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Summary Background The Crohn's disease exclusion diet (CDED) with partial enteral nutrition is effective for induction of remission in children with mild-to-moderate Crohn's disease. We aimed to assess the CDED in adults with Crohn's disease. Methods We did an open-label, pilot randomised trial at three medical centres in Israel. Eligible patients were biologic naive adults aged 18–55 years with mild-to-moderate Crohn's disease (defined by a Harvey–Bradshaw Index score of 5–14 points), a maximal disease duration of 5 years, with active disease on colonoscopy, or imaging with elevated inflammatory markers (C-reactive protein >5 mg/L or faecal calprotectin concentration >200 μ/g). Patients were randomly assigned (1:1) to CDED plus partial enteral nutrition or CDED alone for 24 weeks. Randomisation was via block randomisation (block sizes of six) using sealed, numbered, and opaque envelopes. Patients and investigators were aware of which group patients were assigned to due to the nature of the different interventions. The primary endpoint was clinical remission, defined as a Harvey–Bradshaw Index score of less than 5 at week 6. The primary endpoint was assessed in the intention-to-treat (ITT) population, which included all patients who used the dietary therapy for at least 48 h. We report results of the final analysis. This trial is registered with ClinicalTrials.gov , NCT02231814 . Findings Between Jan 12, 2017, and May 11, 2020, 91 patients were screened, of whom 44 were randomly assigned to the CDED plus partial enteral nutrition group (n=20) or CDED alone group (n=24). 19 patients in the CDED plus partial enteral nutrition group and 21 patients in the CDED alone group received the allocated intervention for at least 48 h and thus were included in the ITT analysis. At week 6, 13 (68%) of 19 patients in the CDED plus partial enteral nutrition group and 12 (57%) of 21 patients in the CDED group had achieved clinical remission (p=0·4618). Among the 25 patients in remission at week 6, 20 (80%) were in sustained remission at week 24 (12 patients in the CDED plus partial enteral nutrition group and eight in the CDED alone group). 14 (35%) of 40 patients were in endoscopic remission at week 24 (eight patients in the CDED plus partial enteral nutrition group and six in the CDED alone group). No serious adverse events or treatment-related adverse events were reported in either group. Interpretation CDED with or without partial enteral nutrition was effective for induction and maintenance of remission in adults with mild-to-moderate biologic naive Crohn's disease and might lead to endoscopic remission. These data suggest that CDED could be used for mild-to-moderate active Crohn's disease and should be assessed in a powered randomised controlled trial. Funding Azrieli Foundation and Nestle Health Science.

Background: The effectiveness of anti-TNF or ustekinumab (UST) as a second-line biologic after vedolizumab (VDZ) failure has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, We aim to investigate the effectiveness of anti-TNF and UST as second-line therapy in patients with Crohn’s disease (CD) who failed VDZ as a first-line treatment. The primary outcome was clinical response at week 16–22. Secondary outcomes included the rates of clinical remission, steroid-free clinical remission, CRP normalization, and adverse events. Results: Fifty-nine patients who failed on VDZ as a first-line treatment for CD were included; 52.8% patients received anti-TNF and 47.2% UST as a second-line therapy. In initial period (Week 16–22), the clinical response and remission rate was similar between both groups: 61.2% vs. 68%, p = 0.8 and 48.3% vs. 56%, p = 0.8 on anti-TNF and UST therapy, respectively. Furthermore, in the maintenance period the rate was similar: 75% vs. 82.3%, p = 0.8 and 62.5% vs. 70.5%, p = 0.8, respectively. Of the patients, 12 out of the 59 stopped the therapy, without a significant difference between the two groups (p = 0.6). Conclusion: Second-line biological therapy after VDZ failure therapy was effective in >60% of the patients with CD. No differences in effectiveness were detected between the use of anti-TNF and UST as a second line.

BACKGROUND QingDai (QD, Indigo) was shown to be effective for ulcerative colitis (UC) in randomized controlled trials and retrospective reports from Japan. However, experience with QD for UC in the West is extremely limited. We aimed to describe the effectiveness and safety of QD in a national cohort of patients with UC followed at tertiary referral centers in Israel. METHODS A retrospective study. We included adult patients who received QD for active UC (simple colitis clinical activity index (SCCAI)≥3) between 2018 -2022 at five academic centers. A majority of patients received QD in a combination with curcumin (CurQD). The primary outcome was clinical response at the end of induction (defined as the last follow-up visit between weeks 8 to 16 from the start of the treatment). Clinical response was defined as an improvement of SCCAI≥ 3 points; clinical remission as SCCAI≤2. C-reactive protein (CRP), fecal calprotectin (FC) levels and endoscopic Mayo score before and after treatment were compared when available. Starting corticosteroid or biologic treatment, hospitalization due to disease exacerbation, colectomy, discontinuation of treatment due to an adverse event or missing follow-up data were considered treatment failures RESULTS A total of 82 patients were included [median age-32, interquartile ratio (IQR)-23-41), 47 (57.3%) female; disease extent- 16 (20.5%)-proctitis, 28 (35.9%)- left-sided, 34 (43.6%) – pancolitis]. At treatment onset, 27 (41.5%) were treated with corticosteroids and 28 (34.1%) with a biologic or small molecule, 10 (12.9%) failed ≥ 3 biologics or small molecules. Median SCCAI was 6 (5-9), CRP- 5 (2-17) mg/L, fecal calprotectin levels – 698 (320 -1190) mg/g and endoscopic Mayo score- 2. QD was initiated in combination with curcumin (CurQD) in 77 (95.1%) of the patients. The last induction follow-up occurred after a median of 8 (8-12) weeks. At the end of induction, 64 (78%) responded to treatment, including 52 (63.4%) that achieved clinical remission (figure 1). At the end of induction, median SCCAI was 2 (1-3) (p CONCLUSIONS In this multicenter retrospective cohort study, QD treatment (predominantly as combination CurQD) was effective for induction of clinical response and remission in active UC patients, including biologic-experienced patients. All adverse events were mild and resolved either spontaneously or after QD discontinuation. Our results suggest QD as a potential effective and safe agent for induction of response and remission in patients with active UC.

