Introduction

Irritable bowel syndrome (IBS) is characterized by abdominal pain or distension with the disorder of bowel habit and stool. It is believed that the changes of gut microbiota may play a major role in the occurrence and development of IBS. To date, few studies have focused on the clinical features and intestinal flora of IBS in the Tibetan population.

Aims & Methods

In this study, we aimed to compared the difference between the Tibets and Hans of IBS patients. This prospective single-center randomized controlled trial was designed and conducted in the Department of Gastroenterology, Hospital of Chengdu Office of People’s Government of Tibetan Autonomous Region, PR China. The study was approved by the Medical Ethics Committee (approval number: (2018) study No. 20). Patients meeting inclusion and exclusion criteria were grouped by their race to the Tibet group and the Han group. All enrolled patients were received conventional management. Besides, a simplified GSRS-based questionnaire, including five dimensions of IBS-related symptoms, was used to assess the severity of IBS. The stool samples of all participants were collected for the analysis of gut microbiota by the 16sRNA Illumina sequencing analysis.

Results

From August 2018 to January 2019, a total of 45 patients with IBS admitted to the were recruited in this study, including 20 Han and 25 Tibetan, aged from 27 to 74 years old. The baseline data for the two groups were comparable. No significant difference was found in the total symptom score of the simplified GSRS-based questionnaire between the Han and Tibetan groups. But the symptom components varied in each dimension（Figure 1）. According to symptom questionnaire, there was no significant difference in pain-related symptoms such as abdominal pain (13.93% vs 13.64%), pain frequency (13.43% vs 12.88%) and defecation pain (12.94% vs 11.36%) between the Tibetan and Han patients. However, it should be noted that Tibetans with IBS are more likely to suffer from bloating, and the proportion is significantly higher than that of the Han population(17.41% vs 9.09%, p<0.001). Moreover, shift of gut microbiota were showed between two groups. At the phylum level, the Tibet group had a significantly higher proportion of Bacteroidetes than the Han group (38.16±28.15% vs 17.28±13.72%, p=0.015). In total, 20 taxa were significantly different between the Tibet and the Han group and the top-10 representative taxa. There was a significant negative correlation between genus Blautia and bloating scores (Pearson r = -0.33, p=0.025)（Figure 2）.

Conclusion

The characteristics of Tibet patients differs from Han with IBS, not only in the clinical symptoms, but also in the characteristics of intestinal flora. Tibetans with IBS are more prone to bloating, which might due to the gut microbiota. The genus Blautia might play a role in this mechanism.

Introduction

The pathogenesis of irritable bowel syndrome with constipation (IBS-C) remains unclear. Several studies reported that gut dysbiosis had been observed in IBS patients. The treatment of IBS mostly focuses on symptomatic therapy. Acupuncture is one of the alternative therapies for IBS symptoms. However, the effects of acupuncture on symptoms and gut microbiota profiles of IBS-C patients are still unclear. The present study aimed to determine the alterations of the gut microbiota profiles between IBS-C patients and healthy subjects as well as to investigate the effect of electroacupuncture (EA) on the alterations of the profiles of gut microbiota and IBS symptoms in IBS-C patients.

Aims & Methods

We aim to determine the alterations of the gut-brain-microbiota axis between IBS-C patients and healthy subjects and to investigate the effect of electroacupuncture on the alterations of the gut-brain-microbiota axis in IBS-C patients. Thirty-two participants were enrolled in the study, including 16 healthy participants, as the control group and 16 IBS-C patients. Clinical data, blood, and fecal samples were collected from all participants. Then, 16 IBS-C patients were treated with EA nine times for 1 month. Clinical data, blood, and feces were collected in those IBS-C patients at 2-time points: after the end of EA and 1-month follow-up.

