Long-Term Effects of a Web-Based Low-FODMAP Diet Versus Probiotic Treatment for Irritable Bowel Syndrome, Including Shotgun Analyses of Microbiota: Randomized, Double-Crossover Clinical Trial.

BACKGROUND: The long-term management of irritable bowel syndrome (IBS) poses many challenges. In short-term studies, eHealth interventions have been demonstrated to be safe and practical for at-home monitoring of the effects of probiotic treatments and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). IBS has been linked to alterations in the microbiota. OBJECTIVE: The aim of this study was to determine whether a web-based low-FODMAP diet (LFD) intervention and probiotic treatment were equally good at reducing IBS symptoms, and whether the response to treatments could be explained by patients' microbiota. METHODS: Adult IBS patients were enrolled in an open-label, randomized crossover trial (for nonresponders) with 1 year of follow-up using the web application IBS Constant Care (IBS CC). Patients were recruited from the outpatient clinic at the Department of Gastroenterology, North Zealand University Hospital, Denmark. Patients received either VSL#3 for 4 weeks (2 × 450 billion colony-forming units per day) or were placed on an LFD for 4 weeks. Patients responding to the LFD were reintroduced to foods high in FODMAPs, and probiotic responders received treatments whenever they experienced a flare-up of symptoms. Treatment response and symptom flare-ups were defined as a reduction or increase, respectively, of at least 50 points on the IBS Severity Scoring System (IBS-SSS). Web-based ward rounds were performed daily by the study investigator. Fecal microbiota were analyzed by shotgun metagenomic sequencing (at least 10 million 2 × 100 bp paired-end sequencing reads per sample). RESULTS: A total of 34 IBS patients without comorbidities and 6 healthy controls were enrolled in the study. Taken from participating subjects, 180 fecal samples were analyzed for their microbiota composition. Out of 21 IBS patients, 12 (57%) responded to the LFD and 8 (38%) completed the reintroduction of FODMAPs. Out of 21 patients, 13 (62%) responded to their first treatment of VSL#3 and 7 (33%) responded to multiple VSL#3 treatments. A median of 3 (IQR 2.25-3.75) probiotic treatments were needed for sustained symptom control. LFD responders were reintroduced to a median of 14.50 (IQR 7.25-21.75) high-FODMAP items. No significant difference in the median reduction of IBS-SSS for LFD versus probiotic responders was observed, where for LFD it was -126.50 (IQR -196.75 to -76.75) and for VSL#3 it was -130.00 (IQR -211.00 to -70.50; P>.99). Responses to either of the two treatments were not able to be predicted using patients' microbiota. CONCLUSIONS: The web-based LFD intervention and probiotic treatment were equally efficacious in managing IBS symptoms. The response to treatments could not be explained by the composition of the microbiota. The IBS CC web application was shown to be practical, safe, and useful for clinical decision making in the long-term management of IBS. Although this study was underpowered, findings from this study warrant further research in a larger sample of patients with IBS to confirm these long-term outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03586622; https://clinicaltrials.gov/ct2/show/NCT03586622.

Costs of electronic health vs. standard care management of inflammatory bowel disease across three years of follow-up-a Danish register-based study.

BACKGROUND: Costs of using eHealth in inflammatory bowel disease (IBD) management has only been assessed for short follow-up periods. The primary aim was to compare the direct costs of eHealth (cases) relative to standard care (matched controls) for IBD during three years of follow-up. METHODS: The study design was a retrospective, registry-based follow-up study of patients diagnosed with IBD two years prior, and three years subsequent, to their enrolment in eHealth. Cases were matched 1:4 with controls receiving standard care based on diagnosis, gender, biologics (yes/no) and age (+/- 5 years). RESULTS: We identified 116 cases (76 (66%) with ulcerative colitis (UC) and 40 (34%) with Crohn's disease (CD)) and matched them with 433 controls. IBD-related outpatient costs were only significantly higher for cases in the year of their inclusion in eHealth (€2,949 vs. €1,621 per patient, p =.01). Mean IBD-related admission costs tended to fall after enrolment in eHealth, with mean admission costs per patient at year 3 of follow-up of €74 for cases and €383 for controls (p = .02). Linear extrapolation of the reduction in costs beyond year 3 after enrolment in eHealth revealed that eHealth would be cost neutral or saving, relative to standard care, from year 4. CONCLUSION: IBD-related outpatient costs in both groups were similar and only significantly higher for cases in the year of their enrolment in eHealth, with admission costs typically falling after a patient's inclusion in eHealth. Estimation revealed eHealth to be cost neutral or saving from year 4.

