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Fecal Microbiota Transplantation Is Highly Effective in Real-World Practice: Initial Results From the FMT National Registry.
Kelly, CR, Yen, EF, Grinspan, AM, Kahn, SA, Atreja, A, Lewis, JD, Moore, TA, Rubin, DT, Kim, AM, Serra, S, et al
Gastroenterology. 2021;(1):183-192.e3
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Abstract
BACKGROUND & AIMS Fecal microbiota transplantation (FMT) is used commonly for treatment of Clostridioides difficile infections (CDIs), although prospective safety data are limited and real-world FMT practice and outcomes are not well described. The FMT National Registry was designed to assess FMT methods and both safety and effectiveness outcomes from North American FMT providers. METHODS Patients undergoing FMT in clinical practices across North America were eligible. Participating investigators enter de-identified data into an online platform, including FMT protocol, baseline patient characteristics, CDI cure and recurrence, and short and long-term safety outcomes. RESULTS Of the first 259 participants enrolled at 20 sites, 222 had completed short-term follow-up at 1 month and 123 had follow-up to 6 months; 171 (66%) were female. All FMTs were done for CDI and 249 (96%) used an unknown donor (eg, stool bank). One-month cure occurred in 200 patients (90%); of these, 197 (98%) received only 1 FMT. Among 112 patients with initial cure who were followed to 6 months, 4 (4%) had CDI recurrence. Severe symptoms reported within 1-month of FMT included diarrhea (n = 5 [2%]) and abdominal pain (n = 4 [2%]); 3 patients (1%) had hospitalizations possibly related to FMT. At 6 months, new diagnoses of irritable bowel syndrome were made in 2 patients (1%) and inflammatory bowel disease in 2 patients (1%). CONCLUSIONS This prospective real-world study demonstrated high effectiveness of FMT for CDI with a good safety profile. Assessment of new conditions at long-term follow-up is planned as this registry grows and will be important for determining the full safety profile of FMT.
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Patient-Specific Stress-Abdominal Pain Interaction in Irritable Bowel Syndrome: An Exploratory Experience Sampling Method Study.
Vork, L, Keszthelyi, D, van Kuijk, SMJ, Quetglas, EG, Törnblom, H, Simrén, M, Aziz, Q, Corsetti, M, Tack, J, Mujagic, Z, et al
Clinical and translational gastroenterology. 2020;(7):e00209
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INTRODUCTION Gastrointestinal symptoms in irritable bowel syndrome (IBS) have been correlated with psychological factors using retrospective symptom assessment. However, real-time symptom assessment might reveal the interplay between abdominal and affective symptoms more reliably in a longitudinal perspective. The aim was to evaluate the association between stress and abdominal pain, using the Experience Sampling Method (ESM) as a real-time, repeated measurement method. METHODS Thirty-seven patients with IBS (26 women; mean age 36.7 years) and 36 healthy controls (HC; 24 women; mean age 31.1 years) completed an electronic ESM during 7 consecutive days. Abdominal pain and stress were scored on an 11-point Numeric Rating Scale at a maximum of 10 random moments each day. RESULTS Abdominal pain scores were 2.21 points higher in patients with IBS compared with those in HC (P < 0.001), whereas stress levels did not differ significantly (B: 0.250, P = 0.406). In IBS, a 1-point increase in stress was associated with, on average, 0.10 points increase in abdominal pain (P = 0.017). In HC, this was only 0.02 (P = 0.002). Stress levels at t = -1 were not a significant predictor for abdominal pain at t = 0 in both groups, and vice versa. DISCUSSION Our results demonstrate a positive association between real-time stress and abdominal pain scores and indicate a difference in response to stress and not a difference in experienced stress per se. Furthermore, an in-the-moment rather than a longitudinal association is suggested. This study underlines the importance of considering the individual flow of daily life and supports the use of real-time measurement when interpreting potential influencers of abdominal symptoms in IBS.
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Volatile Organic Compounds in Feces Associate With Response to Dietary Intervention in Patients With Irritable Bowel Syndrome.