Results

Irritable bowel syndrome symptoms severity scale scores (IBS-SSS) and Irritable bowel syndrome quality of life (IBS-QoL) of IBS patients were significantly greater than the control group. There was no significant difference in cognition and depression scores in Hospital Anxiety and Depression Scale (HADs) between the control and the IBS-C groups. A significant increase in serum cortisol level in the IBS-C group was observed when compared to controls. Clinical outcomes of IBS symptoms were significantly improved after EA. These significances were also found in the 1-month follow-up. There was no significant change in serum cortisol levels following EA therapy. Regarding gut microbiota profiles, alpha diversity was not different between the four groups: control, IBS-C, after EA treatment, and 1-month follow-up. However, the beta diversity was significantly different among groups. The beta diversity used of PERMANOVA analysis showed a significant difference between the controls and IBS-C patients (PERMANOVA q-value < 0.05 in Bray-Curtis, Jaccard, and unweighted UniFrac distances). Immediately after EA therapy in IBS-C patients, the beta diversity showed no difference between pre- and post-treatment. Interestingly, the cluster of gut microbiota profiles shifted away from the IBS group and was similar to the control group after a 1-month follow-up.​

Conclusion

Our findings demonstrated the differences in profiles of gut microbiota profiles between IBS-C patients and healthy, and EA treatment showed the benefit of improving clinical outcomes and profiles of gut microbiota.

References

Chang L, Sundaresh S, Elliott J, Anton P, Baldi P, Licudine A, et al. Dysregulation of the hypothalamic‐pituitary‐adrenal (HPA) axis in irritable bowel syndrome. Neurogastroenterology & Motility. 2009.
Chen Y, Zhao Y, Luo D-n, et al. Electroacupuncture regulates disorders of gut-brain interaction by decreasing corticotropin-releasing factor in a rat model of IBS. Gastroenterology research and practice. 2019.
Tan L-h, Li K-g, Wu Y-y, et al. Effect of electroacupuncture at different acupoints on the expression of NMDA receptors in ACC and colon in IBS rats. Evidence-Based Complementary and Alternative Medicine. 2019.
Tap J, Derrien M, Törnblom H, Brazeilles R, Cools-Portier S, Doré J, et al. Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome. Gastroenterology. 2017.
Labus JS, Osadchiy V, Hsiao EY, et al. Evidence for an association of gut microbial Clostridia with brain functional connectivity and gastrointestinal sensorimotor function in patients with irritable bowel syndrome, based on tripartite network analysis. Microbiome. 2019.
Song Y-F, Pei L-X, Chen L, et al. Electroacupuncture relieves irritable bowel syndrome by regulating IL-18 and gut microbial dysbiosis in a trinitrobenzene sulfonic acid-induced post-inflammatory animal model. The American journal of Chinese medicine. 2020.
etc.

Disclosure

The authors declared that they have no conflicts of interest.

Introduction

Patients with IBS often report meal-related symptoms. These symptoms can negatively affect IBS-related quality of life, psychological health, and lead to food-avoidant behaviours¹. Developing our understanding of the impact of meal-related symptoms in IBS could lead to better treatment.

Aims & Methods

We aimed to compare the characteristics of patients with and without meal-related symptoms in IBS. Participants were recruited from the NIHR research register ContactME-IBS². We collected data for demographics, gastrointestinal symptoms^3,4,5, psychological health⁶, quality of life^7,8, and impact on work and daily activities⁹ using validated questionnaires among adults with IBS, as defined using the Rome IV criteria. We dichotomised the cohort according to whether they experienced meal-related symptoms, defined as being present ≥50% of the time, or not. We compared the characteristics of the two groups and used logistic regression to explore predictors of meal-related symptoms in IBS.

Results

Of 752 respondents with Rome IV IBS, 561 (74.6%) were affected by meal-related symptoms. 89.3% of individuals with meal-related symptoms were female vs 80.6% of those without (p =0.002). A significantly higher proportion of those with meal-related symptoms reported bloating or distension as their most troublesome symptom (31.2% vs 22.5%, p =0.008), and had a higher prevalence of functional dyspepsia, especially postprandial distress syndrome (49.1% vs 30.2%, p <0.001). Individuals affected by meal-related symptoms reported higher levels of gastrointestinal symptom-specific anxiety, had lower levels of IBS-related quality of life, and significantly higher levels of work productivity and activity impairment (p <0.001 for all analyses). Logistic regression analysis controlling for all other data showed that females (OR 2.3, 95% CI 1.30 - 4.08) and those with functional dyspepsia, both post-prandial distress syndrome (OR 2.0, 95% CI 1.3 - 3.3) and epigastric pain syndrome (OR 2.0, 95% CI 1.19 - 3.22), were more likely to report IBS meal-related symptoms. Conversely, IBS sufferers with abnormal depression scores were less likely to report meal-related symptoms (OR 0.4, 95% CI 0.20 - 0.72). This could reflect low mood leading to poor appetite. Overall, the model explained 22.8% of the variance of the data.