BACKGROUND The herbal extracts Curcumin and QingDai were previously shown to be effective in mild-moderate and in moderate-severe ulcerative colitis (UC), respectively. We evaluated the efficacy and safety of a combination of curcumin-QingDai (CurQD) in patients with active UC. METHODS This was a two parts trial. Part 1 was an open label study of 4 weeks CurQD in patients with active UC, defined by a Simple Clinical Colitis Activity Index (SCCAI) score ≥5 and a modified Mayo endoscopic sub-score≥2. Part 2 was a placebo-controlled trial conducted in two centers in Israel and Greece, that randomized active UC patients at a 2:1 ratio to either enteric-coated CurQD 3gr/day or an identical placebo for eight weeks. The co-primary outcome at week 8 was clinical response (reduction in SCCAI of ≥3 points) and an objective evidence of response (Mayo endoscopic subscore improvement of ≥1 or 50% calprotectin reduction from baseline). Responding patients continued either Curcumin or placebo alone for additional 8 weeks as maintenance treatment. Expression of Cyp1A1 in rectal mucosa was assessed as a measure of aryl-hydrocarbon receptor (AhR) pathway activation. Curcumin purity, and indigo and indirubin content in CurQD were confirmed by LC-MS/MS. RESULTS 59 patients were enrolled in the two study parts. In efficacy analysis of part 1, 7/10 responded including 3/10 who achieved clinical remission. For part 2, 95 patients were screened and 42 were included and randomized. The co-primary outcome was achieved in 43% and 8% of CurQD and placebo patients, respectively (p=0.033). Clinical response was observed in 85.7% versus 30.7% (p CONCLUSION In this randomized controlled trial, combination CurQD was found to be effective for inducing remission in active UC patients. Induction of AhR may merit further study as a potential treatment target in active UC.

IntroductionPouchitis, often developing after colectomy and ileal pouch-anal anastomosis for ulcerative colitis, is highly responsive to antibiotics. Ciprofloxacin and/or metronidazole are commonly used, often for prolonged periods. We report patterns of antibiotic use, adverse events, and resistant infections in patients with pouchitis with long-term antibiotic treatment.MethodsIn a cohort of patients following pouch surgery, a retrospective nested case-control analysis was performed between 2010 and 2017. Ultra-long-term use, defined as the top 10% of users, was compared with the remaining users. Patterns of antibiotic use, adverse events, and resistant infections were analyzed.ResultsThe cohort included 205 patients with UC, of whom 167 (81.5%) used antibiotics for pouchitis, predominantly ciprofloxacin. The long-term antibiotic use rate was 18% and 42% at 5 and 20 years postsurgery, respectively. Mean antibiotic use of at least 1, 3, and 6 months/year was noted in 54 (26.3%), 31 (15.1%), and 14 (6.8%) patients, respectively. Twenty-two (13.2%) and 4 (2.4%) patients reported mild and severe (transient) adverse events, respectively, without mortalities, tendinopathies or arrhythmias. Adverse event rates for ciprofloxacin and metronidazole were 1per 10,000 and 6 per 10,000 use-days, respectively. Longer, but not ultra-long antibiotic use, was associated with mild adverse events. There was no association between antibiotic use and resistant infections. Thirteen (6.3%) patients required ileostomy procedures—more commonly in the ultra-long-term antibiotic users.ConclusionsPatients with pouchitis may require prolonged antibiotic treatment, reflecting clinical benefit and favorable safety profile. Few adverse events and resistant infections were observed with long-term antibiotics use. However, resistant microbial strains selection, which are potentially transmittable, warrants consideration of different therapeutic alternatives.

Background We evaluated whether integration of novel diets for donors and patients, in addition to faecal transplantation [FT], could increase FT remission rate in refractory ulcerative colitis [UC]. Methods This was a blinded, randomised, controlled trial in adults with active UC, defined by a simple clinical colitis activity index [SCCAI] of ≥5 and ≤11 and endoscopic Mayo score 2–3, refractory to medication. Group 1 received free diet and single donor standard FT by colonoscopy on Day 1and rectal enemas on Days 2 and 14 without dietary conditioning of the donor. Group 2 received FT as above but with dietary pre-conditioning of the donor for 14 days and a UC Exclusion Diet [UCED] for the patients. Group 3 received the UCED alone. The primary endpoint was Week 8 clinical steroid-free remission, defined as SCCAI Results Of 96 planned patients, 62 were enrolled. Remission Week 8 Group 1 was 2/17 [11.8%], Group 2 was 4/19 [21.1%], Group 3 was 6/15 [40%] [non-significant]. Endoscopic remission Group 1 was 2/17 [12%], Group 2 was 3/19 [16%], Group 3 was 4/15 [27%] [Group 1 vs 3 p = 0.38]. Mucosal healing [Mayo 0] was achieved only in Group 3 [3/15, 20%] vs 0/36 FT patients [p = 0.022]. Exacerbation of disease occurred in 3/17 [17.6%] of Group 1, 4/19 [21.1%] of Group 2, and 1/15 [6.7%] of Group 3 [Group 2 vs 3, p = 0.35]. Conclusions UCED alone appeared to achieve higher clinical remission and mucosal healing than single donor FT with or without diet. The study was stopped for futility by a safety monitoring board.

An early treat-to-target approach in Crohn’s disease (CD) patients is recommended to avoid complications. However, CD may not always progress despite lack of treatment, thus exposing some patients to unnecessary side effects. We aimed to examine whether newly diagnosed CD patients with an inflammatory phenotype can benefit from a watchful waiting approach. This retrospective cohort study followed CD patients with an inflammatory phenotype who were diagnosed between 2010 and 2015 and followed for at least 1 year. A watchful waiting approach was defined as maintenance therapy with 5-ASA medication only or no treatment during the first year of diagnosis or longer. Disease complications were defined as need for surgery or change in disease phenotype. Eighty-six patients were included and followed-up for 57.0 ± 29.0 months. Thirty-seven patients were managed with a watchful waiting approach and 49 with an early therapeutic intervention. The majority of patients (83.8%) in the watchful waiting group did not develop disease complications. In this group, there was no difference in clinical disease severity (stools per day, 2.7 ± 1.7 vs 3.3 ± 1.0, P = 0.39; abdominal pain, 74.2 vs 50.0%, P = 0.24) between those who did not develop complications and those who did. Smoking was associated with a complicated course (multivariate analysis: OR = 1.98, 95% CI 1.06–3.71, P = 0.03). A watchful waiting approach of newly diagnosed CD patients with an inflammatory phenotype may be a feasible option, with low long-term complication rate specifically in nonsmoking patients.

