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

Studies have shown that adults with irritable bowel syndrome (IBS) may be associated with anxiety, mood disorders, chronic headache, and other neuropsychiatric conditions. This growing body of evidence can allude to a possible bidirectional gut-brain connection. While adolescence is the age when both IBS and neuropsychiatric illnesses often first manifest, this population remains under-studied.

Aims & Methods

We aim to assess the association between the presence of irritable bowel syndrome (IBS) and neurologic and psychiatric disorders in a nationwide cohort of adolescents. This cross-sectional study included all adolescents aged 16-21 who underwent mandatory medical evaluations as part of their conscription between 2000-2021. All individuals completed comprehensive medical interviews. Suspected diagnoses prompted referral to board-certified specialists for confirmation and severity grading based on predefined criteria. IBS was diagnosed according to the Rome II-IV criteria by a certified gastroenterologist.
Neurologic disorders included attention-deficit/hyperactivity disorder [ADHD], epilepsy, chronic headache, sleep disorders. Psychiatric disorders included psychotic, personality, general anxiety disorder [GAD], non-combat post-traumatic stress disorder [PTSD], mood, dissociative, and eating disorders. Each diagnosis was classified by severity (mild, moderate, severe). Unadjusted and multivariate-adjusted logistic regression models were fitted to estimate odds ratios (ORs) for associations with IBS. The adjusted models were accounted for age, sex, intelligence score, body mass index (BMI), socioeconomic status (SES), education, country of origin, and any concurrent neuropsychiatric diagnoses.

Results

The study included 1,561,717 adolescents (666,442 [42%] women, mean age 17.4 ± 1.4 years), of whom 7,230 (0.46%) were diagnosed with IBS (4,778 mild; 1,948 moderate; 504 severe). Neurologic disorders were present in 1,661 (23.0%) and 143,348 (9.2%) of those with and without IBS, respectively. The respective numbers of people with psychiatric disorders were 773 (10.7%) and 49,889 (3.2%). In multivariable adjusted models, those with IBS were more likely to have chronic headache (aOR 4.7, 95% CI: 4.4-5.1), GAD (aOR 3.6, 95% CI: 3.2-3.9), eating disorders (aOR 2.6, 95% CI: 1.9-3.5), mood disorders (aOR 2.5, 95% CI: 2.1-3.1), personality disorders (aOR 2.5, 95% CI: 2.1-2.9), and dissociative disorders (aOR 19.1, 95% CI: 12.5-28.9). Patients with severe IBS (n=504) were independently associated with the presence of at least one severe neurologic (aOR 2.9, 95% CI: 1.2-7.1) or psychiatric disorder (aOR 3.8, 95% CI: 2.6-5.4).

Conclusion

In this large nationwide cohort, adolescents with IBS were more likely to have several tested neurologic and psychiatric disorders, compared to those without IBS. Longitudinal studies are needed to explore the directionality and long-term implications of these associations.

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.

Introduction

Inflammatory Bowel Diseases (IBD) require lifelong treatment and patient monitoring. Current predictors of relapse and therapeutic success have limitations, mostly invasive, time-consuming, and expensive. The faecal biomarker can help to monitor the disease activity and therapeutic response by simple and non-invasively. Faecal Calprotectin (FC) is the gold-standard, but it has many disadvantages. We previously described that the correlation between the faecal Plasminogen activator inhibitor type 1 (PAI-1) (FP) level and the endoscopic activity and therapeutic response promote that it could be used as a novel non-invasive faecal biomarker in IBD diagnosis. Moreover, the faecal PAI-1 protein level is stable at room temperature and 4°C.

Aims & Methods

To observe the exact faecal biomarker potential, we aimed to define the FP level of IBD patients and subjects with other gastrointestinal (GI) diseases and compare it with the FC. Faecal samples were collected from 128 patients with IBD (CD-active: 18, CD-inactive: 10, UC-active: 20, UC-inactive: 10) and other GI diseases [colorectal cancer (CRC): 20, diverticulosis [DIV]: 21, irritable bowel syndrome [IBS]: 10, adenoma: 10) and 9 healthy subjects. ELISA method was applied to define FP level, and it was validated for stool samples by us and 0.5 ng/g PAI-1 level was defined as the cut-off value. For FC observation diagnostic FC ELISA kit (Orgentec) was used. 50 mg/g cut-off value was applied at FC. Confusion matrix analysis was utilized to define Youden-index, positive predictive value (PPV), negative predictive value (NPV), accuracy, specificity, and sensitivity of the measured values.

