Gut microbiota-tryptophan-serotonin axis drives anxiety-like behavior via NLRP3-mediated neuronal pyroptosis in the medial prefrontal cortex

PAPER manual Apoptosis 2026 Animal study Effect: harm Evidence: Low

Read original paper → DOI: 10.1007/s10495-026-02356-5 PMID: 42106547 Evidence Lab

Abstract

The gut-brain axis plays a critical role in anxiety disorders, yet the underlying mechanisms remain incompletely understood. Using a mouse model of radiofrequency radiation (RFR)-induced anxiety-like behaviors, we employed gut microbiota intervention, regulation of tryptophan metabolites, and other methods to investigate the impact of the gut-brain axis on brain function changes. It was found that gut microbiota dysbiosis disrupts tryptophan metabolism, leading to reduced serotonin (5-HT) levels and NLRP3 inflammasome-mediated neuronal pyroptosis in the medial prefrontal cortex (mPFC). Probiotic intervention restored microbial homeostasis, normalized central 5-HT metabolism, suppressed neuronal pyroptosis, and partially alleviated anxiety-like behaviors. Similarly, treatment with the selective serotonin reuptake inhibitor (SSRI) paroxetine increased brain 5-HT, attenuated NLRP3 activation and pyroptosis, and improved behavioral outcomes. These findings reveal that perturbations in gut-brain tryptophan metabolism are strongly correlated with anxiety-like behaviors via neuroinflammatory pyroptotic pathways, offering new mechanistic insights and potential therapeutic targets for anxiety disorders.

AI evidence extraction

At a glance

Study type

Animal study

Effect direction

harm

Population

Mouse model of radiofrequency radiation-induced anxiety-like behaviors

Sample size

—

Exposure

RF other

Evidence strength

Low

Confidence: 91% · Peer-reviewed: yes

Main findings

In a mouse model of radiofrequency radiation-induced anxiety-like behaviors, gut microbiota dysbiosis was associated with disrupted tryptophan metabolism, reduced serotonin levels, and NLRP3-mediated neuronal pyroptosis in the medial prefrontal cortex. Probiotic intervention and paroxetine treatment restored aspects of 5-HT metabolism, reduced pyroptosis-related signaling, and partially improved anxiety-like behavioral outcomes.

Outcomes measured

anxiety-like behaviors
gut microbiota dysbiosis
tryptophan metabolism
serotonin (5-HT) levels
NLRP3 inflammasome activation
neuronal pyroptosis in the medial prefrontal cortex

Limitations

Animal study
Exposure details such as frequency, SAR, and duration were not provided in the abstract
Sample size was not reported in the abstract
Findings are described as correlated/mechanistic within a mouse model

View raw extracted JSON

{
    "study_type": "animal",
    "exposure": {
        "band": "RF",
        "source": "other",
        "frequency_mhz": null,
        "sar_wkg": null,
        "duration": null
    },
    "population": "Mouse model of radiofrequency radiation-induced anxiety-like behaviors",
    "sample_size": null,
    "outcomes": [
        "anxiety-like behaviors",
        "gut microbiota dysbiosis",
        "tryptophan metabolism",
        "serotonin (5-HT) levels",
        "NLRP3 inflammasome activation",
        "neuronal pyroptosis in the medial prefrontal cortex"
    ],
    "main_findings": "In a mouse model of radiofrequency radiation-induced anxiety-like behaviors, gut microbiota dysbiosis was associated with disrupted tryptophan metabolism, reduced serotonin levels, and NLRP3-mediated neuronal pyroptosis in the medial prefrontal cortex. Probiotic intervention and paroxetine treatment restored aspects of 5-HT metabolism, reduced pyroptosis-related signaling, and partially improved anxiety-like behavioral outcomes.",
    "effect_direction": "harm",
    "limitations": [
        "Animal study",
        "Exposure details such as frequency, SAR, and duration were not provided in the abstract",
        "Sample size was not reported in the abstract",
        "Findings are described as correlated/mechanistic within a mouse model"
    ],
    "evidence_strength": "low",
    "confidence": 0.91000000000000003108624468950438313186168670654296875,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "radiofrequency radiation",
        "RFR",
        "mouse model",
        "anxiety-like behavior",
        "gut-brain axis",
        "gut microbiota",
        "tryptophan metabolism",
        "serotonin",
        "5-HT",
        "NLRP3 inflammasome",
        "neuronal pyroptosis",
        "medial prefrontal cortex"
    ],
    "suggested_hubs": []
}

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AI-extracted fields are generated from the abstract/metadata and may be incomplete or incorrect. This content is for informational purposes only and is not medical advice.

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