Restorative proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of choice for patients with ulcerative colitis.

Background Endoscopic-post-operative-recurrence [ePOR] in Crohn’s disease [CD] after ileocecal resection [ICR] is a major concern. We aimed to evaluate the effectiveness of early prophylaxis with biologics and to compare anti-tumour necrosis factor [anti-TNF] therapy to vedolizumab [VDZ] and ustekinumab [UST] in a real-world setting. Methods A retrospective multicentre study of CD-adults after curative ICR on early prophylaxis was undertaken. ePOR was defined as a Rutgeerts score [RS] ≥ i2 or colonic-segmental-SES-CD ≥ 6. Multivariable logistic regression was used to evaluate risk factors, and inverse probability treatment weighting [IPTW] was applied to compare the effectiveness between agents. Results The study included 297 patients (53.9% males, age at diagnosis 24 years [19–32], age at ICR 34 years [26–43], 18.5% smokers, 27.6% biologic-naïve, 65.7% anti-TNF experienced, 28.6% two or more biologics and 17.2% previous surgery). Overall, 224, 39 and 34 patients received anti-TNF, VDZ or UST, respectively. Patients treated with VDZ and UST were more biologic experienced with higher rates of previous surgery. ePOR rates within 1 year were 41.8%. ePOR rates by treatment groups were: anti-TNF 40.2%, VDZ 33% and UST 61.8%. Risk factors for ePOR at 1 year were: past-infliximab (adjusted odds ratio [adj.OR] = 1.73 [95% confidence interval, CI: 1.01–2.97]), past-adalimumab [adj.OR = 2.32 [95% CI: 1.35-4.01] and surgical aspects. After IPTW, the risk of ePOR within 1 year of VDZ vs anti-TNF or UST vs anti-TNF was comparable (OR = 0.55 [95% CI: 0.25–1.19], OR = 1.86 [95% CI: 0.79–4.38]), respectively. Conclusion Prevention of ePOR within 1 year after surgery was successful in ~60% of patients. Patients treated with VDZ or UST consisted of a more refractory group. After controlling for confounders, no differences in ePOR risk were seen between anti-TNF prophylaxis and other groups.

BACKGROUND AND AIMS: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators.METHODS: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment.RESULTS: A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia.CONCLUSIONS: I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258).

Atopic dermatitis (AD) is a remitting relapsing chronic eczematous pruritic disease. Several studies suggest that gut microbiota may influence AD by immune system regulation.We performed the first in-human efficacy and safety assessment of fecal microbiota transplantation (FMT) for AD adult patients. All patients received 2 placebo transplantations followed by 4 FMTs each 2 weeks apart. AD severity and fecal microbiome profile were evaluated by the Scoring Atopic Dermatitis Score (SCORAD), the weekly frequency of topical corticosteroids usage, and gut microbiota metagenomic analysis, at the study beginning, before every FMT, and 1-8 months after the last FMT.Nine patients completed the study protocol. There was no significant change in the SCORAD score following the two placebo transplants. The average SCORAD score significantly decreased from baseline at Weeks 4-12 (before and 2 weeks after 4 times of FMT) (59.2 ± 34.9%, Wilcoxon p = .011), 50% and 75% decrease was achieved by 7 (77%) and 4 (44%) patients, respectively. At Week 18 (8 weeks after the last FMT) the average SCORAD score decreased from baseline at Week 4 (85.5 ± 8.4%, Wilcoxon p = .018), 50% and 75% decrease was achieved by 7 (77%) and 6 (66.7%) patients respectively. Weekly topical corticosteroids usage was diminished during the study and follow-up period as well. Two patients had a quick relapse and were switched to a different treatment. Two patients developed exacerbations alleviated after an additional fifth FMT. Metagenomic analysis of the fecal microbiota of patients and donors showed bacterial strains transmission from donors to patients. No adverse events were recorded during the study and follow-up period.FMT may be a safe and effective therapeutic intervention for AD patients, associated with transfer of specific microbial species from the donors to the patients. Further studies are required to reconfirm these results.

We sought to define the effectiveness and safety of tofacitinib in a real-world (RW) cohort of Israeli patients with moderate to severe ulcerative colitis (UC).This was a multi-center retrospective observational cohort study (2019-2020) to assess the effectiveness and safety of tofacitinib induction and maintenance therapy up to 26 weeks. Clinical response and remission were defined as a reduction in Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) of ≥3 points, and SCCAI ≤2 or a PMS ≤1, respectively.We included 73 patients, 47% male; median age 26 years [IQR: 19.5-39.5], disease duration 7 years [IQR: 2.5-14.5], follow-up 7.1 months [IQR: 3-12], 91% biologics-experienced, and 74% ≥ 2-biologics. Half of patients used concomitant corticosteroids (CS). Overall, 56.1% discontinued therapy due to either lack of response and/or adverse events (AEs), median time to discontinuation - 9.7 months [IQR 3.4-16]. Overall, response, remission, and CS-free-remission were achieved in 47.6%, 20.6%, and 17.5% of patients, respectively. At early maintenance (week 26), response, remission, and CS-free-remission were achieved in 65%, 22.5%, and 20% of patients, respectively. At week 26, tofacitinib 10 mg BID was still used in 43%. Seventeen patients (23.2%) had an adverse event including herpes zoster- 2.7%, hospitalization- 12.3%, and colectomy- 2.7%.Tofacitinib was effective in achieving CS-free-remission in about 1/5 of highly biologics -experienced patients with UC. Despite a considerable proportion of patients maintained on tofacitinib 10 mg bid, it was well tolerated and safe. Earlier positioning of tofacitinib in the therapeutic algorithm may result in improved outcomes.

