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Open accessFull analysisJul 2, 2026

Honeysuckle-derived nanovesicles (HNVs) attenuate IBD-associated neuropsychiatric disorders via the gut-brain axis: preclinical mouse study

Oral HNV administration reduced anxiety- and depression-like behaviors in DSS-induced chronic colitis mice, with favorable effects on gut-brain axis parameters — no human data exist.

Evidence levelDNarrative / animal / in vitro / mechanistic
Study typein_vitro
Sample
Effect directionMechanistic only
CertaintyVery low
Clinical applicabilityVery low
Overinterpretation risk1/5 · Low
PICO
PopulationMice with DSS-induced chronic colitis (murine model, not humans)
InterventionOral administration of honeysuckle-derived nanovesicles (HNVs)
ComparatorDSS colitis control group without treatment (and healthy group without DSS)
OutcomeAnxiety-like behavior (behavioral assays); Depression-like behavior (forced swim test); Intestinal barrier integrity (tight junction proteins); Pro-inflammatory cytokines (TNF-α, IL-6, IL-1β); Gut microbiota composition; 5-HT/tryptophan metabolism; BDNF/TrkB/GSK3β pathway (hippocampal signaling)

Summary of findings

OutcomeEffect95% CICertaintyClinical relevanceNotes
Anxiety-like behavior (behavioral assays)not reported (qualitative reduction, in the IC 95%, in the SMD/MD provided)Very low1 studies
Depression-like behavior (forced swim test)not reported (qualitative reduction, in the IC 95%, in the SMD/MD provided)Very low1 studies
Intestinal barrier integrity (tight junction proteins)not reported (qualitative preservation occludin/claudin, in the IC 95%)Very low1 studies
Pro-inflammatory cytokines (TNF-α, IL-6, IL-1β)not reported (qualitative reduction, in the IC 95%)Very low1 studies
Gut microbiota compositionnot reported (qualitative reshaping, in the IC 95%)Very low1 studies
5-HT/tryptophan metabolismnot reported (qualitative restoration, in the IC 95%)Very low1 studies
BDNF/TrkB/GSK3β pathway (hippocampal signaling)not reported (qualitative activation, in the IC 95%)Very low1 studies

Context

Over 50% of IBD patients exhibit comorbid anxiety or depression, and available treatments rarely address both intestinal inflammation and neuropsychiatric symptoms simultaneously. Plant-derived nanovesicles (NPEVs) are emerging therapeutic candidates due to their oral stability and microbiota-modulating capacity. This study tests HNVs in a murine chronic colitis model focusing on the MGBA.

What the study showed

HNVs reduced anxiety- and depression-like behaviors in colitis mice across open field, elevated plus maze, and forced swim tests — absolute numbers and 95% CIs are not reported in the available text. Treatment preserved tight junction proteins (occludin, claudin), reduced pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), and decreased hippocampal immune cell infiltration. The BDNF/TrkB/GSK3β pathway was activated and tryptophan/5-HT metabolism was restored toward the healthy control profile.

How it was done

Preclinical experimental study in DSS-induced chronic colitis mice. HNVs were administered orally; assessments included behavioral assays, histology, microbiota analysis, cytokine quantification, hippocampal immunohistochemistry, and molecular biochemistry. Sample size, exact experiment duration, and formal randomization procedures are not detailed in the available extract.

Effect magnitude

The available text provides no effect sizes with 95% CIs (RR, OR, SMD, or MD) for any outcome; effects are described qualitatively as 'markedly attenuated,' precluding formal effect size quantification.

Risk of bias

Exclusively preclinical (mouse/DSS), with no human data — generalization is invalid. Absence of absolute numbers, 95% CIs, and formal effect sizes in the available extract precludes quantitative appraisal. No risk-of-bias tool (SYRCLE or ARRIVE) is mentioned; blinding and randomization are not explicitly described, raising detection and selection bias risk.

Interpretation limit

What this study does NOT prove

This study does NOT prove efficacy or safety in humans, nor does it establish definitive mechanistic causality between HNVs and MGBA modulation in clinical IBD. DSS murine model results have limited translational validity for human IBD.

In clinical practice

This study generates no applicable clinical recommendation. Clinicians should not recommend honeysuckle extracts or products for IBD or neuropsychiatric comorbidities based on this work. The study serves only to justify future translational investigation.

Limitations

Exclusively preclinical (mouse/DSS), with no human data — generalization is invalid. Absence of absolute numbers, 95% CIs, and formal effect sizes in the available extract precludes quantitative appraisal. No risk-of-bias tool (SYRCLE or ARRIVE) is mentioned; blinding and randomization are not explicitly described, raising detection and selection bias risk.

What is still missing

Non-human primate studies and subsequently phase I/II clinical trials in IBD patients with confirmed neuropsychiatric comorbidity are required before any therapeutic consideration.

Technical appendix

Version history

  • 1.0 · 2026-07-02 — Auto-generated under Evidence Standard v1.0
Source: DOI 10.7150/thno.132241 · 2026

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