[Long-term probiotic administration for irritable bowel syndrome: a legal need].

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional diseases of the gastrointestinal tract. Violations in the intestinal microbiocenosis play a significant role in the pathogenesis of this suffering. The probiotic strain Bifidobacterium longum 35624® has a strong evidence base for use in the management of patients with IBS. The duration of probiotic therapy and the need for repeated courses of probiotics require further study, which determined the need for this observational study. AIM: To compare the results of prolonged (12 weeks) and usual duration of courses of probiotic Bifidobacterium longum 35624® in patients with IBS. MATERIALS AND METHODS: 42 patients with a verified diagnosis of IBS of moderate and severe severity who met the inclusion criteria were recruited into the study. Patients were prescribed probiotic Bifidobacterium longum 35624® at a dose of 1 capsule (1×109 CFU), 1 time per day for 12 weeks. The course of the disease was assessed using the visual analogue scale, visceral sensitivity index (VSI), IBS symptom severity scale (IBS-SSS), quality of life indicators were assessed using the IBS-QoL questionnaire scales. Evaluation of indicators was carried out at the inclusion visit, on days 14, 28, 56, 84 of probiotic intake and on day 112 (28 days after the last dose of Bifidobacterium longum 35624®). RESULTS: The results obtained confirmed the ability of the probiotic Bifidobacterium longum 35624® to positively influence the course of IBS. The addition of the main therapy with a probiotic made it possible to achieve a significant decrease in the severity of abdominal pain, bloating, and stool disorders. The severity of IBS significantly decreased according to the results of IBS-SSS. Reliable positive dynamics of indicators on the scales IBS-QoL, VSI is shown. The most pronounced changes were observed by the end of the third month of taking Bifidobacterium longum 35624®. Thus, according to the IBS-SSS indicators, only by the end of the third month of observation, some patients achieved remission of the disease. All described changes were persistent and persisted one month after the end of the probiotic intake. CONCLUSION: The addition of a prolonged course of the probiotic Bifidobacterium longum 35624® to the basic therapy in patients with IBS allows a more pronounced and lasting effect to be achieved. A "post-probiotic" effect was shown - a decrease in VSI after the end of the intake of the probiotic strain. Given the chronic relapsing course of IBS, the use of repeated probiotic courses was proposed to prevent exacerbation of the disease.

Fecal microbiota transplantation in patients with irritable bowel syndrome: an overview of current studies.

As dysbiosis is a key factor associated with irritable bowel syndrome (IBS), modulation of the intestinal microbiota could improve IBS symptoms and quality of life. Fecal microbiota transplantation (FMT) could be one efficient way to restore bacterial composition in IBS patients. This review comprises 12 clinical trials published from 2017 to 2021. Inclusion criteria were the assessment of IBS symptoms using the IBS symptom severity score, quality of life measured by the lBS quality of life scale, and gut microbiota analysis. Improved symptoms were reported in all 12 studies, paralleling with an increased quality of life after FMT, but also partly after placebo treatment. The use of oral capsules showed that the placebo treatment can have similar or even stronger positive effects on IBS patients than FMT. Gastroscopic FMT appears to link modulation of the gut microbiome to significant symptom reduction in patients. The patient's microbiota profile shifted toward their respective donors. Symptom worsening or decreased quality of life after FMT was not reported. The results show that FMT could be a therapeutic approach in IBS patients. Further research is needed to investigate whether FMT has a more beneficial effect on IBS patient than placebo treatment with the patient's own stool, placebo capsules, or bowel cleansing. Moreover, optimal donor selection, frequency, dosage, and route of delivery still need to be defined.

The efficacy of vitamin D supplementation for irritable bowel syndrome: narrow scope and GRADE miss-interpretation.

We read the article by Haung et al. that pooled the effects of vitamin D on irritable bowel syndrome symptoms and associated quality of life. However, the current review suffers from some methodological errors: inadequate search strategy; the grading of recommendations assessment, development, and evaluation (GRADE) miss-assessment; and miss-interpretation. Accordingly, addressing the emphasized limitations will lead to more robust findings and conclusions.

Factors associated with lower disease-specific and generic health-related quality of life in Rome IV irritable bowel syndrome.