Occurrence of Colorectal Cancer and the Influence of Medical Treatment in Patients With Inflammatory Bowel Disease: A Danish Nationwide Cohort Study, 1997 to 2015.

BACKGROUND: The risk of colorectal cancer (CRC) for patients with inflammatory bowel disease (IBD) has previously been investigated with conflicting results. We aimed to investigate the incidence and risk of CRC in IBD, focusing on its modification by treatment. METHODS: All patients with incident IBD (n = 35,908) recorded in the Danish National Patient Register between 1997 and 2015 (ulcerative colitis: n = 24,102; Crohn's disease: n = 9739; IBD unclassified: n = 2067) were matched to approximately 50 reference individuals (n = 1,688,877). CRC occurring after the index date was captured from the Danish Cancer Registry. Exposure to medical treatment was divided into categories including none, systemic 5-aminosalicylates, immunomodulators, and biologic treatment. The association between IBD and subsequent CRC was investigated by Cox regression and Kaplan-Meier estimates. RESULTS: Of the IBD patients, 330 were diagnosed with CRC, resulting in a hazard ratio (HR) of 1.15 (95% confidence interval [CI], 1.03-1.28) as compared with the reference individuals. However, when excluding patients diagnosed with CRC within 6 months of their IBD diagnosis, the HR decreased to 0.80 (95% CI, 0.71-0.92). Patients with ulcerative colitis receiving any medical treatment were at significantly higher risk of developing CRC than patients with ulcerative colitis who were not given medical treatment (HR, 1.35; 95% CI, 1.01-1.81), whereas a similar effect of medical treatment was not observed in patients with Crohn's disease or IBD unclassified. CONCLUSIONS: Medical treatment does not appear to affect the risk of CRC in patients with IBD. The overall risk of developing CRC is significantly increased in patients with IBD as compared with the general population. However, when excluding patients diagnosed with CRC within 6 months of their IBD diagnosis, the elevated risk disappears.

eHealth: Disease activity measures are related to the faecal gut microbiota in adult patients with ulcerative colitis.

BACKGROUND/AIM: Microbial dysbiosis in inflammatory bowel disease (IBD) is poorly understood. Faecal samples collected for the purposes of microbiota analysis are not yet a part of everyday clinical practice. To explore associations between faecal microbiota and disease activity measures in adult IBD patients, for the purpose of possibly integrating microbiota measures in an existing IBD eHealth application for disease-monitoring. METHODS: We collected faecal samples from adult IBD patients for one year while they were home-monitoring for disease activity, using faecal calprotectin (FC) and the Simple Clinical Colitis Activity Index (SCCAI). Faecal samples were analysed in two different ways: commercially available test consisting of 54 pre-determined bacterial markers (DNA test) and 16S rRNA gene sequencing (16S-seq). Univariable linear mixed effect models were fitted to predict disease scores using normalised relative abundances as fixed effects. RESULTS: Seventy-eight IBD patients provided a total of 288 faecal samples for microbiota analysis. Two hundred and thirty-four of the samples were from patients with ulcerative colitis (UC). Peptostreptococcus anaerobius was found to correlate significantly with increasing FC, while an additional 24 genera were found to be associated with FC and/or SCCAI (16S-seq). Bacterial markers (DNA test) for Proteobacteria, Shigella spp. and Escherichia spp., were significantly correlated with increasing FC measures, while another 14 markers were found to be associated with FC and/or SCCAI. CONCLUSIONS: In patients with UC, results of both methods are associated with disease activity, correlating significantly with Peptostretococcus anaerobius (16S-seq) and with Proteobacteria, Shigella spp. and Escherichia spp. (DNA test).

Incidence and Prevalence of Microscopic Colitis Between 2001 and 2016: A Danish Nationwide Cohort Study.

BACKGROUND AND AIMS: Epidemiological studies suggest an increasing global incidence of microscopic colitis, including collagenous colitis and lymphocytic colitis. We aimed to investigate the incidence and prevalence of microscopic colitis in Denmark. METHODS: In a nationwide cohort study, we included all incident patients with a recorded diagnosis of collagenous colitis or lymphocytic colitis in the Danish Pathology Register between 2001 and 2016. RESULTS: A total of 14 302 patients with microscopic colitis-8437 [59%] with collagenous and 5865 [41%] with lymphocytic colitis-were identified during the study period. The prevalence in December 2016 was estimated to be 197.9 cases per 100 000 inhabitants. Microscopic colitis was more prevalent among females (n = 10 127 [71%]), with a mean annual incidence of 28.8, compared with 12.3 per 100 000 person-years among males. The overall mean incidence during the study period was 20.7 per 100 000 person-years. Mean age at time of diagnosis was 65 years (standard deviation [SD]:14) for microscopic colitis, 67 [SD:13] for collagenous colitis, and 63 [SD:15] for lymphocytic colitis. The overall incidence increased significantly from 2.3 cases in 2001 to 24.3 cases per 100 000 person-years in 2016. However, the highest observed incidence of microscopic colitis was 32.3 cases per 100 000 person-years in 2011. Large regional differences were found, with the highest incidence observed in the least populated region. CONCLUSIONS: The incidence of microscopic colitis in Denmark has increased 10-fold during the past 15 years and has now surpassed that of Crohn's disease and ulcerative colitis. However, incidence has stabilised since 2012, suggesting that a plateau has been reached.