Rossi, M, Aggio, R, Staudacher, HM, Lomer, MC, Lindsay, JO, Irving, P, Probert, C, Whelan, K
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2018;(3):385-391.e1
Abstract
BACKGROUND & AIMS Dietary interventions are effective in management of patients with irritable bowel syndrome (IBS), although responses vary. We investigated whether fecal levels of volatile organic compounds (VOCs) associate with response to dietary interventions in patients with IBS. METHODS Adults who fulfilled the Rome III criteria for IBS were recruited to a 2x2 factorial randomized controlled trial. Patients were randomly assigned to a group counselled to follow a diet low in fructans, galacto-oligosaccharides, lactose, fructose, and polyols (low-FODMAP diet, n = 46) or a group that received placebo dietary advice (sham diet, n = 47) for 4 weeks. Patients from each group were also given either a multi-strain probiotic or placebo supplement. Response was defined as a reduction of 50 points or more on the validated IBS symptom scoring system. Fecal samples were collected from participants at baseline and end of the 4-week study period; VOCs were analyzed by a gas-chromatography sensor device. VOC profiles were determined using a pipeline involving wavelet transformation followed by feature selection based on random forest. A partial least squares classifier was constructed to classify VOC profiles by response and accuracies were determined using 10-fold cross-validation. RESULTS Data from 93 patients who completed the study (63 female) were used in the final analysis. More patients responded to the low-FODMAP diet (37/46, 80%) than the sham diet (21/47, 45%) (P < .001), but there was no difference in response between patients given the probiotic (31/49, 63%) vs the placebo (27/44, 61%) (P = .850), with no interaction between the diet and supplement interventions. At baseline, VOC profiles contained 15 features that classified response to the low-FODMAP diet with a mean accuracy of 97% (95% CI, 96%-99%) and 10 features that classified response to probiotic with a mean accuracy of 89% (95% CI, 86%-92%). End of treatment models achieved similar predictive powers and accuracies. CONCLUSION Fecal VOC profiling is a low cost, non-invasive tool that might be used to predict responses of patients with IBS to low-FODMAP diet and probiotics and identify their mechanisms of action. ISRCTN registry no: 02275221.
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Assessment of the effectiveness and safety of ethosuximide in the treatment of abdominal pain related to irritable bowel syndrome - IBSET: protocol of a randomised, parallel, controlled, double-blind and multicentre trial.
Kerckhove, N, Scanzi, J, Pereira, B, Ardid, D, Dapoigny, M
BMJ open. 2017;(7):e015380
Abstract
INTRODUCTION Irritable bowel syndrome (IBS) is characterised by the association of abdominal chronic pain with bowel habit disorders in the absence of identifiable organic disease. This is the first reason for consultation in gastroenterology, with an estimated prevalence of 10%-15% in industrialised countries. Although this is a benign gastrointestinal disease, its chronicity profoundly impacts the patient's quality of life and causes considerable health spending. Actual medical treatments are poorly efficient on IBS-related abdominal pain, making it a major public health concern. The mechanisms causing IBS symptoms are unknown. Recent studies have shown the involvement of T-type channel in abdominal pain. We aim to evaluate the therapeutic potential of ethosuximide, a T-type channel blocker, on the abdominal pain of patients presenting an IBS. METHODS AND ANALYSIS The IBSET trial is a randomised, controlled, parallel, double-blind and multicentre study. It is the first clinical trial evaluating the efficacy and safety of ethosuximide on abdominal pain related to IBS. Adults with IBS that report significant abdominal pain (≥4/10) at least for 3 months will be included. 290 patients will be randomly assigned to receive either ethosuximide or placebo over 12 weeks after 1 week of run-in period. The primary endpoint is the rate of responders (pain reduction ≥30% and Subject Global Assessment of Relief score ≥4). The intensity of abdominal pain will be assessed by an 11-point Numerical Rating Scale before and after 12 weeks of treatment and the score of the Subject Global Assessment of Relief scale at the end of treatment. The secondary endpoints are the safety of ethosuximide, the intensity and features of IBS and quality of life. ETHICS AND DISSEMINATION The study was approved by an independent medical ethics committee (CPP Sud-Est VI, Clermont-Ferrand, France). The results will be published in a peer-review journal and presented at international congresses. TRIAL REGISTRATION NUMBER NCT02973542; Pre-results.
