Introduction

Non-invasive biomarkers that enable accurate diagnosis, patient stratification, and therapy monitoring in irritable bowel syndrome (IBS) are still lacking in clinical practice. Volatile organic compounds (VOCs) produced by the host metabolism, inflammatory processes, and the gut microbiota are present in exhaled breath and have recently gained attention as promising biomarker candidates. Prior research (Van Malderen et al. (2020)) demonstrated that breath VOC profiling could accurately distinguish IBS patients from healthy controls using multicapillary column/ion‑mobility spectrometry (MCC/IMS).

Aims & Methods

The present study aimed to assess the potential of high-resolution gas chromatography-quadrupole time‑of‑flight mass spectrometry (GC-QTOF-MS) profiling of breath VOCs to define distinct compound classes that enhance the mechanistic understanding of breath-based biomarkers in IBS. To this end, breath samples from 12 IBS patients and 11 healthy controls were collected, together with matched ambient air samples and were analyzed using GC-QTOF-MS. Breath samples were corrected by background subtraction and least‑absolute‑shrinkage‑and‑selection‑operator (LASSO) regression was applied with leave‑one‑out cross‑validation (LOOCV) to identify discriminative VOC signatures. The feature set was subsequently filtered to exclude sporadically detected VOCs and compounds of exogenous (non-host) origin. Finally, the remaining VOCs were mapped to putative pathways.

Results

IBS patients had a mean ± SD age of 36 ± 15.3 years, compared with 56 ± 15.4 for the healthy controls. The male-to-female ratio was 3:9 in the IBS cohort and 5:6 among the healthy controls. Within the IBS group, 7 patients had diarrhea-predominant IBS, 4 had constipation-predominant IBS, and 1 had mixed-type IBS. The LASSO regression model, validated with LOOCV, demonstrated high discriminative performance in differentiating IBS patients from healthy controls, with the corresponding model metrics in Table 1. Furthermore, the feature selection identified a panel of discriminative VOCs - predominantly alkanes, aldehydes, and ketones - that were up-regulated in the IBS breath profiles. These elevated compound classes could putatively be linked to mechanisms relevant to IBS pathophysiology, including altered microbial metabolism, increased oxidative stress, and low-grade inflammation.

Table 1: Model metrics

Conclusion

Volatomic breath profiling in IBS, shows great potential for discriminating IBS from healthy controls and for defining clinically relevant biomarkers composed of specific VOCs. Nonetheless, the limited sample size might risk model overfitting and introduces uncertainty in the estimates. Further research including larger, confounder-controlled cohorts is necessary, along with the targeted validation of the identified VOCs to further confirm their mechanistic role in IBS.

References

Van Malderen K, Hanning N, Lambrechts H, Haverhals T, Van Marcke S, Ceuleers H, De Man JG, De Winter BY, Lamote K, De Schepper HU. Volatile organic compound profiling as a potential biomarker in irritable bowel syndrome: A feasibility study. Front Med (Lausanne). 2022 Aug 4;9:960000. doi: 10.3389/fmed.2022.960000. PMID: 35991639; PMCID: PMC9388331.

Introduction

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction affecting 5 to 10% of the population, combining chronic abdominal pain and altered bowel transit. Its varied and complex mechanisms make management difficult and can be responsible for impaired quality of life. Patient education is recommended for managing chronic diseases. As part of a patient education program, the first step is to assess patients' knowledge and needs by conducting a shared educational assessment. Experiments conducted in various countries have shown that therapeutic patient education (TPE) can be effective, reducing severity, improving quality of life, and reducing care seeking. These studies have also shown that patients often have a lack of knowledge and/or misconceptions about IBS (1).

