Introduction

It is known that the irregular rhythm of defecation in the form of constipation increases the risk of colorectal cancer by almost 2 times [1-3]. Constipation increases the risk of cardiovascular mortality by 39% - 56% [4 - 6]. Irregular bowel habit increases the risk of obesity, stroke and comorbidity [6 - 8]. However, the effect of irregular bowel habits on the risk of anxiety and depression remains poorly understood.

Aims & Methods

The aim was to screen irregularity of the circadian rhythm of defecation and the occurrence of anxiety and depression in cardiological patients.
We used the method of "Chronoenterography" – weekly monitoring of the regularity of the rhythm of defecation and the study of the level of Anxiety and Depression using a special questionnaire HADS and took into account the level of quality of life (SF-36). 66 patients (38 women and 28 men aged 40-79 years) who were hospitalized for metabolic syndrome in a cardiology clinic were examined.

Results

Irregular Bowel Habit (IBH) occurred in 65% of the examined patients (in 43 out of 66). Regular Bowel Habit (RBH) was detected in 35% of patients (in 23 out of 66). 3 stages of IBH have been identified. The first stage (mild, 5-6 bm/w) occurred in 61% of patients. The second stage (moderate, 3-4 bm/w) – in 30% of patients. The third stage of IBH (severe, 1-2 bm/w) – in 9% of patients. It should be noted that the first two stages of IBH were almost 10 times more common than the third (constipation stage). Anxiety and depression were not detected in patients with RBH. Subclinical anxiety in patients with mild stage of IBH was detected in 12% of cases, in patients with moderate stage of IBH – in 33% of cases, in patients with severe stage of IBH – in 57% of cases. Subclinical depression in patients with mild stage of IBH was diagnosed in 12% of cases, in patients with moderate stage of IBH – in 17% of cases, in patients with severe stage of IBH – in 43% of cases. Consequently, a progressive dependence of the level of anxiety and depression on the stage of severity of IBH was revealed. In patients with a Regular Bowel Habit, an "excellent" quality of life was found in 55% of cases. Among patients with IBH, "Excellent" quality of life was found in 10% of cases. Consequently, the probability of an "Excellent" quality of life in patients with RBH was 5 times higher than in patients with IBH. Patients with IBH have an almost 5-fold increased risk of deterioration in the quality of life.

Conclusion

1. Irregular Bowel Habit was detected in 63% of cardiac patients.
2. Irregular Bowel Habit increases the risk of subclinical anxiety gradually from mild to moderate and severe stages of this habit (12%, 33% and 57%, respectively).
3. Irregular Bowel Habit increases the risk of subclinical depression gradually from mild to moderate and severe stages of this habit (12%, 17% and 43%, respectively).
4. A high level of quality of life in patients with a regular (daily) Bowel Habit was 5 times more common than in patients with an Irregular Bowel Habit.

References

1. Guerin A, et al. Risk of developing colorectal cancer and benign colorectal neoplasm in patients with chronic constipation. Alim. Pharm. Ther. 2014 Jul; 40(1):83-92.
2. Kojima M, et al. Bowel movement frequency and risk of colorectal cancer in a large cohort study of Japanese men and women. Br J Cancer 2004 Apr 5; 90(7): 1397–1401.
3. Watanabe T, at al. Constipation, laxative use and risk of colorectal cancer: The Miyagi Cohort Study. Eur J Cancer 2004 Sep;40(14):2109-15. 4. Honkura K., et al. Defecation frequency and cardiovascular disease mortality in Japan. Atherosclerosis. 2016. N246. P. 251–256.
5. Kubota Y., et al. Bowel Movement Frequency, Laxative Use, and Mortality From Coronary Heart Disease and Stroke Among Japanese Men and Women: JACC Study. J Epidemiol. 2016
May 5; 26(5):242-248.
6. Sundbøll J, et al. Constipation and risk of cardiovascular diseases: a Danish population-based matched cohort study. BMJ Open. 2020 Sep 1;10(9): e037080. 7. Shemerovskii K.A. Irregular Bowel Habit Increases Risk of Obesity. United European Gastroenterology Journal. 2015. № A504. P1223. 8. Shemerovskii K.A., et al. Bradyenteria Syndrome and Comorbidity. United European Gastroenterology Journal, Vol. 10. October, 2022. An international forum for clinical practice and
research in gastroenterology. 2022, P.1081. P1003.