Table 1. Characteristics of Individuals with Rome IV IBS according to presence or absence of meal-related symptoms.

Conclusion

Individuals with Rome IV IBS who report meal-related symptoms experience significantly worse gastrointestinal symptom-specific anxiety and are more adversely affected at work compared to those without meal-related symptoms. These findings suggest that people with IBS and meal-related symptoms may benefit from early multidisciplinary treatment with dietary and psychological therapies.

References

1. Böhn L et al. Am J Gastroenterol. 2013 May;108(5):634-41.
2. ContactME-IBS. https://www.contactme-ibs.co.uk/. Accessed 23/4/2024.
3. Palsson OS et al. Gastroenterology. 2016;150:1481-91.
4. Whitehead WE et al. Rome III: The functional gastrointestinal disorders. Virginia: Degnon Associates Inc 2006. p. 835-53.
5. Labus JS et al. Aliment Pharmacol Ther. 2004;20:89-97
6. Spiller RC et al. Aliment Pharmacol Ther. 2010;32(6):811-20
7. Patrick DL et al. Dig Dis Sci. 1998;43(2):400-11.
8. Drossman DA et al. Am J Gastroenterol. 2000;95(4):999-1007.
9. Reilly MC et al. Aliment Pharmacol Ther. 2004;20(4):459-67

Introduction

Functional bowel disorders are characterized by the presence of altered bowel habits with or without abdominal pain.¹ Irritable bowel syndrome (IBS) is diagnosed based on recurrent abdominal pain; however, distinctions in the clinical phenotypes of IBS subtypes and other functional bowel disorders (FBDs), such as functional diarrhea (FD) and functional constipation (FC), remain underexplored.^2,3

Aims & Methods

Aims: This study aimed to characterize the clinical presentation of IBS with predominant constipation (IBS-D) and IBS with predominant diarrhea (IBS-C), differentiating them from FD and FC, while recognizing the overlapping symptoms and the continuum between these conditions. Additionally, we examined the prevalence of psychological disorders and extra-intestinal comorbidities and identified potential mediators linking IBS to anxiety and depression.
Methods: Using data from the Rome Foundation Global Epidemiology Study, we analyzed 54,127 participants across 26 countries, including 2,195 patients with IBS. Clinical, dietary and psychological characteristics were assessed using validated questionnaires. Subgroup analyses compared IBS subtypes with FBDs, while mediation analyses (using the PROCESS macro and Baron and Kenny's method⁴) identified mediators of IBS-psychological distress relationship.

Results

As compared to patients with IBS-D, patients with IBS-C reported more severe pain characteristics, including prolonged pain episodes (50.7% vs. 47.0% of the time with pain lasting >30 minutes, p=0.030) and pain episodes that escalated to a sustained severe intensity (44.2% vs. 38.1%, p=0.026), frequently accompanied by back pain (36.7% vs. 30.9%, p<0.001). Regular use of prescribed pain medications was also more frequent in IBS-C (39.3%) than IBS-D (31.8%, p=0.004). In contrast, as compared to IBS-C, patients with IBS-D showed a stronger association of pain with changes in stool consistency (70% vs. 60% of time with pain, p<0.001) and frequency (mean 61.3% vs. 57.8% of time with pain, p=0.008). These associations remained significant in multiple regression models, which confirmed that IBS-C is more strongly linked to prolonged and escalating pain episodes, while IBS-D is more closely linked to pain associated with changes in stool frequency and consistency. As compared to FD, IBS-D patients reported greater dissatisfaction with bowel function (57.3±28.4 vs. 44.2±29.8, p<0.001), and more frequent loose stools (without constipation treatments) (60.0% vs. 50.0% of bowel movements, p<0.001), particularly after meals (60.0% vs. 40.0% of loose stools, p<0.001). IBS-C shows more severe constipation-related symptoms compared to FC (p<0.001). Mediation analyses revealed that concerns about bowel function, embarrassment discussing it, and work-related impairments partially mediated the relationship between IBS and psychological distress.