Aims & Methods

This study aimed to assess the baseline knowledge level of patients enrolled in a patient education program. Patients with IBS were selected for participation in a TPE program following a multidisciplinary day hospital for IBS. All patients had to have seen a general practitioner and/or a gastroenterologist outside the team without sufficient improvement in their condition. The TPE was based on a document developed in collaboration with a patient organisation (APSSII). This program was divided into five 1-hour sessions (training and discussion time) conducted by different professionals (neurogastroenterologists, clinical psychologist, dietitian) covering the following points:
1) understanding my illness (epidemiology, diagnosis, mechanisms),
2) talking about my illness and expressing my needs (interaction with loved ones, work, doctor, school, rights and support);
3) organizing my daily life, improving my quality of life (impact of IBS on QoL, work, exercise, intimate life);
4) taking advantage of different treatments and care options (placebo, adverse effects, symptomatic and long-term treatment, alternative treatments);
5) the role of eating and diets (balanced diet, lactose-free, gluten-free, low-FODMAP, food allergies, risks of diets). Before the start of each session, questionnaires testing participants' knowledge on the session topic were completed.

Results

From November 2023 to September 2024, 135 questionnaires completed by 43 patients with IBS were included. 70% were women, mean age 45 ± 18 years, subtypes based on IBS transit: IBS-C 55%, IBS-D 33%, IBS-M 12%, with a mean severity (IBS-SSS) of 331 ± 72 points, EQ5D health score of 50 ± 21. Among the most common misconceptions, 25% believed that a diagnosis by endoscopy was possible, 48% believed the disease could be complicated by IBD, and 13% by colon cancer. Regarding treatments, 11% of patients believed that the placebo effect only concerned medications, 58% believed that faecal microbiota transplantation could currently be offered in clinical routine for IBS care, 78% believed that hypnotherapy was only effective if you believe in it, and 68% believed that multi-strain probiotics were more effective than single-strain ones.

Conclusion

This study, conducted in France on patients with moderate or severe forms of IBS, shows a highly variable level of knowledge about their disease depending on the questions, with some significant misconceptions that need to be addressed. These results justify the implementation of therapeutic education for these patients. A study is underway to verify the improvement in patients' knowledge and the existence of a positive impact of this strategy on symptom severity and quality of life.

References

(1) Halpert et al. What Patients Know About Irritable Bowel Syndrome (IBS) and What They Would Like to Know. National Survey on Patient Educational Needs in IBS and Development and Validation of the Patient Educational Needs Questionnaire (PEQ). Am J Gastroenterol 2007; 102:1972-82.

Disclosure

Nothing to disclose

Introduction

The densities of stem cells and their progenitors, and enteroendocrine cells are lower in IBS patients than healthy subjects.^1,2 IBS patients also exhibit submucosal low-grade inflammation.³

Aims & Methods

This study investigated the possible mechanisms underlying the effects of FMT in IBS patients included in a previous study from our group that showed high and long-term efficacy. Ninety-three patients who participated in our previous study were investigated: placebo group (24 patients), the groups that received 30g (47patients) or 60g (22 patients) donor`s transplant. The patients underwent sigmoidoscopy with biopsies, provided faecal samples, and completed IBS-symptom severity score (IBS-SSS), Fatigue Assessment Scale (FAS), and IBS Quality of Life questionnaires at the baseline and at 1 month after FMT. Sections from the biopsy samples were immune-stained for Musahi-1 (marker for stem cells and in their early progeny), neurogenin 3 (marker for early endocrine cell progenitors), chromogranin A (general marker for enteroendocrine cells), serotonin, peptide YY (PYY), glucagon-like peptide 1, GLP-1, pancreatic polypeptide, somatostatin, CD 45 (common marker for immune cells), B lymphocytes, T lymphocytes. NK cells, monocytes, macrophages, myeloid cells, and mast cells. The cell densities were quantified by computerized image analysis. Faecal short chain fatty acids (SCFAs) were measured by gas chromatography, and faecal bacteria by 16S rRNA PCR DNA amplification covering variable regions V3–V9.