[Telemedicine applications for monitoring inflammatory bowel disease and irritable bowel syndrome].

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are chronic relapsing diseases with major impact on the patients' everyday life, and increasing incidences affect the burden on the healthcare system. This review summarises the evidence of telemedicine applications (TA) to patients suffering from IBD and IBS in Denmark and abroad. TA have been shown to: reduce time-to-remission, increase quality of life and medical adherence, and reduce hospital admissions and outpatient visits in adult patients with IBD. In paediatric patients with IBD, TA have been shown to reduce: the need of outpatient visits, the number of school absences, and the symptom scores.

Individualized home-monitoring of disease activity in adult patients with inflammatory bowel disease can be recommended in clinical practice: A randomized-clinical trial.

BACKGROUND: The optimal way to home-monitor patients with inflammatory bowel disease (IBD) for disease progression or relapse remains to be found. AIM: To determine whether an electronic health (eHealth) screening procedure for disease activity in IBD should be implemented in clinical practice, scheduled every third month (3M) or according to patient own decision, on demand (OD). METHODS: Adult IBD patients were consecutively randomized to 1-year open-label eHealth interventions (3M vs OD). Both intervention arms were screening for disease activity, quality of life and fatigue and were measuring medical compliance with the constant care web-application according to the screening interventions OD or 3M. Disease activity was assessed using home measured fecal calprotectin (FC) and a disease activity score. RESULTS: In total, 102 patients were randomized (n = 52/50 3M/OD) at baseline, and 88 patients completed the 1-year study (n = 43 3M; n = 45 OD). No difference in the two screening procedures could be found regarding medical compliance (P = 0.58), fatigue (P = 0.86), quality of life (P = 0.17), mean time spent in remission (P > 0.32), overall FC relapse rates (P = 0.49), FC disease courses (P = 0.61), FC time to a severe relapse (P = 0.69) and remission (P = 0.88) during 1 year. Median (interquartile range) numbers of FC home-monitoring test-kits used per patient were significantly different, 3M: 6.0 (5.0-8.0) and OD: 4.0 (2.0-9.0), P = 0.04. CONCLUSION: The two eHealth screening procedures are equally good in capturing a relapse and bringing about remission. However, the OD group used fewer FC home test-kits per patient. Individualized screening procedures can be recommended for adult IBD patients in clinical web-practice.

Low-FODMAP diet reduces irritable bowel symptoms in patients with inflammatory bowel disease.

AIM: To investigate the effect of a low-FODMAP diet on irritable bowel syndrome (IBS)-like symptoms in patients with inflammatory bowel disease (IBD). METHODS: This was a randomised controlled open-label trial of patients with IBD in remission or with mild-to-moderate disease and coexisting IBS-like symptoms (Rome III) randomly assigned to a Low-FODMAP diet (LFD) or a normal diet (ND) for 6 wk between June 2012 and December 2013. Patients completed the IBS symptom severity system (IBS-SSS) and short IBD quality of life questionnaire (SIBDQ) at weeks 0 and 6. The primary end-point was response rates (at least 50-point reduction) in IBS-SSS at week 6 between groups; secondary end-point was the impact on quality of life. RESULTS: Eighty-nine patients, 67 (75%) women, median age 40, range 20-70 years were randomised: 44 to LFD group and 45 to ND, from which 78 patients completed the study period and were included in the final analysis (37 LFD and 41 ND). There was a significantly larger proportion of responders in the LFD group (n = 30, 81%) than in the ND group (n = 19, 46%); (OR = 5.30; 95%CI: 1.81-15.55, P < 0.01). At week 6, the LFD group showed a significantly lower median IBS-SSS (median 115; inter-quartile range [IQR] 33-169) than ND group (median 170, IQR 91-288), P = 0.02. Furthermore, the LFD group had a significantly greater increase in SIBDQ (median 60, IQR 51-65) than the ND group (median 50, IQR 39-60), P < 0.01. CONCLUSION: In a prospective study, a low-FODMAP diet reduced IBS-like symptoms and increased quality of life in patients with IBD in remission.