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Evaluation of Benefit and Tolerability of IQP-CL-101 (Xanthofen) in the Symptomatic Improvement of Irritable Bowel Syndrome: A Double-Blinded, Randomised, Placebo-Controlled Clinical Trial.
Alt, F, Chong, PW, Teng, E, Uebelhack, R
Phytotherapy research : PTR. 2017;(7):1056-1062
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Irritable bowel syndrome (IBS) is a functional bowel disorder of unknown aetiology. There is currently no known cure, and pharmacological interventions are usually targeting symptomatic relief, where natural and herbal remedies also play a role. This study aimed to evaluate the benefit and tolerability of IQP-CL-101 in symptomatic IBS relief. A double-blinded, randomised, placebo-controlled trial was conducted over 8 weeks. A total of 99 subjects fulfilling ROME-III criteria for IBS were randomised into two groups, given either two IQP-CL-101 softgels or matching placebo twice daily before main meals. The primary endpoint was the difference in change of IBS Symptom Severity Score (IBS-SSS) after an 8-week intake of IQP-CL-101 compared to placebo. After 8 weeks, subjects on IQP-CL-101 showed a significant reduction in IBS-SSS (113.0 ± 64.9-point reduction) compared to subjects on placebo (38.7 ± 64.5-point reduction) (p < 0.001). A significant improvement could be seen as early as 4 weeks. No serious adverse events were reported throughout. IQP-CL-101 can be considered beneficial in the improvement of IBS symptom severity, regardless of IBS type, and therefore able to improve quality of life in patients suffering from abdominal pain and discomfort. © 2017 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.
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Randomised controlled trial of mesalazine in IBS.
Barbara, G, Cremon, C, Annese, V, Basilisco, G, Bazzoli, F, Bellini, M, Benedetti, A, Benini, L, Bossa, F, Buldrini, P, et al
Gut. 2016;(1):82-90
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OBJECTIVE Low-grade intestinal inflammation plays a role in the pathophysiology of IBS. In this trial, we aimed at evaluating the efficacy and safety of mesalazine in patients with IBS. DESIGN We conducted a phase 3, multicentre, tertiary setting, randomised, double-blind, placebo-controlled trial in patients with Rome III confirmed IBS. Patients were randomly assigned to either mesalazine, 800 mg, or placebo, three times daily for 12 weeks, and were followed for additional 12 weeks. The primary efficacy endpoint was satisfactory relief of abdominal pain/discomfort for at least half of the weeks of the treatment period. The key secondary endpoint was satisfactory relief of overall IBS symptoms. Supportive analyses were also performed classifying as responders patients with a percentage of affirmative answers of at least 75% or >75% of time. RESULTS A total of 185 patients with IBS were enrolled from 21 centres. For the primary endpoint, the responder patients were 68.6% in the mesalazine group versus 67.4% in the placebo group (p=0.870; 95% CI -12.8 to 15.1). In explorative analyses, with the 75% rule or >75% rule, the percentage of responders was greater in the mesalazine group with a difference over placebo of 11.6% (p=0.115; 95% CI -2.7% to 26.0%) and 5.9% (p=0.404; 95% CI -7.8% to 19.4%), respectively, although these differences were not significant. For the key secondary endpoint, overall symptoms improved in the mesalazine group and reached a significant difference of 15.1% versus placebo (p=0.032; 95% CI 1.5% to 28.7%) with the >75% rule. CONCLUSIONS Mesalazine treatment was not superior than placebo on the study primary endpoint. However, a subgroup of patients with IBS showed a sustained therapy response and benefits from a mesalazine therapy. TRIAL REGISTRATION NUMBER ClincialTrials.gov number, NCT00626288.