Conclusion

IBS-C is associated with more severe pain episodes, including prolonged and escalating pain, while in IBS-D pain is more strongly linked to bowel habit changes. These findings highlight the distinct clinical profiles of IBS subtypes and emphasize the need for personalized, multimodal management strategies. Identifying mediators of psychological distress in IBS can guide targeted interventions, improving patient outcomes.

References

1. Lacy, B. E. et al. Bowel Disorders. Gastroenterology (2016) doi:10.1053/j.gastro.2016.02.031.
2. Savarino, E. et al. Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility. United European Gastroenterol J 10, 556–584 (2022).
3. Mearin, F. et al. Clinical Practice Guideline: Irritable bowel syndrome with constipation and functional constipation in the adult. Revista espanola de enfermedades digestivas 108, 332–63 (2016).
4. Baron, R. M. & Kenny, D. A. The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol 51, 1173–82 (1986).

Introduction

Irritable bowel syndrome (IBS) is a complex multifactorial disorder characterized by recurrent abdominal pain associated with defecation or a change in bowel habits. Patients with IBS often complain of extra-intestinal symptoms resulting in impaired related quality of life. Growing evidence support the hypothesis that intestinal barrier dysfunction has a central role in the pathophysiology of IBS being the interface between the gut lumen and the deeper intestinal layers as well as the brain.

Aims & Methods

The aims of this study were: to characterize the epithelial and vascular barriers; to correlate molecular, morphological and functional aspects of epithelial and vascular barriers with IBS symptoms. 66 healthy subjects (AC) and 223 patients with IBS (112 IBS-D, 58 IBS-C and 53 IBS-M) were enrolled in the study. Rome IV criteria, Bowel disease questionnaire, Short Form 36, Hospital Anxiety Depression Scale were used to phenotype patients. Sugar test was used to evaluate in vivo permeability. The vascular barrier was characterized by using immunohistochemistry, western blot and electron microscopy. Vascular permeability was evaluated by assessing two markers: plasmalemma vesicle–associated protein-1 (PV1) and vascular endothelial cadherin (VEC). A translational model based on Caco-2 cells or HUVEC was used to evaluate permeability changes induced by mediators spontaneously released by mucosal biopsies and to highlight the underlying molecular mechanisms. Correlation analyses have been performed among experimental and clinical data.

Results

Compared to AC, lactulose (P<0.05), sucralose (P<0.01), sucrose (P<0.01) excretion and the L/M ratio (P<0.01) were significantly increased in IBS patients. Soluble mediators released by mucosal biopsies of IBS patients increased Caco-2 permeability compared to AC mediators (P<0.05) via a down-regulation of tight junction gene expression. Blood vessels were significantly increased by 1.5 fold in the colonic mucosa of IBS patients compared to AC (P<0.01). PV1 expression was increased (P<0.01) while VEC expression was decreased in the colonic mucosa of IBS group compared to AC (P<0.05). IBS mucosal mediators increased HUVEC permeability compared to AC mediators. The HUVEC changes associated with IBS samples were mediated by a protease-activated receptor (PAR)2 dependent mechanism resulting in VEC down-regulation. Significant correlations emerged among permeability changes and intestinal, extra-intestinal symptoms and health-related quality of life reported by IBS patients.

Conclusion

Epithelial and vascular barriers are compromised in IBS and are likely involved in symptom development.

Disclosure

Nothing to disclose

Introduction

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by abdominal pain and changes in bowel habits. Small intestinal bacterial overgrowth (SIBO) refers to a group of gastrointestinal syndromes caused by an excessive number of bacteria in the small intestine. Up to now, the relationship between IBS and SIBO remains contentious. So we set out to investigate the differences between these two conditions.