BACKGROUND: Little is known about associations with reduced quality of life in irritable bowel syndrome (IBS) or impact of IBS on quality of life compared with other chronic conditions. METHODS: We collected demographic, gastrointestinal and psychological symptoms, healthcare usage, direct healthcare costs, impact on work and activities of daily living data from 752 individuals with Rome IV-defined IBS. We used the irritable bowel syndrome quality of life (IBS-QOL) and the EQ-5D-5L questionnaires to examine characteristics associated with lower quality of life. RESULTS: The mean IBS-QOL among all 752 individuals with Rome IV IBS was 48.4 (SD 22.3) and the mean EQ-5D score was 0.570 (SD 0.283), the latter being comparable to people with stroke, leg ulcers or chronic obstructive pulmonary disease. Lower levels of both disease-specific and generic quality of life were associated with severe IBS symptom scores, abnormal anxiety or depression scores, and higher somatoform symptom-reporting and gastrointestinal symptom-specific anxiety scores (p < 0.001 for all analyses). Those with lower quality of life had significantly higher healthcare usage and direct healthcare costs and more impairment in work and activities of daily living (p < 0.01 for all analyses). Avoidance of alcohol, lower educational level, abnormal anxiety, depression or somatoform symptom-reporting scores, and impairment in social leisure activities, home management or maintaining close relationships were all independently associated with lower quality of life. CONCLUSION: IBS has a substantial impact on the quality of life of those affected, and worse than observed in some severe chronic organic conditions.

The estimation of a preference-based single index for the IBS-QoL by mapping to the EQ-5D-5L in patients with irritable bowel syndrome.

PURPOSE: The Irritable Bowel Syndrome Quality of Life (IBS-QoL) questionnaire is a commonly used and validated IBS-specific QoL instrument. However, this questionnaire is in contrast to the EQ-5D-5L, not preference-based and as such does not allow calculation of QALYs. The objective of this study was to describe the convergent- and known-group validity of both questionnaires and to develop a mapping algorithm from EQ-5D-5L which enable IBS-QoL scores to be transformed into utility scores for use in economic evaluations. METHODS: We used data from two multicenter randomized clinical trials, which represented the estimation and external validation dataset. The convergent validity was investigated by examining correlations between the EQ-5D-5L and IBS-QoL and the known-group validity by calculating effect sizes. Ordinary least squares (OLS), censored least absolute deviations (CLAD), and mixture models were used in this mapping approach. RESULTS: 283 IBS patients were included (n = 189 vs. n = 84). Mean IBS-QoL score was 71.13 (SD 15.66) and mean EQ-5D-5L utility score was 0.73 (SD 0.19). The overall sensitivity of the IBS-QoL and EQ-5D-5L to discriminate between patient and disease characteristics was similar. CLAD model 4, containing the total IBS-QoL score and squared IBS-SSS (IBS severity scoring system), was chosen as the most appropriate model to transform IBS-QoL scores into EQ-5D-5L utility scores. CONCLUSION: This study reports the development of an algorithm where the condition-specific questionnaire IBS-QoL can be used to calculate utility values for use in economic evaluations. Including a clinical measure, IBS-SSS, in the model improved the performance of the algorithm.

The impact of treatment with eluxadoline on health-related quality of life among adult patients with irritable bowel syndrome with diarrhea.

PURPOSE: Irritable bowel syndrome with diarrhea (IBS-D) significantly impacts health-related quality of life (HRQOL). This post hoc analysis of two phase III trials evaluated the effects of eluxadoline treatment on disease-specific HRQOL among patients with IBS-D. METHODS: Adult patients meeting Rome III criteria for IBS-D were randomized to oral eluxadoline (75 mg or 100 mg) or placebo twice daily in two phase III clinical trials for 52 weeks (IBS-3001) and 26 weeks (IBS-3002). The Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire assessed disease-specific HRQOL throughout the study. Changes from baseline to Week 26 in IBS-QOL total and subscale scores were analyzed using an analysis of covariance model. Percentages of IBS-QOL responders with ≥ 14- and 20-point changes were evaluated for IBS-QOL total and subscale scores. A longitudinal mixed-effects model was fitted to evaluate mean IBS-QOL total scores. A cumulative distribution function for change from baseline to Week 26 in IBS-QOL total score was plotted. RESULTS: Mean changes from baseline to Week 26 for the IBS-QOL total and all subscale scores were significantly higher for patients treated with eluxadoline (both doses) compared to placebo. A significantly greater proportion of eluxadoline-treated patients were responders compared to placebo. Mean and mixed-effects model estimated mean IBS-QOL total scores were consistently higher for eluxadoline versus placebo over 52 weeks. CONCLUSIONS: Compared to placebo, twice-daily eluxadoline treatment significantly improved HRQOL among patients with IBS-D in two phase III trials.