Results

FP level was significantly higher in patients with active IBD compared to inactive and non-IBD subjects (0.64 vs 0.0 ng/g, p<0.0001). No significant differences were observed between CD-active and UC-active groups (0.46 vs 0.79 ng/g, p=0.65). In addition, FP concentrations were significantly increased in active IBD (0.76 pg/g) patients compared to inactive IBD (0.0 pg/g, p=0.0001), CRC (0.11 ng/g, p=0.02), DIV (0.05 ng/g, p=0.001), IBS (0.0 ng/g, p<0.0001), adenoma (0.0 ng/g, p<0.0001), and healthy (0.0 ng/g, p=0.0002) subjects. However, FC showed the same pattern as FP, except at the CRC, adenoma and DIV. In these groups, there were no significant differences compared to the active IBD (487.4 mg/g) subjects (vs CRC: 147.1 mg/g, p=0.09; p=; adenoma: 159.8, p=0.056. Confusion matrix analysis defined high specificity (83.5%) and moderate sensitivity (57.9%) values (TP: 22, FP: 14, FN: 17, TN: 71, PPV: 0.61, NPV: 0.816) at the FP measurements. Nevertheless, at FC levels 35.3% specificity and 94.7% sensitivity were measured (TP: 36, FP: 55, FN: 2, TN: 30, PPV: 0.396, NPV: 0.938). Calculated Youden-index was higher at the FP (0.41) compared to the FC (0.3). On the other hand, the accuracy of the FP is 75.6% and the FC is 53.6%. Based on the results of all FP levels measured (N=299) so far, the calculated values were specificity: 78%, sensitivity: 62%, PPV: 0.63, NPV: 0.78, Youden-index: 0.4, accuracy: 72.3%.

Conclusion

Our results suggest that the FP level selectively increased in the active IBD and discriminated more specifically from the other GI diseases compared to the FC. However, the sensitivity was lower, but it was improved by the increasing patient numbers at the pooled FP levels. Thus, the FP level could be useful in the diagnosis of IBD independently or combined with FC.

References

Jójárt B, Resál T, Kata D, Molnár T, Bacsur P, Szabó V, Varga Á, Szántó KJ, Pallagi P, Földesi I, Molnár T, Maléth J, Farkas K. Plasminogen Activator Inhibitor 1 Is a Novel Faecal Biomarker for Monitoring Disease Activity and Therapeutic Response in Inflammatory Bowel Diseases. J Crohns Colitis. 2024 Mar 1;18(3):392-405. doi: 10.1093/ecco-jcc/jjad160. PMID: 37751311; PMCID: PMC10906952.

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 chronic gut-brain disorder that can be responsabil for a variety of uncomfortable gastrointestinal symptoms (laid out in the Rome Criteria) that can reduce quality of life. Although the precise mechanism remains unknown, recent research suggests that an imbalance in intestinal microbiota and a dysfunctional gut-brain axis may be involved in the development of IBS. Because of this, methods to restore the microbiota have been explored as treatment for this condition.

Aims & Methods

Randomized placebo controlled trial 180 patients: active group (probiotic formula, 3g/day- 92, placebo group – 88. men and women aged 24 to 75 who met the Rome IV criteria. One sachet probiotic (3 g) contains 7.5 billion bacteria: Lactobacillus casei W56, Lactococcus lactis W19, Lactobacillus acidophilus W22, Bifidobacterium lactis W52, Lactobacillus paracasei W20 Lactobacillus plantarum W62, Bifidobacterium lactis W51, Bifidobacterium bifidum W23, Lactobacillus salivarius W24. Assessments were made at 4, 8, 12 weeks. All patients agreed to maintain their lifestyle behaviors during their participation in the study. Exclusion criteria: chronic gastrointestinal condition (other than IBS), including inflammatory bowel disease, lactose intolerance, celiac disease, diabetes, neoplasms.Patients have complete weekly data on stool frequency and consistency (Boston scale) and intensity of IBS symptoms (abdominal pain/discomfort, bloating, flatulence/borborygmi, and difficulty defecating) on a Likert scale of 0 (absent) to 7 (severe). Participants completed an IBS-specific quality of life questionnaire (IBS-QoL) at randomization (V1), fallow-up (V2) and at the end of the intervention (V3). Primary endpoint was mean weekly scores of gastrointestinal symptoms. Responders of abdominal pain were defined as subjects who experienced a reduction of at least 30% of the mean daily abdominal score reported at baseline (week 0). Secondary endpoints were the total AUC (W0-W12) of abdominal symptoms (abdominal pain, bloating and flatulence/borborygmi).

Results

​There is a significant reduction in abdominal pain and bloating scores trough all 12 weeks of supplementation versus placebo. A higher overall IBS-QOL score, indicative of better QOL was reported at the end of the intervention (specially for interference with activity P=0.05, body image P=0.040, food avoidance P=0.03)

Conclusion

​The probiotic treatment provides statistically significant and clinically relevant benefits for individuals with IBS. Improves gastrointestinal symptoms and quality of life in IBS patient

References

Rome IV criteria-Rome Foundation