Educating patients regarding thier inflammatory bowel disease (IBD) is important for their empowerment and disease management. We aimed to develop a questionnaire to evaluate patient understanding and knowledge of IBD.We have developed the Understanding IBD Questionnaires (U-IBDQ), consisting of multiple-choice questions in two versions [for Crohn's disease (CD) and ulcerative colitis (UC)]. The questionnaires were tested for content and face validity, readability, responsiveness and reliability. Convergent validity was assessed by correlating the U-IBDQ score with physician's subjective assessment scores. Discriminant validity was assessed by comparison to healthy controls (HC), patients with chronic gastrointestinal (GI) conditions other than IBD, and to GI nurses. Multivariate analysis was performed to determine factors associated with a high level of disease understanding.The study population consisted of IBD patients (n = 106), HC (n = 35), chronic GI disease patients (n = 38) and GI nurses (n = 19). Mean U-IBDQ score among IBD patients was 56.5 ± 21.9, similar for CD and UC patients (P = 0.941), but significantly higher than that of HC and chronic GI disease patients and lower than that of GI nurses (P 0.001), supporting its discriminant validity. The U-IBDQ score correlated with physician's subjective score (r = 0.747, P 0.001) and was found to be reliable (intra-class correlation coefficient = 0.867 P 0.001). Independent factors associated with high U-IBDQ scores included academic education (OR = 1.21, 95% CI 1.10-1.33, P 0.001), biologic therapy experience (OR = 1.24, 95% CI 1.01-1.53, P = 0.046), and IBD diagnosis at21 years of age (OR = 2.97, 95% CI 1.05-8.87, P = 0.050).The U-IBDQ is a validated, reliable and short, self-reported questionnaire that can be used for assessing understanding of disease pathophysiology and treatment by IBD patients.

Human gut commensals are increasingly suggested to impact non-communicable diseases, such as inflammatory bowel diseases (IBD), yet their targeted suppression remains a daunting unmet challenge. In four geographically distinct IBD cohorts (n = 537), we identify a clade of Klebsiella pneumoniae (Kp) strains, featuring a unique antibiotics resistance and mobilome signature, to be strongly associated with disease exacerbation and severity. Transfer of clinical IBD-associated Kp strains into colitis-prone, germ-free, and colonized mice enhances intestinal inflammation. Stepwise generation of a lytic five-phage combination, targeting sensitive and resistant IBD-associated Kp clade members through distinct mechanisms, enables effective Kp suppression in colitis-prone mice, driving an attenuated inflammation and disease severity. Proof-of-concept assessment of Kp-targeting phages in an artificial human gut and in healthy volunteers demonstrates gastric acid-dependent phage resilience, safety, and viability in the lower gut. Collectively, we demonstrate the feasibility of orally administered combination phage therapy in avoiding resistance, while effectively inhibiting non-communicable disease-contributing pathobionts.

Data regarding fecal calprotectin (FC), commonly used for noninvasive monitoring in inflammatory bowel diseases, are scarce in patients with ileal pouch-anal anastomosis (IPAA). We aimed to assess the association between FC levels and pouch inflammation in patients with ulcerative colitis who underwent IPAA.A cross-sectional study of adults with ulcerative colitis who underwent IPAA with J-pouch formation prospectively followed in a dedicated pouch clinic. Patients had clinical, endoscopic, and histologic assessments within 90 days of FC sampling. Each patient encounter was evaluated separately. Pouchitis was defined as a Pouchitis Disease Activity Score of ≥7 (maximum score: 18).Overall, 156 patients had 296 encounters that met inclusion criteria. A total of 52% of patients were male, median age at evaluation was 43 (IQR, 35-58) years, and median pouch age was 10 (interquartile range [IQR], 2.5-15) years. Median FC values were significantly lower in patients without compared with those with pouchitis (208 [IQR, 96-478] μg/g vs 550 [IQR, 250-1051] μg/g; P.0001). Mean FC values increased among patients with higher endoscopic and histologic scores. FC performed better than C-reactive protein as a predictor of pouchitis. FC of460 μg/g had80% specificity for predicting significant endoscopic disease (Pouchitis Disease Activity Score endoscopic subscore ≥5), while an FC of125 μg/g had over 80% specificity in predicting endoscopic remission.FC levels are increased in patients with endoscopic and histologic inflammation of the pouch. FC may be a useful tool in the management of patients following IPAA.

Bariatric surgery is often the preferred method to resolve obesity and diabetes, with ∼800,000 cases worldwide yearly and high outcome variability. The ability to predict the long-term body mass index (BMI) change following surgery has important implications for individuals and the health care system in general. Given the tight connection between eating habits, sugar consumption, BMI, and the gut microbiome, we tested whether the microbiome before any treatment is associated with different treatment outcomes, as well as other intakes (high-density lipoproteins [HDL], triglycerides, etc.). A projection of the gut microbiome composition of obese (sampled before and after bariatric surgery) and lean patients into principal components was performed, and the relation between this projection and surgery outcome was studied. The projection revealed three different microbiome profiles belonging to lean, obese, and obese individuals who underwent bariatric surgery, with the postsurgery microbiome more different from the lean microbiome than the obese microbiome. The same projection allowed for a prediction of BMI loss following bariatric surgery, using only the presurgery microbiome. The microbial changes following surgery were an increase in the relative abundance of Proteobacteria and Fusobacteria and a decrease in Firmicutes. The gut microbiome can be decomposed into main components depicting the patient's development and predicting in advance the outcome. Those may be translated into the better clinical management of obese individuals planning to undergo metabolic surgery. IMPORTANCE BMI and diabetes can affect the gut microbiome composition. Bariatric surgery has large variabilities in the outcome. The microbiome was previously shown to be a good predictor for multiple diseases. We analyzed here the gut microbiome before and after bariatric surgery and showed the following. (i) The microbiome before surgery can be used to predict surgery outcomes. (ii) The postsurgery microbiome drifts further away from the lean microbiome than the microbiome of the presurgery obese patients. These results can lead to a microbiome-based presurgery decision whether to perform surgery.