Introduction

Irritable bowel syndrome (IBS) is considered a disorder of the altered microbiota-gut-brain axis, where gut dysbiosis and impaired central nervous system processing play important roles. The latter, in the form of depression, anxiety, and gastrointestinal-specific anxiety (GSA), frequently coexist and exacerbate IBS. Probiotics might be a promising therapeutic approach to treat IBS and coexisting depression, anxiety, and GSA.

Aims & Methods

The aim of the trial was to compare the impact of standard care combined with multi-strain probiotics with standard care alone on depression, anxiety, and visceral sensitivity in patients with diarrheal IBS (IBS-D). It was a 12-week randomized trial that included 108 patients with IBS-D that were divided into 2 groups: a control group (n = 51) receiving only standard care (diet, peppermint oil) and an experimental group (n = 57) receiving a combination of standard care (diet, peppermint oil) and the study probiotic (based on Lactobacillus, Streptococcus, Bifidobacterium, and Saccharomyces boulardii strains). Patient Health Questionnaire-9 (PHQ-9) and Beck’s Depression Inventory (BDI) were used to assess depression; the Hospital Anxiety and Depression Scale (HADS) was used to assess anxiety and depression; and the Visceral Sensitivity Index (VSI) was used to assess GSA.

Results

Baseline data were not different between the study groups (p> 0.05). After 12 weeks of treatment, PHQ-9, BDI, and anxiety subscale of HADS were not different between the study groups (p> 0.05), while the central tendency of the depression subscale of HADS in the control group was higher (3 (2-4)) than in the experimental group (3 (2-3)), p = 0.046. VSI was higher in the control group (31±5) compared to the experimental group (29±5.7), p = 0.032, after 12 weeks of trial.

Conclusion

In patients with IBS, additional prescribing of a multi-strain probiotic led to a decrease in depression according to HADS, as well as a reduction in GSA and visceral sensitivity assessed by VSI compared to IBS standard care alone.

Introduction

Gut-brain dysregulation and microbiome dysfunction are central to the pathogenesis of irritable bowel syndrome (IBS). Depressive and anxiety symptoms are highly prevalent and contribute to disease burden but are not commonly addressed in practice. The low FODMAP diet is efficacious for managing gastrointestinal symptoms but may not be appropriate in those with psychological comorbidity due to its complexity. A Mediterranean diet (MD), rich in vegetables, pulses, wholegrains and olive oil, has potential benefit in IBS as it leads to positive shifts in microbiome composition and function, and RCTs have demonstrated antidepressant effects.

Aims & Methods

The TANDIM trial aimed to assess the feasibility of a MD in patients with IBS and psychological comorbidity. Adults aged 18-65 years with Rome IV IBS and mild or moderate anxiety and/or depressive symptoms were recruited to a 6-week RCT. Significant medical or mental health conditions (e.g. inflammatory bowel disease, bipolar disorder) and recent change in IBS or psychotropic treatment were excluded. Patients were randomised to MD advice from a dietitian or advice to continue habitual diet. MD advice was individualised and incorporated advice regarding gradual reintroduction of high fibre or high FODMAP foods in individuals in which these components were restricted. Habitual diet controls undertook identical research activities to MD but were not provided dietary advice. Diet adherence was measured using a Mediterranean diet adherence screener (MEDAS) and 3-day diet records were collected at baseline and follow up. Gastrointestinal symptoms (IBS-SSS), psychological symptoms (HADS) and quality of life (IBS-QOL) data were collected at baseline and follow up. Stool samples were collected for metagenomic sequencing. Data were analysed on an intention-to-treat basis. For continuous variables, analysis of covariance with adjustment for baseline was used; for categorical data, Fisher's exact tests were used. Between group differences in diversity and differential abundance of taxa and potential functions of the microbiome were analysed using linear mixed effects models and FDR correction.