Aims & Methods

Participants who met the Rome III diagnostic criteria for IBS and had a negative lactulose hydrogen and methane breath test (LHMBT) were diagnosed with IBS. Those who presented with gastrointestinal symptoms and had a positive LHMBT were diagnosed with SIBO. Overlapping cases were excluded. Participants who had a negative LHMBT and no significant abdominal symptoms were classified as healthy controls (HC). All participants were instructed to provide fecal samples for 16S rRNA sequencing.

Results

Our results showed that a history of enteritis was more common in IBS patients, and the severity of gastrointestinal symptoms was significantly higher in IBS and SIBO groups compared to healthy controls. IBS patients also reported more severe symptoms than SIBO. Additionally, IBS patients were more affected by their symptoms, while the SIBO group reported more dissatisfaction with bowel habits. We observed differences in dietary intake between the groups, with IBS patients having the highest total energy and protein intake, and the lowest dietary fiber intake. SIBO patients had higher fat intake and significantly lower carbohydrate intake compared to the other two groups. Regarding the fecal microbiome, both IBS and SIBO patients had higher structural diversity and lower functional diversity than the HC group. The abundance of Firmicutes/Bacteroidetes in the IBS group was significantly higher than in the other two groups. Our analyses indicated that the fecal microbiome could significantly distinguish the three groups, and specific bacterial species were associated with different symptoms in each group. In SIBO, Thalassospira and Christensenellaceae_group were associated with intestinal motility abnormalities, while Ruminococcaceae_group, Butyricimonas, and Oscillospira were associated with gas production. In the IBS group, Klebsiella and Mitsuokella were associated with abdominal pain, and other bacteria such as Escherichia_Shigella and Enterobacter were generally associated with enteritis infection, abdominal pain, and diarrhea. We also found that the predicted KEGG pathways were enriched in various nutrient metabolism pathways, with potential implications for elevated blood folate levels and vitamin B12 deficiency in SIBO patients.Protein bacterial motility and biofilm formation_ Escherichia coli, were mainly enhanced in IBS, and these functions were related to the mucosal barrier damage.

Conclusion

Our study shows that although IBS and SIBO share similar symptom spectra, they may be two distinct diseases. Despite the potential differences in the fecal flora of small intestinal flora in SIBO group, significant differences were found between IBS and SIBO in terms of clinical phenotype and fecal microbiome. Further exclusion of SIBO using lactulose hydrogen and methane breath testing in patients who meet the diagnostic criteria for IBS is warranted, as the differences suggest that different treatment strategies may be needed for these two populations. Future studies are needed to explore the underlying mechanisms and potential therapies for these conditions, which may ultimately benefit patients with IBS and SIBO.

References

1. Quigley EMM, Murray JA, Pimentel M. AGA Clinical Practice Update on Small Intestinal Bacterial Overgrowth: Expert Review. Gastroenterology. 2020; 159(4):1526-1532. DOI: 10.1053/j.gastro.2020.06.090
2. Bushyhead D, Quigley EMM. Small Intestinal Bacterial Overgrowth-Pathophysiology and Its Implications for Definition and Management. Gastroenterology. 2022; 163(3):593-607. DOI: 10.1053/j.gastro.2022.04.002
3. Ghoshal UC, Nehra A, Mathur A, Rai S. A meta-analysis on small intestinal bacterial overgrowth in patients with different subtypes of irritable bowel syndrome. J Gastroenterol Hepatol. 2020; 35(6):922-931. DOI: 10.1111/jgh.14938
4. Mearin F,Lacy BE,Chang L, et al. BowelDisorders[J].Gastroenterology,2016;150;1393-1407.
5. Zhu L, Huang D, Shi L, et al.Intestinal symptoms and psychological factors jointly affect quality of life of patients with irritable bowel syndrome with diarrhea.Health
Qual Life Outcomes. 2015;13:49.
6. Sperber AD,Dumitrascu D, Fukudo S, et al.Gut 2017;66:1075–1082
7. Jindong Zhang, Jiao Liu, Shiwei Zhu, Ben Wang, Qiong Jia, Qihua He, Lijin Song, Yuan Fang, Baoli Zhu, Liping Duan. Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation. Acta Pharmacologica Sinica，Accepted 2020