Background Treatment of inflammatory bowel diseases (IBD) is associated with multiple side effects, such as malignancies and infections, that may be more common in the elderly population. The aim of this study was to compare the safety and efficacy of vedolizumab (VDZ) in young and elderly patients. Methods This is a binational, multicentre, retrospective, case–control study consisting of patients from multiple centres in Israel and from Edinburgh, UK. IBD patients in whom VDZ treatment was initiated during 2015–2019, and were followed for at least 14 weeks, were included in the study according to their age groups: ≤40 years or ≥60 years. Patients were matched for disease duration, classification and severity. Results We recruited 144 patients (82 CD and 62 UC) to the elderly cohort and 140 patients (83 CD and 57 UC) to the young cohort. The respective average age was 70.2 ± 7.3 years and 29.6 ± 5.7 years. Elderly patients had significantly more cardiovascular, metabolic and respiratory co-morbidities and had less prior exposure to anti-TNF agents compared with the young cohort (CD: 51% vs. 88%, p < 0.001; UC: 47% vs. 70%, p = 0.03). Clinical and endoscopic responses were comparable between the groups at Weeks 14 and 52 among elderly and young (Week 52 remission: CD: 40% vs. 35%, p = 0.7; UC: 48% vs. 51%, p = 0.84) (Figure 1). However, the use of more than one anti-TNF agent was an independent predictor of poor response and remission rates to VDZ at all time points among the elderly (OR 0.13; 95% CI 0.03–0.69). A total of 49 adverse events were documented, 23 (16%) in the young cohort and 26 (18%) in the elderly cohort (p = 0.5). Overall there were significantly more infections in the elderly cohort (3 (2%) vs. 17 (12%), p = 0.002) and included nasopharyngeal, urinary, skin and Clostridium difficile infections. None of them was fatal but one patient stopped treatment due to urinary sepsis. There were significantly more non-specific adverse events such as headache and myalgia in the young cohort (8% vs. 2%, p = 0.03). Six patients (4%) in the young cohort required drug discontinuation due to adverse events compared with 4 patients (3%) in the elderly cohort (p = 0.5). The reasons for discontinuation were similar between the groups. Conclusion VDZ is equally effective in elderly and young IBD patients. This study shows an increased risk of overall infections in the elderly cohort, it is unclear whether these are related to VDZ treatment or the age and background diseases of these patients. In elderly patients, the use of VDZ before anti-TNF therapy may improve response and remission rates.

Objectives: Intestinal carriage with extended spectrum β-lactamase Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) can persist for months. We aimed to evaluate whether oral antibiotics followed by faecal microbiota transplantation (FMT) can eradicate intestinal carriage with ESBL-E/CPE.Methods: Randomized, open-label, superiority trial in four tertiary-care centres (Geneva (G), Paris (P), Utrecht (U), Tel Aviv (T)). Non-immunocompromised adult patients were randomized 1: 1 to either no intervention (control) or a 5-day course of oral antibiotics (colistin sulphate 2 × 106 IU 4×/day; neomycin sulphate 500 mg 4×/day) followed by frozen FMT obtained from unrelated healthy donors. The primary outcome was detectable intestinal carriage of ESBL-E/CPE by stool culture 35-48 days after randomization (V4). ClinicalTrials.govNCT02472600. The trial was funded by the European Commission (FP7).Results: Thirty-nine patients (G = 14; P = 16; U = 7; T = 2) colonized by ESBL-E (n = 36) and/or CPE (n = 11) were enrolled between February 2016 and June 2017. In the intention-to-treat analysis 9/22 (41%) patients assigned to the intervention arm were negative for ESBL-E/CPE at V4 (1/22 not receiving the intervention imputed as positive) whereas in the control arm 5/17 (29%) patients were negative (one lost to follow up imputed as negative) resulting in an OR for decolonization success of 1.7 (95% CI 0.4-6.4). Study drugs were well tolerated overall but three patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea (all received FMT).Conclusions: Non-absorbable antibiotics followed by FMT slightly decreased ESBL-E/CPE carriage compared with controls; this difference was not statistically significant, potentially due to early trial termination. Further clinical investigations seem warranted.

Iron deficiency, a common comorbidity of gastrointestinal inflammatory disorders such as inflammatory bowel diseases (IBD), is often treated with oral iron supplementation. However, the safety of oral iron supplementation remains controversial because of its association with exacerbated disease activity in a subset of IBD patients. Because iron modulates bacterial growth and function, one possible mechanism by which iron may exacerbate inflammation in susceptible hosts is by modulating the intestinal microbiota. We, therefore, investigated the impact of dietary iron on the intestinal microbiota, utilizing the conventionalization of germ-free mice as a model of a microbial community in compositional flux to recapitulate the instability of the IBD-associated intestinal microbiota. Our findings demonstrate that altering intestinal iron availability during community assembly modulated the microbiota in non-inflamed wild type (WT) and colitis-susceptible interleukin-10-deficient (Il10−/-) mice. Depletion of luminal iron availability promoted luminal compositional changes associated with dysbiotic states irrespective of host genotype, including an expansion of Enterobacteriaceae such as Escherichia coli. Mechanistic in vitro growth competitions confirmed that high-affinity iron acquisition systems in E. coli enhance its abundance over other bacteria in iron-restricted conditions, thereby enabling pathobiont iron scavenging during dietary iron restriction. In contrast, distinct luminal community assembly was observed with dietary iron supplementation in WT versus Il10−/- mice, suggesting that the effects of increased iron on the microbiota differ with host inflammation status. Taken together, shifts in dietary iron intake during community assembly modulate the ecological structure of the intestinal microbiota and is dependent on host genotype and inflammation status.

Alterations in the gut microbiome have been implicated in the pathogenesis of several immune-mediated inflammatory diseases such as psoriatic arthritis. This work aimed to characterize the gut microbial signature of patients with active psoriasis as compared with age-, body mass index- and comorbidity-matched non-psoriatic controls and to correlate them with differential expression of metabolic pathways. Fecal samples were processed and 16S rRNA was sequenced. PICRUSt was used to perform an analysis of metabolic pathways. Of the 46 participants, 52% (n = 24) suffered from psoriasis. There was a significant difference in β-diversity between the two groups. Psoriatic patients had a significant increase in the Firmicutes and Actinobacteria phyla as compared with matched controls. At the genus level, psoriatic patients had a unique bacterial composition. At the species level, the psoriatic patients showed significant increases in the relative proportions of (false discovery rate

Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn’s disease (CD) failing anti- Tumor necrosis factors (TNFs), however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. Results: Two-hundred and four patients were included, 156/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A), the remaining 48/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16–22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9), 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52, 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9), 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.