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Irritable bowel syndrome symptom severity improves equally with probiotic and placebo.
Lyra, A, Hillilä, M, Huttunen, T, Männikkö, S, Taalikka, M, Tennilä, J, Tarpila, A, Lahtinen, S, Ouwehand, AC, Veijola, L
World journal of gastroenterology. 2016;(48):10631-10642
Abstract
AIM: To determine the effects of Lactobacillus acidophilus NCFM on irritable bowel syndrome (IBS) symptoms and quality of life (QoL). METHODS In this randomized triple-blind trial, adult IBS volunteers who were recruited according to Rome III criteria received 109 or 1010 colony-forming units of NCFM or placebo daily for 12 wk. IBS Symptom Severity Score (IBS-SSS), which constituted the primary outcome, and secondary outcomes, including individual IBS symptoms, IBS-related QoL questionnaire, anxiety and depression, defecation frequency, and stool consistency, were assessed at baseline at the end of the 8-wk run-in period, after 4 and 12 wk of intervention, and after a 4-wk washout. RESULTS A total of 340 of 391 randomized volunteers completed the trial. IBS-SSS improved over 12 wk of treatment in all treatment groups, decreasing by a mean ± SD of 44.0 ± 80.2, 50.8 ± 82.4, and 48.3 ± 72.2 in the placebo, active low-dose, and active high-dose groups, respectively. Similarly, secondary outcomes did not differ between treatment groups. However, in a post hoc analysis of volunteers with moderate to severe abdominal pain at baseline (VAS > 35/100), the treatment significantly reduced the sensation of abdominal pain. Pain scores fell by 20.8 ± 22.8, 29.4 ± 17.9, and 31.2 ± 21.9 in the placebo, active low-dose, and active high-dose groups, respectively (P value for placebo vs combined active doses = 0.0460). CONCLUSION NCFM alleviates moderate to severe abdominal pain, consistent with earlier observations of this strain mitigating visceral pain through increased analgesic receptor expression.
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Bacillus coagulans MTCC 5856 supplementation in the management of diarrhea predominant Irritable Bowel Syndrome: a double blind randomized placebo controlled pilot clinical study.
Majeed, M, Nagabhushanam, K, Natarajan, S, Sivakumar, A, Ali, F, Pande, A, Majeed, S, Karri, SK
Nutrition journal. 2016;:21
Abstract
BACKGROUND Bacillus coagulans MTCC 5856 has been marketed as a dietary ingredient, but its efficacy in diarrhea predominant irritable bowel syndrome (IBS) condition has not been clinically elucidated till date. Thus, a double blind placebo controlled multi-centered trial was planned to evaluate the safety and efficacy of B. coagulans MTCC 5856 in diarrhea predominant IBS patients. METHODS Thirty six newly diagnosed diarrhea predominant IBS patients were enrolled in three clinical centres. Along with standard care of treatment, 18 patients in group one received placebo while in group two 18 patients received B. coagulans MTCC 5856 tablet containing 2 × 10(9) cfu/day as active for 90 days. Clinical symptoms of IBS were considered as primary end point measures and were evaluated through questionnaires. The visual analog scale (VAS) was used for abdominal pain. Physician's global assessment and IBS quality of life were considered as secondary efficacy measures and were monitored through questionnaires. RESULTS Laboratory parameters, anthropometric and vital signs were within the normal clinical range during the 90 days of supplementation in placebo and B. coagulans MTCC 5856 group. There was a significant decrease in the clinical symptoms like bloating, vomiting, diarrhea, abdominal pain and stool frequency in a patient group receiving B. coagulans MTCC 5856 when compared to placebo group (p < 0.01). Similarly, disease severity also decreased and the quality of life increased in the patient group receiving B. coagulans MTCC 5856 when compared to placebo group. CONCLUSIONS The study concluded that the B. coagulans MTCC 5856 at a dose of 2 × 10(9) cfu/day along with standard care of treatment was found to be safe and effective in diarrhea predominant IBS patients for 90 days of supplementation. Hence, B. coagulans MTCC 5856 could be a potential agent in the management of diarrhea predominant IBS patients.