Using eHealth strategies in delivering dietary and other therapies in patients with irritable bowel syndrome and inflammatory bowel disease.

Health-care systems around the world are facing increasing costs. Non-adherent, chronically ill patients are one such expense incurred by health-care providers. Web-based home-monitoring of patients-or eHealth-has been shown to increase adherence to medical therapy, facilitate contact between patients and health-care professionals, and reduce time to remission for patients with inflammatory bowel disease (IBD). Web-based treatment is a supportive tool for the health-care provider in an out-patient clinic. eHealth web-programs, such as the Constant Care application, visualize disease activity in a traffic light system and empower patients to screen for disease activity, enabling them to respond appropriately to their symptoms. The eHealth screening procedure for monitoring both pediatric and adult IBD patients is based on a self-obtained symptom score, together with a fecal biomarker for inflammation (fecal calprotectin) that the patients can measure independently using their smart phone, providing both patient and physician with an immediate disease status that they can react to instantaneously. Likewise, web applications for IBD patients, web applications for irritable bowel syndrome (IBS) patients and also IBD patients with co-existing IBS, have proven valuable for monitoring and treating IBS symptoms with a diet low in fermentable oligo-, di-, monosaccharides and polyols (low-FODMAP diet). With careful disease monitoring via the web application and increased patient adherence, eHealth might be capable of improving the natural disease course of IBD and IBS.

Ehealth: low FODMAP diet vs Lactobacillus rhamnosus GG in irritable bowel syndrome.

AIM: To investigate the effects of a low fermentable, oligosaccharides, disaccharides, monosaccharides and polyols diet (LFD) and the probiotic Lactobacillus rhamnosus GG (LGG) in irritable bowel syndrome (IBS). METHODS: Randomised, unblinded controlled trial on the effect of 6-wk treatment with LFD, LGG or a normal Danish/Western diet (ND) in patients with IBS fulfilling Rome III diagnostic criteria, recruited between November 2009 and April 2013. Patients were required to complete on a weekly basis the IBS severity score system (IBS-SSS) and IBS quality of life (IBS-QOL) questionnaires in a specially developed IBS web self-monitoring application. We investigated whether LFD or LGG could reduce IBS-SSS and improve QOL in IBS patients. RESULTS: One hundred twenty-three patients (median age 37 years, range: 18-74 years), 90 (73%) females were randomised: 42 to LFD, 41 to LGG and 40 to ND. A significant reduction in mean ± SD of IBS-SSS from baseline to week 6 between LFD vs LGG vs ND was revealed: 133 ± 122 vs 68 ± 107, 133 ± 122 vs 34 ± 95, P < 0.01. Adjusted changes of IBS-SSS for baseline covariates showed statistically significant reduction of IBS-SSS in LFD group compared to ND (IBS-SSS score 75; 95%CI: 24-126, P < 0.01), but not in LGG compared to ND (IBS-SSS score 32; 95%CI: 18-80, P = 0.20). IBS-QOL was not altered significantly in any of the three groups: mean ± SD in LFD 8 ± 18 vs LGG 7 ± 17, LFD 8 ± 18 vs ND 0.1 ± 15, P = 0.13. CONCLUSION: Both LFD and LGG are efficatious in patients with IBS.

Ehealth monitoring in irritable bowel syndrome patients treated with low fermentable oligo-, di-, mono-saccharides and polyols diet.

In the present study we report on changes in irritable bowel syndrome-severity scoring system (IBS-SSS) and irritable bowel syndrome-quality of life (IBS-QoL) in 19 IBS patients, aged 18 to 74 years (F/M: 14/5), during 12 wk registering their symptoms on the web-application (www.ibs.constant-care.dk). During a control period of the first 6-wk patients were asked to register their IBS-SSS and IBS-QoL on the web-application weekly without receiving any intervention. Thereafter, low fermentable oligo-, di-, mono-saccharides and polyols (FODMAP) diet (LFD) was introduced for the next 6 wk while continuing the registration. Though a small sample size a significant improvement in disease activity (IBS-SSS) was observed during both the control period, median: 278 (range: 122-377), P = 0.02, and subsequently during the LFD period, median: 151 (range: 29-334), P < 0.01. The IBS-QoL solely changed significantly during the LFD period, median: 67 (37-120), P < 0.01. The significant reduction in disease activity during the control period shows a positive effect of the web-application on IBS symptoms when presented as a "traffic light". However adding the diet reduced IBS-SSS to < 150, inactive to mild symptoms. In the future results from larger scale trials are awaited.