Background Patients with inflammatory bowel diseases (IBD) are at risk of malnutrition, which is associated with considerable disease related complications. Most available screening tools for malnutrition risk such as the malnutrition universal screening tool (MUST), do not incorporate malnutrition-promoting characteristics of IBDs. Therefore, we aimed to detect disease-specific risk factors for malnutrition development in IBD, which may be incorporated in future malnutrition screening tools. Methods A retrospective case-control study, in which detailed information regarding IBD patients treated at the IBD clinic of the Tel-Aviv Medical Center between 2010–2020 was collected. Cases were patients who developed malnutrition between clinic visits (defined as BMI≤18.5/ weight loss ≥5% of body weight during 3 months/≥10% of body weight during 6 months) and controls were those who maintained a normal nutritional status. Cases and controls were matched by age, gender, disease and disease duration. Data was collected from medical files included reported medical history, clinical manifestations of disease, disease activity, and nutritional status including MUST evaluation during clinic visits. The association between the clinical data and malnutrition development was evaluated using a logistic regression model, with adjustment for MUST components: weight loss of ≥5% of body weight and multiple (≥2) reasons for inadequate nutritional intake. Results We collected data from 118 IBD patient (cases, n=59 and controls n= 59, Crohn’s disease n=76, ulcerative colitis n=28, pouchitis patients n=14). All patients were at normal nutritional status at baseline. Patients were followed for a period of 6.2±3.0 months during which, cases lost 5.3±2.3 kg (10.4±4.8 % body weight) and controls gained 0.2±2.3 kg )0.2±3.5 % body weight) (p Conclusion Current tools for prediction of malnutrition among IBD patients are not sensitive enough. Parameters, such as increased disease activity should prompt nutritional assessment among patients to prevent mal-nutrition. The importance of these findings should be evaluated in prospective studies.

Background An accurate and non-invasive surrogate marker of inflammation is needed for managing patients after Ileal pouch-anal anastomosis (IPAA). In this study, we evaluate the performance of fecal calprotectin (FC) in patients with ulcerative colitis (UC) who underwent IPAA and were assessed with clinical, endoscopic, and histologic examination of the pouch. Methods Medical records of patients who underwent IPAA with J-pouch formation registered in a prospectively collected database at the Tel Aviv Sourasky Medical Center, Israel, were evaluated. Clinical, endoscopic, histologic, and laboratory data were extracted. Each pouch evaluation was regarded separately. Pouchitis was defined as a Pouchitis Disease Activity Score (PDAI) of ≥7 (maximum score: 18). Results One hundred and fifty-six patients underwent 296 unique pouch evaluations. Fifty-two percent of patients were male, the median age at the time of evaluation was 43 years (IQR 35–58), and the median pouch age from the closure of the ileostomy was 10 years (IQR 2.5–15). The median [IQR] FC values were significantly lower in patients without pouchitis than in patients with pouchitis (208 [96–478] vs. 550 [250–1051] ug/g, p Conclusion FC levels increase among patients with pouchitis and increase with increasing endoscopic and histologic inflammation. A FC of over 400 ug/g had good discriminative ability as a predictor of significant endoscopic disease. We suggest that in patients with symptoms of pouchitis and an FC level above 400 ug/g, antibiotic treatment can be initiated without awaiting pouchoscopy. Further research is needed to define FC concentrations more precisely among various outcome measures of interest in these patients.

Background Education of inflammatory bowel disease (IBD) patients regarding their disease, therapeutic aims and options, is important for patients’ empowerment and commitment to disease management. Currently, there is no standardized and validated tool for assessment patients’ knowledge of their disease. Therefore, we aimed to develop a questionnaire to evaluate IBD patients’ understanding of disease pathophysiology and treatment. Methods We have developed the Understanding IBD Questionnaires (U-IBDQ), consisting of multiple-choice questions in two version [for Crohn’s disease (CD) and ulcerative colitis (UC)]. U-The U-IBDQ is composed of 36 questions covering 8 IBD topics. Each question received a similar weight, and total score ranges between 0–100. Questionnaires were tested for: content validity by an independent multidisciplinary stirring committee using the content validity index, face validity, readability and responsiveness on a pilot group of IBD patients. Convergent validity was assessed by correlating scores of the U-IBDQ with physician’s subjective assessment of disease understanding and knowledge. Discriminant validity was assessed by comparison to healthy controls (HC), patients with chronic gastrointestinal (GI) conditions other than IBD, and to GI nurses. A test-retest reliability was assessed among a sub-population of IBD patients which were asked to fill-in the U-IBDQ twice. Multivariate analysis was used to determine associated factors of a high level of disease understanding. Results Study population consisted of IBD patients (n=106), HC (n=35), chronic GI disease patients (n=38) and GI nurses (n=19). Mean U-IBDQ score among IBD patients was 56.5±21.9, not differing between CD and UC patients (P=0.941). There was a strong correlation between the U-IBDQ score and the physician’s subjective score (r=0.747, P Independent factors associated with high U-IBDQ scores included academic education (OR=1.21, 95% CI 1.10–1.33, P Conclusion We have developed and meticulously validated the U-IBDQ. This is a short, self-report questionnaire that has demonstrated good reliability and validity in measuring understanding of disease pathophysiology and treatment in IBD.

Background We sought to define the effectiveness of tofacitinib in a real-world (RW) cohort of patients with moderate to severe ulcerative colitis (UC). Methods This was a multi-center retrospective observational cohort study (2017–2020). Clinical response and remission were defined as a reduction in Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) of ≥3, and SCCAI ≤2 or a PMS ≤1, respectively. Results We included 73 patients (47% male; median age 26 years [IQR 19.5–39.5], disease duration 7 years [IQR 2.5–14.5], follow-up 7.1 months [IQR 3–12]), 91% biologics-experienced, and 74% ≥ 2-biologics. Half of patients used concomitant steroids. Overall, 56.1% discontinued therapy due to either lack of response and/or adverse events (AEs), median time to discontinuation - 9.7 months (IQR 3.4–16). Based on per-protocol analysis, after induction (week-8–16), 33.3% achieved response, 23.3% remission, and 19% corticosteroid free remission. At early maintenance (week 26), 50% achieved response, 26.8% remission, and 24.4% corticosteroid free remission. There were no differences between biologics-experienced and naïve patients. Seventeen patients (23.2%) had an AE: herpes zoster- 2.7%, hospitalization- 12.3%, and colectomy- 2.7%. Remitters had higher albumin level compared with non-remitters (4.2±0.35 Vs. 3.8±0.35, P=0.023, respectively). Conclusion In this multicenter RW cohort of highly biologics - experienced patients with UC, those who continued tofacitinib throughout induction achieved 50% response and 27% remission. Tofacitinib was well-tolerated.