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Exploring the genetics of irritable bowel syndrome: a GWA study in the general population and replication in multinational case-control cohorts.
Ek, WE, Reznichenko, A, Ripke, S, Niesler, B, Zucchelli, M, Rivera, NV, Schmidt, PT, Pedersen, NL, Magnusson, P, Talley, NJ, et al
Gut. 2015;(11):1774-82
Abstract
OBJECTIVE IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies. DESIGN We conducted a GWA study (GWAS) of IBS in a general population sample of 11,326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls. RESULTS One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein), showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31×10(-6) in a meta-analysis of all datasets. Several SNPs in this region are associated with cis effects on KDELR2 expression, and a trend for increased mucosal KDLER2 mRNA expression was observed in IBS cases compared with controls. CONCLUSIONS Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations.
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Efficacy and safety profile of LCR35 complete freeze-dried culture in irritable bowel syndrome: a randomized, double-blind study.
Dapoigny, M, Piche, T, Ducrotte, P, Lunaud, B, Cardot, JM, Bernalier-Donadille, A
World journal of gastroenterology. 2012;(17):2067-75
Abstract
AIM: To assess the effects and safety of Lactobacillus casei rhamnosus LCR35 complete freeze-dried culture (LCR35) in patients suffering from irritable bowel syndrome (IBS). METHODS A randomized, double-blind pilot study was performed in 50 patients complaining of IBS symptoms complying with Rome III criteria. Patients were allocated to receive either LCR35 (n = 25) at a minimum daily dose of 6 × 10(8) colony forming units or placebo (n = 25) for 4 wk. At inclusion, after treatment and 2 wk later, patients completed the IBS severity scale. Change from baseline in the IBS severity score at the end of treatment was the primary efficacy criterion. Changes were compared between groups in the whole population and in IBS subtypes (IBS with predominance of constipation, IBS with predominance of diarrhoea, mixed IBS, unsubtyped IBS). The presence of lactobacillus casei rhamnosus in stools was investigated at inclusion and at the end of treatment. The gastrointestinal quality of life questionnaire and the hospital anxiety and depression (HAD) scale were also completed. RESULTS Both groups were balanced for baseline characteristics. In 85% of patients, stool analyses showed that lactobacillus casei rhamnosus able to survive in the digestive tract. In the whole population, improvements in the IBS severity score did not differ significantly between treatments with a 25% decrease after 4-wk treatment, and a 15% decrease from baseline 2 wk later in both groups. In IBS subgroups, statistical analysis could not be performed due to small sample size, but a clinical response in favour of LCR35 was observed in IBS patients with predominance of diarrhoea: no change in the symptom severity score was seen with the placebo after 4 wk treatment, whereas a clinically relevant decrease occurred with LCR35 (-37% vs -3%). Furthermore, in spite of an increase in symptom intensity, the IBS severity score was maintained below the baseline value 2 wk later with LCR35 (-19% from baseline), whilst a slight 5% increase from baseline was observed with placebo. In the IBS subgroup with predominance of diarrhoea only, a clinically relevant decrease in abdominal pain severity score (-36%) was observed with LCR35, whereas no change occurred with placebo. In mixed IBS patients, the 20% and 30% decreases in the IBS severity score observed after treatment with LCR35 and placebo, respectively, were maintained 2 wk later in both groups. A clinical response slightly in favour of placebo was observed at the end of the treatment period in IBS patients with predominance of constipation (-41% vs -20%) and unsubtyped IBS patients (-47% vs -17%), with the same value maintained 2 wk later. In both groups, no clinically relevant changes were observed either for the gastrointestinal quality of life index or HAD score. Thus, these results suggest that sub-grouping of IBS patients may be important for optimizing treatment responses by the physician. CONCLUSION This pilot study suggests that LCR35 could have some efficacy in IBS patients complaining of diarrhoea. These preliminary results need to be confirmed in larger studies.