbiotic treatment indiscriminately attenuated the stress-induced immune and behavioral aberrations in both the ileum and the brain while in a gut-immune co-culture model, the synbiotic-specific metabolites promoted anti-inflammatory activity through the AHR. Overall, this study characterizes a novel synbiotic treatment for chronic-stress induced behavioral impairments while defining a putative mechanism of gut-microbiota host interaction for modulating the peripheral and brain immune systems.

Indexed as

Gastrointestinal MicrobiomeMicrobiotaAnimalsAnxietyMaleMicePrebioticsT-Lymphocytes, RegulatoryPrebioticsAdaptive immunityAryl hydrocarbon receptorGut-brain-axisGut microbiotaMetabolomeNeuroinflammationPolyphenolsPsychiatric disordersRegulatory T cellsTh17 cells

Identifiers

PMID33096252
PMCPMC7986984
OpenAlexW3094129766

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.