Results

In total, 59 individuals were randomised (29 MD, 30 control) and 48 completed the trial. Seven of 11 withdrawals were due to antibiotic commencement. The MEDAS score was higher, indicating better adherence to MD, at week 6 in MD vs controls (7.5 [95% CI: 6.9, 8.0] vs 5.7 [5.2, 6.3], p<0.001) and there was no difference in total FODMAP intake (p=0.51).There was a lower IBS-SSS at week 6 in MD vs controls (168 [95% CI: 146, 191] vs 260 [95% CI: 238, 282], p<0.001) and a greater proportion of IBS-SSS responders in MD vs controls (≥50-point reduction; 83% vs 37%, p<0.001). There was also a greater proportion of HADS-D responders (52% vs 20%, p=0.015) and IBS-QOL responders (≥14-point reduction 62% vs 23%, p=0.004). Gastrointestinal adverse events were similar between groups (p=0.588). There were no differences between groups in change in microbiome alpha diversity (richness, Shannon Index), beta diversity, relative abundance of taxa, or functional potential.

Conclusion

The MD is a feasible and potentially therapeutic dietary intervention for reducing gut and psychological symptom burden in IBS. The broader health benefits with a MD style eating pattern provide further impetus for studying its effects in IBS. Larger blinded RCTs, in which influence of expectation bias is minimised, are required.

Introduction

Gut microbiota appear to play a role in the pathogenesis of disorders of gut-brain interaction. Established evidence supports the association between gastrointestinal (GI) infections and irritable bowel syndrome (post-infection irritable bowel syndrome, PI-IBS), although the impact of specific taxa has not been clearly assessed yet. Moreover, data associating GI infection and functional dyspepsia (post-infection functional dyspepsia, PI-FD) are emerging.

Aims & Methods

We conducted a systematic review and meta-analysis to determine prevalence of PI-IBS and PI-FD after GI infection and to evaluate if specific microbial taxa differ in their likelihood of precipitating these disorders. We searched PubMed, Scopus, and Web of Science through 17 April 2023. Observational studies recruiting ≥20 adults and reporting prevalence of IBS and/or FD after GI infection with a minimum follow-up duration of 6 months were included. We used a random effects model to calculate pooled prevalence (PP) of IBS and FD as well as odd ratios (OR) with 95% confidence intervals (CIs).

Results

From 8469 papers evaluated, we identified 47 eligible studies (28,071 people) reporting prevalence of PI-IBS and 14 studies of PI-FD (15,253 people), respectively.
Overall, PP of PI-IBS after GI infection was 12.5% (95% CI 11.9%-13.0%, I²= 97,9%) and PP of PI-FD was 12.6% (95% CI 6.3%-20.6%, I²= 94.2%). The PP of PI-IBS was 19.8% for bacteria, 10.7% for viruses, 22.3% for parasites and, notably, 25.7 % for Clostridioides difficile and 22.5% for Campylobacter infections. The PP of PI-FD was 13.6 % for bacteria and 9.6 % for viruses.
Those with a history of GI infection had a significantly higher odds of developing IBS (OR 3.9, 95% CI 2.8-5.4, p<0.0001) or FD (OR 3.03, 95% CI 1.9-4.7, p<0.0001) than controls without.
In subgroup analysis, ORs for developing PI-IBS were 4.8 (95% CI 2.8-8.0, p<0.0001) for bacteria, 3.2 (95% CI 0.9-11,2, p= 0.06) for viruses, and 5.4 (95% CI 4.4-6.7, p < 0.0001) for parasites. Notably, Gram-negative bacteria (Enterobacteriaceae + Campylobacter) were associated with a higher odds (OR 5.5, 95% CI 2.5-11.9, p<0.0001). The OR for developing PI-FD was 3.8 (95% CI 0.98-14.7, p=0.05) for bacteria and 2.0 (95% CI 0.77 to 5.2, p=0.15) for virus, respectively.