Results

The densities of Musashi-1, neurogenin 3, chromogranin A, serotonin, PYY, and GLP-1 expressing cells increased significantly following FMT in patients who received 30g, or 60g transplant, but not in the placebo group. The densities of Musashi-1, neurogenin 3, chromogranin A, serotonin, and GLP-1 expressing cells correlated inversely with IBS-SSS total scores (r=-0.4, P<0.0001; r= -0.2, P=0.007; r=- 0.3, P<0.0001; r=-0.2, P=004; r=-0.4, P<0.0001, respectively). The densities of Musashi-1, chromogranin A, and GLP-1 also correlated inversely with FAS total scores (r=-0.2, P=0.01; r= -0.2, P=0.002; r=- 0.3, P=0.0009, respectively). The density of PYY cells did not correlate with either IBS-SSS or FAS scores. The densities of total submucosal immune cells, and mast cells decreased significantly after FMT in patients treated with 30g, or 60g donor´s faeces, but were unchanged in the placebo group. The densities of these cells were correlated positively with IBS-SSS total scores (r=0.4, P<0.0001; r=0.5, P<0.0001, respectively), and the total immune cells correlated with FAS total scores (r=0.3, P=0.0002). The levels of butyric acid increased significantly following FMT in the 30g and 60g treated groups, but not in the placebo group. The faecal levels of butyric acid were inversely correlated with IBS-SSS (r=-04. P<0.0001), and FAS (r=-0.3, P<0.0001) total scores. Among the bacteria that their abundance increased significantly in IBS patients that received FMT were Alistipes, Faecalibacterium prausnitzii, Eubacterium biforme and Lactobacillus spp.

Conclusion

Stem cells, enteroendocrine progenitor, serotonin, and GLP-1cells, as well as low-grade inflammation appear to play a significant role in IBS symptom manifestation and that FMT effect most probably is due to restoring the abnormality in them. The present observations suggest potential new treatments for IBS such as transplantation of epithelial organoids containing stem cells, GLP-1 agonist, low-dose anti-inflammatory drugs, pharmacological drugs to control mast cell function³, and sodium butyrate.

References

1-El-Salhy M. Possible role of intestinal stem cells in the pathophysiology of irritable bowel syndrome. World J Gastroenterol 2020;26:1427-1438.
2-El-Salhy M, Hausken T, Gilja OH, et al. The possible role of gastrointestinal endocrine cells in the pathophysiology of irritable bowel syndrome. Expert Rev Gastroenterol Hepatol 2017;11:139-148.
3-Barbara G, Stanghellini V, De Giorgio R, et al. Functional gastrointestinal disorders and mast cells: implications for therapy. Neurogastroenterol Motil 2006;18:6-17.

Disclosure

Nothing to disclose

Introduction

Irritable bowel syndrome (IBS) has a profound impact on health-related quality of life. Increasing evidence suggests psychological factors have a large impact in the development and course of IBS, and in particular quality of life, with large individual heterogeneity. This observational study aims to investigate the influence of personality traits using the Big Five Inventory (BFI) and examine their associations with abdominal pain, general and gastrointestinal-specific anxiety, and quality of life in patients with IBS.

Aims & Methods

Data from a large observational study in patients with IBS (Rome III criteria) was used, in which patients completed questionnaires with regards to personality traits (BFI-44), symptom severity, general anxiety, GI-specific anxiety, and quality of life. Multivariable regression models and a network correlation analysis were used to determine underlying associations.

Results

194 patients were included for analysis (74.7% female, mean age 51.36 years). There was a positive association of neuroticism to GI-specific anxiety (B 7.234, P = 0.040) and general anxiety (B 0.954, P = 0.040) with a strong negative association to mental quality of life (B – 3.576, P = 0.007). In addition, a strong negative association of agreeableness to mental quality of life was found (B – 4.266, P = 0.001). Although there were no significant associations of personality traits to abdominal pain, positive associations were found regarding general anxiety (B 6.304, p < 0.001) and GI-specific anxiety (B 0.034, P <0.001) of abdominal pain. There were no associations found with regards to the other personality traits openness, conscientiousness or extroversion.

Conclusion

IBS patients with a higher level of neuroticism were more likely to experience higher levels of GI-specific and general anxiety. The trait neuroticism and/or agreeableness was more likely to have a significant lower mental quality of life in IBS. These findings emphasize the contribution of personality traits in the pathophysiology and course of IBS, pleading for a more personalized approach in patient management.