A double blind, placebo-controlled, randomized clinical trial that breast milk derived-Lactobacillus gasseri BNR17 mitigated diarrhea-dominant irritable bowel syndrome.

The exact pathogenesis of diarrhea-dominant irritable bowel syndrome (IBS) is not known, but the abnormal microbiota of the gastrointestinal tract is considered to be one of the important contributing factors as in other gastrointestinal diseases such as inflammatory bowel disease, antibiotic-associated diarrhea, and colorectal cancer as well as systemic diseases. Though diverse trials of probiotics had been continued in the treatment of diarrhea-IBS, only a few proved by randomized clinical trial. To prove the efficacy of Lactobacillus gasseri BNR17 isolated from breast milk in patients with diarrhea-IBS, prospective, randomized, placebo controlled clinical trial was done including health related-quality of life analysis, colon transit time, and the changes of fecal microbiota. BNR17 significantly improved the symptoms of diarrhea compared to control group. Health related-QOL analysis showed significant improvement of abdominal pain, distension, disturbed daily life, and mean defecation frequency with BNR17. On comparative CTT before and after BNR17, 6 out of 24 subjects showed significant correction of rapid colon transit pattern, while only 2 out of 24 in placebo (p<0.01). Upon fecal microbiota analysis, BNR17 significantly increased B. fecalis, E. rectale, C. aerofaciens, F. prausnitzil and B. steroris. Conclusively, Lactobacillus gasseri BNR17 can be a potential probiotics to ameliorate diarrhea-IBS.

Medical comorbidity and distress in patients with irritable bowel syndrome: The moderating role of age.

OBJECTIVES: Irritable bowel syndrome (IBS) affects people across the age spectrum and is highly comorbid with other medical conditions. The aim of this study was to determine the moderating effect of age on the relationship between medical comorbidity and health outcomes in IBS patients. METHODS: Patients (n=384) across the age spectrum (18 to 70) completed questionnaires regarding medical comorbidities, anxiety, depression, IBS symptom severity, and IBS quality of life (QOL). RESULTS: The mean age was 41 (SD=15). Age interacted with medical comorbidities to predict anxiety, F(7,354)=5.82, p=0.009, R(2)=0.10. Results revealed significant main effects for education, ß=-0.16, p<0.05, age, ß=-0.15, p<0.05, medical comorbidities, ß=0.25, p<0.05, and a significant interaction, ß=-0.15, p<0.01. Anxiety was greater among patients with many comorbidities, with this effect being more pronounced for younger adults. Depression, also predicted by the interaction between age and comorbidities, showed the same pattern as anxiety. There was no significant interaction between age and medical comorbidities in predicting IBS symptom severity or IBS QOL. CONCLUSION: Distress among IBS patients with medical comorbidities varies with age, with higher levels of anxiety and depression among younger adults than their older counterparts. Medical comorbidity may have a more selective impact on psychological distress as compared to IBS symptom severity and quality of life for younger adults with IBS. Distress may increase IBS burden for these patients and complicate its medical management.

Item-level assessment of the irritable bowel syndrome quality of life questionnaire in patients with diarrheal irritable bowel syndrome.

BACKGROUND: In previous studies, the Irritable Bowel Syndrome Quality of Life (IBS-QOL) instrument has been determined to have good measurement properties for general irritable bowel syndrome (IBS) and the diarrheal IBS (IBS-d) subtype in clinical trials. OBJECTIVE: This article aims to extend the true-score analyses that have been previously conducted to evaluate the IBS-QOL in IBS-d patients. METHODS: Item response theory analysis was conducted by fitting models to responses from 753 patients with severe IBS-d from a recent clinical trial. Three item response theory models, the constrained graded response model (CGRM), the unconstrained GRM (UGRM), and the testlet response model (TRM), were fit to the 34 items of the IBS-QOL questionnaire. Subsequently, differential item functioning (DIF) for patient sex was assessed by fitting nested models by applying likelihood ratio tests. Model latent trait estimates were then compared with the IBS-QOL score and the IBS Symptom Severity Score. RESULTS: Model fits improved with complexity, with the TRM model fitting best compared with the CGRM and UGRM. The DIF evaluation for patient sex flagged 17 items for the CGRM and 9 items for the UGRM; however, these items were not found to have much effect on the overall estimation of the latent trait. Differential testlet functioning was not indicated, and no items exhibited potential DIF under the TRM because likelihood ratio tests were not statistically significant. Comparison of latent trait estimates to the IBS Symptom Severity Score and IBS-QOL questionnaire revealed high Spearman correlations (0.47 and ≥0.99, respectively). CONCLUSION: Previous true-score approach results were supported by the IBS-QOL item-level analysis. Further, the IBS-QOL total score was found to be a valid measure of perceived quality of life for IBS-d patients when compared with more sophisticated model-based estimates of perceived quality of life. ClinicalTrials.gov identifier: NCT01130272.