Background Crohn’s disease exclusion diet (CDED) with partial enteral nutrition (PEN) is effective for induction of remission in children with mild-moderate Crohn’s disease (CD). Here we evaluated CDED in adults with CD. Methods This was an open-label prospective randomized controlled pilot trial in patients with mild-moderate CD defined as Harvey-Bradshaw Index (HBI) between 5–14, active disease on colonoscopy, or imaging with calprotectin>200 μ/gr. Group-I received CDED+PEN, and Group-II CDED-alone. A colonoscopy was performed at week-24. Endoscopic remission (ER) was defined as Simple Endoscopic Score for CD (SES-CD)≤3. The primary end-point was corticosteroid (CS) free remission defined as HBI Results Forty patients were included (median age 30 years [IQR;24–39], 19 patients- Group-I, 21 patients- Group-II). By intention-to-treat (ITT) analysis CS-free remission at week-6 was 62.5% of patients (25/40), comparable between Group-I 68.4%(13/19) vs.Group-II: 57.1%(12/21) (P=.46). Among remitters at week-6, sustained remission was present in 88%(22/25) week-12, and 80%(20/25) week-24. For patients with baseline elevated C-reactive protein (CRP) (n=30), median CRP decreased from 14.5 mg/L [IQR;7.7–37] to 8.4[IQR;5.4–18.5] at week6(P=.006), and to 8[IQR;5.4–20.6] week-24(P=.002). ER at week-24 was present in 14/28 patients (50%) and was 14/40(35%) by ITT. ER week-24 was similar between groups, 8/15(53.3%) vs. 6/13(46.1%) (P=.7). A comparison between baseline and week-24 SES-CD revealed a median of 5-points decrease (IQR; [-6.25]-[-1]), corresponding to 72.8% (IQR;20–100%) decline from baseline (P=.003). Conclusion CDED with or without PEN was effective for induction and maintenance of remission in adults with mild to moderate CD and may lead to endoscopic remission.

Background Biologic treatments are inherently associated with an increased risk of infections, and recipients are intuitively considered at-risk for a more severe course of COVID-19. However, the actual risks are not fully described, neither are the appropriate adjustments needed to mitigate such risks. Methods Nation-wide registry was set up by Israeli IBD Section, to characterize course of COVID-19 in IBD patients who contacted SARS-CoV-2 infection while on biologics. We prospectively collected demographic and clinical data, and analyzed COVID-19 outcomes with regard to the specific treatments. Results Between Apr and Oct 2020, 144 patients with an established IBD diagnosis and confirmed COVID-19 were enrolled at 20 IBD referral centers. The majority of patients was under the age of 40 (113, 78%), 9 (6%) were younger than 18, only 4 patients (3%) over the age of 70. 94 patients received biologics, as monotherapy (76, 52.8%), combined with immunomodulators (9, 10%) or concomitant corticosteroids (9, 10%). 37 patients (26%) were reported with moderate and severe COVID-19 course, third of them (13) on biologics. 24 patents (17%) were admitted for hospitalization, the rest managed in home setting (114, 79%) and hotels converted into makeshift healthcare facilities (6, 4%). Fifteen patients (10%) required non-invasive ventilation and oxygen support, 3 patients (2%) went on mechanical ventilation. All patients recovered uneventfully, with no mortalities reported. Age was the most significant factor associated with moderate and severe disease. We found no correlation between bowel disease activity and the severity of COVID-19 course. The rate of serious COVID-19 for the 94 patients who had received biologics was significantly lower than that of 50 patients who were not treated with biologics (13/94 vs 24/50; RR 0.29 [95% CI, 0.161–0.515]; p < 0.0001). On adjusting for age, gender, comorbidities, IBD phenotype and activity, the surprising ameliorating effect associated with biologics was profound and significant (OR, 0.082 [95% CI 0.009-0.621], p =0.013) in all age categories. Conclusion Our results are reassuring and encouraging, and do not suggest that therapeutic immune suppression renders IBD patients particularly vulnerable for more severe course of the COVID-19. Adjusted odds for severe COVID-19 course actually decreased significantly in patients treated with biologics. It could be speculated that cytokine inhibition may mitigate progression of the infection to a devastating hyperinflammatory state. Continuing necessary maintenance immune suppression seems to be appropriate and safe approach, despite the COVID-19 pandemic.

Background Vedolizumab (VDZ) is an effective therapy in patients with Crohn’s disease (CD). Early prediction of response remains an unmet need. We aimed to evaluate whether abdominal imaging can predict response to VDZ. Methods Abdominal imaging [Computed tomography enterography (CTE) or magnetic resonance enterography (MRE)] of CD patients initiating therapy with VDZ was evaluated, up to 4 months before VDZ initiation. Response to VDZ was determined at week 26 using the Harvey–Bradshaw index (HBI) or the Crohn’s Disease Activity Index (CDAI), in cases no objective score was available it was defined based on the physician assessment. Results Thirty-three CD patients were included. At week 26, clinical response and remission were achieved in 20(60.6%) and 14(42.4%) patients, respectively. CRP and Calprotectin levels were available for 22/33 and 7/33 patients at week 26. As expected, levels trended lower in remission versus no remission- median CRP 2.41mg/L [IQR 1.3–4.5] vs 10.2[1.6–44.6], p=0.11 and 23.5 µg/g [5–42] vs 2002.8[191–2003], p=0.095, though this did not reach statistical significance. Clinical remission versus no remission was significantly associated with being biologic naïve, 8/14 vs 2/19 (p=0.01) and no prior CD surgeries, 10/14 vs 6/19 (p=0.04). Characteristics of local inflammation as mural edema, fibrofatty proliferation or lymphadenopathy were higher in patients achieving remission versus non-remission. The presence of either mural edema or fibro-fatty proliferation was significantly associated with remission (12/14 vs 9/19, p=0.03). The presence of stenosis in imaging was nominally higher in patients failing to achieve remission (14/19 vs 6/14, p=0.15). Number of diseased segments, length of inflammation or the maximal bowel thickness were similar in remission and no-remission. Conclusion Baseline imaging may help to predict remission based on the presence of either mural edema or fibrofatty proliferation and the absence of stenosis