Conclusion

In a systematic review and meta-analysis of 61 studies and 43,324 people we found that one-in-eight people who experience a GI infection developed PI-IBS or PI-FD. Bacterial infections, mainly Clostridioides difficile, and parasitic infections were associated with a higher prevalence of PI-IBS or PI-FD. In case-control studies, bacteria, mainly Gram-negatives, and parasites were associated with the highest odds of PI-IBS. Conclusive data on PI-FD are not yet available.

Disclosure

G.I. has received personal fees for acting as speaker for Biocodex, Danone, Sofar, Malesci, Metagenics and Tillotts Pharma, and for acting as consultant and/or advisor for Ferring Therapeutics, Giuliani, Malesci and Tillotts Pharma. A.G. reports personal fees for consultancy from Eisai Srl, 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, SinergieSrl, Board MRGE and Sanofi SpA personal fees for acting as a speaker for Takeda SpA, AbbVie and Sandoz SpA and personal fees for acting on advisory boards for VSL3 and Eisai. G.C. has received personal fees for acting as advisor for Ferring Therapeutics. All other authors have no conflicts of interest to disclose.

Introduction

Irritable bowel syndrome (IBS) is one of the most common disorders of the gut–brain interaction, associated with intestinal microbiota composition, increased gut permeability and psychosocial disturbances^1,2. The pasteurized form of the next generation beneficial microbe, Akkermansia muciniphila, improves gut barrier function and reduces colonic hypersensitivity and anxiety-like behavior in preclinical setting, showing potential in modulation of the gut-brain-axis³.

Aims & Methods

This human study aimed at exploring the effects of pasteurized A. muciniphila on IBS symptoms and psychological function in subjects with moderate IBS.
In a 12-week, randomized, double-blind, placebo-controlled exploratory trial at a single center in Germany, 48 selected individuals diagnosed with IBS (Rome IV criteria), with moderate symptoms based on the IBS Severity Scoring System (IBS-SSS score ≥ 175), were randomized to pasteurized Akkermansia muciniphila at a daily dose of around 30 billion versus placebo in a 2:1 ratio. A main outcome, although not statistically powered, was mean change in IBS-SSS scores from baseline to 12-week endpoint (NCT05348642).

Results

The oral intake of pasteurized Akkermansia muciniphila was very well tolerated. Intent-to-treat analysis revealed clinically meaningful mean improvements from baseline to the 12-week endpoint in the main outcome measure (IBS-SSS) for both pasteurized A. muciniphila (-147.45, SD 94.08) and placebo (-122.25, SD 90.07). Although the pasteurized A. muciniphila group reported numerically higher improvement than the placebo group, the difference between the groups was not statistically significant. The IBS-SSS parameter had decreased already by 44% and 37% of the initial values in the verum and placebo arms respectively at the 2-week timepoint, reflecting a relatively quick effect. At the level of the psychological scores, the Hospital Anxiety and Depression Scores were in the normal range at baseline, improved with 10 and 5% in the verum group, and worsened by 11 and 35% in the placebo arm from the initial anxiety and depression parameters respectively.

Conclusion

Pasteurized Akkermansia muciniphila showed clinically meaningful but not statistically significant improvement over placebo in IBS symptoms in subjects with moderate IBS. The psychological scores improved mildly in the verum group while worsening in the placebo arm. These results support the potential of pasteurized Akkermansia muciniphila to modulate the gut–brain interaction in IBS subjects.

References

1 Barbara G, Grover M, Bercik P, Corsetti M, Ghoshal UC, Ohman L, Rajilić-Stojanović M. Rome foundation working team report on post-infection irritable bowel syndrome. Gastroenterology 2019;156:46–58,
2 Huang HL, Chen HT, Luo QL, Xu HM, He J, Li YQ, Zhou YL, Yao F, Nie YQ, Zhou YJ. Relief of irritable bowel syndrome by fecal microbiota transplantation is associated with changes in diversity and composition of the gut microbiota. J Dig Dis. 2019;20:401-408
3 Paper with the scientific data submitted to and currently in review by peer reviewed journal.

Disclosure

The trial is sponsored by The Akkermansia Company SA that is developing and commercializing pasteurized Akkermansia muciniphila.

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