ArticlePloS one2014
Relationship between vagal tone, cortisol, TNF-alpha, epinephrine and negative affects in Crohn's disease and irritable bowel syndrome.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06553053 (Acupuncture Reduces Relapse in Patients With Crohn's Disease), which is not on this map. Cited by 103 papers, 5 of them syntheses that pooled it.
What it found
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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.
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.
Acupuncture Reduces Relapse in Patients With Crohn's Disease: a Superiority Trial
Who cites it
103 citing papers in PubMed, 5 syntheses or guidelines pooled it, 205 citations in OpenAlex.
- Serological and faecal markers of irritable bowel syndrome: a systematic review and meta-analysis.EBioMedicine · 2026Pooled it
- Heart Rate Variability-An Index of the Efficacy of Complementary Therapies in Irritable Bowel Syndrome: A Systematic Review.Nutrients · 2022Pooled it
- Alterations in Heart Rate Variability Associated With Irritable Bowel Syndrome or Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.Clinical and translational gastroenterology · 2020Pooled it
- Heart rate variability and inflammatory bowel disease in humans: A systematic review and meta-analysis.Medicine · 2020Pooled it
- Salivary Biomarkers for Diagnosis of Inflammatory Bowel Diseases: A Systematic Review.International journal of molecular sciences · 2020Pooled it
- The heart knows best: baseline heart rate variability as guide to transcutaneous auricular vagus nerve stimulation in depression.Translational psychiatry · 2025Trial
- The effect of pyridostigmine on small intestinal bacterial overgrowth (SIBO) and plasma inflammatory biomarkers in HIV-associated autonomic neuropathies.Journal of neurovirology · 2019Trial
- Auricular Vagus Nerve Stimulation in Inflammatory Bowel Disease: Mechanistic Insights and Biomarker-Based Evaluation of Therapeutic Response.International journal of molecular sciences · 2026Review
- Context-Dependent Modulation of Epithelial Barrier Integrity and Intestinal Permeability by Transcutaneous Auricular Vagus Nerve Stimulation in Two Preclinical Models Mimicking Ulcerative Colitis and Crohn's Disease: A Descriptive Analysis.International journal of molecular sciences · 2026Article
- Autonomic and neural responses to varying transcutaneous cervical electrical stimulation parameters.Bioelectronic medicine · 2026Article
- Article
- Vagus nerve stimulation in Crohn's disease: long-term outcomes, mechanistic insights, and the promise of non-invasive approaches.Bioelectronic medicine · 2026Article
- Current Perspectives on the Inflammatory Bowel Disease Pathogenesis of Microbiota and the Gut-Brain Axis, and Emerging Therapeutics.Biomedicines · 2026Review
- Mechanisms of chronic abdominal pain in inflammatory bowel disease and implications for treatment.Nature reviews. Gastroenterology & hepatology · 2026Review
- Microglia alter autonomic nucleus neuronal activation after peripheral cytokine challenge.American journal of physiology. Cell physiology · 2026Article
- Noninvasive electrical neuromodulation involving vagus nerve mechanism for functional constipation and irritable bowel syndrome with constipation.Therapeutic advances in gastroenterology · 2026Review
- Neuroimmune interactions in inflammatory bowel disease: Role of intestinal macrophages and the cholinergic pathway.World journal of gastroenterology · 2025Review
- Role of physical exercise, vagal nerve stimulation, and vagotomy in inflammatory bowel disease.World journal of gastroenterology · 2025Review
- Efficacy and mechanisms of neuromodulation in the treatment of irritable bowel syndrome.Bioelectronic medicine · 2025Review
- Enteric neuropathy and the vagus nerve: Therapeutic implications.Neurogastroenterology and motility · 2025Review
43 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Crohn's disease (CD) and irritable bowel syndrome (IBS) involve brain-gut dysfunctions where vagus nerve is an important component. The aim of this work was to study the association between vagal tone and markers of stress and inflammation in patients with CD or IBS compared to healthy subjects (controls). The study was performed in 73 subjects (26 controls, 21 CD in remission and 26 IBS patients). The day prior to the experiment, salivary cortisol was measured at 8:00 AM and 10:00 PM. The day of the experiment, subjects completed questionnaires for anxiety (STAI) and depressive symptoms (CES-D). After 30 min of rest, ECG was recorded for heart rate variability (HRV) analysis. Plasma cortisol, epinephrine, norepinephrine, TNF-alpha and IL-6 were measured in blood samples taken at the end of ECG recording. Compared with controls, CD and IBS patients had higher scores of state-anxiety and depressive symptomatology. A subgroup classification based on HRV-normalized high frequency band (HFnu) as a marker of vagal tone, showed that control subjects with high vagal tone had significantly lower evening salivary cortisol levels than subjects with low vagal tone. Such an effect was not observed in CD and IBS patients. Moreover, an inverse association (r = -0.48; p<0.05) was observed between the vagal tone and TNF-alpha level in CD patients exclusively. In contrast, in IBS patients, vagal tone was inversely correlated with plasma epinephrine (r = -0.39; p<0.05). No relationship was observed between vagal tone and IL-6, norepinephrine or negative affects (anxiety and depressive symptomatology) in any group. In conclusion, these data argue for an imbalance between the hypothalamus-pituitary-adrenal axis and the vagal tone in CD and IBS patients. Furthermore, they highlight the specific homeostatic link between vagal tone and TNF-alpha in CD and epinephrine in IBS and argue for the relevance of vagus nerve reinforcement interventions in those diseases.
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Registered trials
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.