Background The correlation between vedolizumab trough levels and inflammatory bowel diseases (IBD) remission rates has not yet been fully defined. We aimed to evaluate the association between vedolizumab serum trough levels and disease clinical and extra-intestinal manifestations (EIMs) and biomarker activity in IBD patients. Methods Forty-six patients (31 ulcerative colitis, 15 Crohn’s disease) who started vedolizumab therapy were retrospectively followed. Clinical and laboratory data were collected before treatment, during induction and maintenance until week 52 from initiation. Documentation of EIMs included peripheral and axial arthropathy, cutaneous and ocular manifestations and perianal disease. Clinical remission was defined as a Harvey-Bradshaw Index (HBI) Results Higher week-2 trough serum vedolizumab levels were associated with week 14 clinical remission compared to patients with an active disease (30.55±2.22 µg/ml vs 22.28±3.57µg/ml, p=0.05) and with weeks-14 and -30 biomarker normalization (33.77±2.98 µg/ml vs 23.6±3.19 µg/ml, p=0.05 and 30.33±1.95 µg/ml vs 19.66±6.83 µg/ml, p=0.05, respectively). Week-6 vedolizumab levels were associated with week-30 clinical remission (30.52±3.48 µg/ml vs 15.35±4.94 µg/ml, p=0.03) and biomarker normalization (28.44±2.36 µg/ml vs 15.76±4.87µg/ml, p=0.02), and week 14 vedolizumab levels were associated week 30 biomarker normalization (14.81±1.64 µg/ml vs 6.23±2.25 µg/ml, p=0.03). Throughout the follow-up period, 24% of patients presented with EIMs (n=11). No association was found between vedolizumab levels and endoscopic outcomes or EIMs activity. Conclusion Trough serum vedolizumab levels at induction is associated with remission induction and maintenance but not with EIMs improvement. Assessment of early vedolizumab trough levels may be considered for prediction of response to therapy.

BACKGROUND Biomarker normalization and endoscopic remission are superior to clinical remission in achieving improved long-term clinical outcomes in patients with inflammatory bowel diseases. GOAL To study whether higher maintenance adalimumab levels are associated with clinical remission, biomarker normalization, and endoscopic remission. STUDY Data were collected retrospectively from the patients' medical records. We defined clinical remission as a Harvey Bradshaw Index ≤5 or a partial Mayo score ≤2 for Crohn's disease (CD) and ulcerative colitis (UC), respectively, biomarker normalization as a C-reactive protein

Background Carbapenemase-producing Enterobacteriaceae (CPE) infections lead to considerable morbidity and mortality. We assessed the potential of fecal microbiota transplantation (FMT) to eradicate CPE carriage and aimed to explain failure or success through microbiome analyses. Methods In this prospective cohort study, all consenting eligible CPE carriers received oral capsulized FMT for 2 days. Primary outcome was CPE eradication at 1 month, defined by 3 consecutive negative rectal swabs, the last also negative for carbapenemase gene by polymerase chain reaction. Comprehensive metagenomics analysis of the intestinal microbiome of donors and recipients before and after FMT was performed. Results Fifteen CPE carriers received FMT, 13 of whom completed 2 days of treatment. CPE eradication at 1 month was successful in 9/15 and 9/13, respectively. Bacterial communities showed significant changes in both beta and alpha diversity metrics among participants who achieved CPE eradication that were not observed among failures. Post-FMT samples’ beta-diversity clustered according to the treatment outcome, both in taxonomy and in function. We observed a significant decrease in beta diversity in participants who received post-FMT antibiotics. Enterobacteriaceae abundance decreased in post-FMT samples of the responders but increased among failures. Functionally, a clear demarcation between responders (who were similar to the donors) and failures was shown, driven by antimicrobial resistance genes. Conclusions Our study provides the biological explanation for the effect of FMT against CPE carriage. Decolonization of CPE by FMT is likely mediated by compositional and functional shifts in the microbiome. Thus, FMT might be an efficient strategy for sustained CPE eradication. Clinical Trials Registration NCT03167398.

INTRODUCTION: Ustekinumab is an effective treatment of Crohn’s disease (CD). Real-world data addressing the efficacy and safety of ustekinumab are scarce. AIM: Our aim was to assess the safety and efficacy of ustekinumab in a large national patient cohort. METHODS: A prospective multicenter study, in which we followed patients with active CD treated with ustekinumab for 24 weeks. Induction dose was intravenous ranging from 260 to 520 mg, according to body weight, followed by 90 mg doses given subcutaneously every 8 weeks. Clinical response was defined as a reduction of at least 1 severity category, as defined by Harvey–Bradshaw index (HBI). Patients with HBI

Supplemental material, sj-pdf-1-ueg-10.1177_2050640620951400 for Vedolizumab is effective and safe in elderly inflammatory bowel disease patients: a binational, multicenter, retrospective cohort study by Nathaniel Aviv Cohen, Nikolas Plevris, Uri Kopylov, Anna Grinman, Bella Ungar, Henit Yanai, Haim Leibovitzh, Naomi Fliss Isakov, Ayal Hirsch, Einat Ritter, Yulia Ron, Ariella Bar-Gil Shitrit, Eran Goldin, Iris Dotan, Shomron Ben Horin, Charlie W Lees and Nitsan Maharshak in United European Gastroenterology Journal

Background: Bariatric surgery is often the preferred method to resolve obesity and diabetes, with ~800,000 cases worldwide yearly and high outcome variability. The ability to predict the long-term BMI change following surgery has important implications on individuals and the health care system in general. Given the tight connection between eating habits, sugar consumption, BMI and the gut microbiome, we tested whether the microbiome before any treatment is associated with different treatment outcomes, as well as other intakes (HDL, Triglycerides, etc.).Results: A projection of the gut microbiome composition of obese (sampled before and after bariatric surgery) and slim patients into principal components was performed and the relation between this projection and surgery outcome was studied. The projection reveals 3 different microbiome profiles belonging to slim, obese and obese who underwent bariatric surgery, with post-surgery more different from the slim than the obese. The same projection allows for a prediction of BMI loss following bariatric surgery, using only the pre-surgery microbiome. A different projection is associated with sugar metabolism and A1C levels. Conclusions: - the gut microbiome can be naturally decomposed into main components depicting the patient's development and predicting in advance the outcome. Those may be translated into a better clinical management of obese individuals planning to undergo metabolic surgery.