Effect of linaclotide in irritable bowel syndrome with constipation (IBS-C): a systematic review and meta-analysis.

BACKGROUND: Treatment options for constipation-predominant irritable bowel syndrome (IBS-C) are limited. While linaclotide improved IBS-C symptoms in randomized controlled trials (RCTs), results vary among studies and the magnitude of benefit is unclear. METHODS: Two investigators independently extracted data on study participants, methods and outcomes (i.e., symptoms, quality of life, and adverse events) from eligible articles i.e., RCTs comparing linaclotide with placebo in adult patients with IBS-C with a follow-up of 12 weeks or longer. The grading of recommendations assessment, development and evaluation (GRADE) methodology was used to rate the quality of evidence. KEY RESULTS: Of 182 identified citations, three RCTs enrolling 1773 patients met the inclusion criteria. Compared with placebo, fewer patients on linaclotide failed to achieve responses i.e., FDA endpoint (1604 patients, risk ratio [RR] = 0.80; 95%CI 0.76-0.85), adequate IBS symptom relief (1773 patients, RR = 0.73; 95%CI 0.65-0.82), and clinically meaningful improvement in IBS-QOL (1659 patients, RR = 0.78; 95%CI 0.72-0.86). The incidence of diarrhea leading to discontinuation of treatment was higher for linaclotide (1773 patients, RR = 14.75; 95%CI 4.04-53.81). The quality of evidence was rated as moderate for FDA endpoint and adequate relief response, high for diarrhea, and low for IBS-QOL. Generalizability may be limited by the study population (i.e., predominantly white female patients), lack of data regarding prior therapy, and availability of few RCTs. The number of patients is insufficient to identify rare adverse events. CONCLUSIONS & INFERENCES: Linaclotide is moderately effective in improving symptoms of IBS-C with diarrhea being the major side effect. Further studies are needed to evaluate the long-term efficacy and safety of linaclotide for IBS-C.

Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study.

BACKGROUND & AIMS: Simultaneous agonism of the µ-opioid receptor and antagonism of the δ-opioid receptor can reduce abdominal pain and diarrhea in patients with irritable bowel syndrome with diarrhea (IBS-D) without constipating side effects. We evaluated the efficacy and safety of a minimally absorbed, µ-opioid receptor agonist and δ-opioid receptor antagonist (eluxadoline) in a phase 2 study in patients with IBS-D. METHODS: We randomly assigned 807 patients to groups that received oral placebo twice daily or 5, 25, 100, or 200 mg oral eluxadoline for 12 weeks. The primary end point was clinical response at week 4, defined by a mean reduction in daily pain score from baseline of ≥ 30%, and of at least 2 points on 0-10 scale, as well as a stool consistency score of 3 or 4 on the Bristol Stool Scale (1-7) for at least 66% of daily diary entries during that week. RESULTS: Significantly more patients receiving 25 mg (12.0%) or 200 mg (13.8%) eluxadoline met the primary end point of clinical response than patients given placebo (5.7%; P < .05). Patients receiving eluxadoline at 100 mg and 200 mg also had greater improvements in bowel movement frequency and urgency, global symptoms, quality of life, and adequate relief assessments (P < .05). Additionally, patients receiving 100 mg (28.0%) or 200 mg (28.5%) eluxadoline were significantly more likely than those receiving placebo (13.8%; P < .005) to meet the US Food and Drug Administration response end point during the full 12 weeks of the study. Eluxadoline was well tolerated with a low incidence of constipation. CONCLUSIONS: In a phase 2 study of the mixed µ-opioid receptor agonist/δ-opioid receptor antagonist eluxadoline vs placebo in patients with IBS-D, patients given eluxadoline were significantly more likely to be clinical responders, based on a composite of improvement in abdominal pain and stool consistency. Further study of eluxadoline is warranted to assess its potential as a treatment for IBS-D.