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Background Inflammatory bowel diseases (IBD, Crohn’s disease [CD], ulcerative colitis [UC]) are chronic immune-mediated systemic diseases with unknown aetiology. In the past few years, experimental studies revealed associations of human serum and plasma metabolites’ with IBD with a possible discriminative power between IBD and healthy subjects. Our study focused on the utility of plasma metabolome profiling as a diagnostic marker in patients with different phenotypes. Methods IBD patients were enrolled in a double-centre prospective cohort study. Large number of healthy subjects were included to reduce methodological bias. Blood samples were obtained at baseline and stored at –20°C and plasma metabolites were measured by high performance liquid chromatography coupled with tandem-mass spectrometry (HPLC-MS/MS). Logistic regression, minimum redundancy maximal relevance (mRMR), principal component analysis (PCA), and linear discriminant analysis (LDA) were used to calculate discriminative power. Results Plasma metabolome profile of 26 IBD (13 UC and 12 CD) patients and 168 HC participants were analyzed, and 388 metabolites were measured. 33 and 58% of CD patients and 31 and 39% of UC patients had clinical and endoscopic activity based on clinical (mean pMayo: 2.8±3.4, CDAI: 56±62) and endoscopic (mean PanMayo: 7.4±13.3 and SES-CD: 7.3±8.2) indices. Low plasma level of cysteine (CV=-0.36; p Conclusion Based on our results, plasma metabolite levels may help to discriminate IBD and healthy subjects. Integrative analysis of different biological samples may potentially predict IBD and could promote achieving personalized medicine. Further sample collections and analysis within this study can reveal discriminative metabolite fingerprints among IBD subtypes and correlations with activity as well.

Background The SARS-CoV-2 pandemic has raised issues in the management of inflammatory bowel diseases (IBD). This study aimed to assess the efficacy of different anti-SARS-CoV-2 vaccines under different treatments in IBD patients and identify predictive factors associated with lower serological response, including anti-TNF drug levels. Methods A prospective, multicentre study of IBD patients was conducted following mRNA and non-mRNA anti-SARS-CoV-2 vaccination. Healthy control (HC) patients were enrolled to reduce bias. Baseline and week 14 samples were obtained following the second dose to assess the impact of conventional and biological treatments. Clinical and biochemical activity, serological response level, and anti-TNF drug levels were measured. Results This study included 199 IBD (Table 1.; mean age, 40.9 ± 12.72 years) and 77 HC participants. Most patients (76.9%) and all HCs received mRNA vaccines. Half of the IBD patients were on biological treatment (Table 2.; anti-TNF 68.7%). Combined immunomodulation and biological treatment were associated with lower serological response (Figure 1.; p0.05). Vaccination had no impact on disease activity. Conclusion Anti-SARS-CoV-2 vaccination is considerably efficacious in IBD patients, with mRNA vaccines promoting better antibody levels. The negative impact of combined biological treatment, especially with high adalimumab drug levels, on serological response to vaccination should be considered. Although mid-term durability of vaccination is encouraging, more data are needed to expand existing understanding on this issue.

Background Ulcerative colitis (UC) is a systemic immune-mediated disease that affects the colon continuously. Colonoscopy plays a crucial role in management of UC that helps to assess mucosal healing objectively along the colon. Different scoring systems are available to assess severity, however most of them does not take into consideration of disease extent. Extension modified (PanMayo) Mayo endoscopic subscore (MES) system has been shown to correlate with UCEIS and Riley scores and calprotectin. Our study aimed to assess the predictive power and accuracy of PanMayo score compared to MES, UCEIS and Dublin to predict mid- and long-term disease outcomes. Methods This is retrospective, two-center study. UC patients, who underwent colonoscopy due to any reason between 2016 and 2018, were consecutively enrolled. PanMayo, MES, UCEIS and Dublin scores and additionally the Nancy histology score (where available) were recorded with clinical and demographical data at baseline. Disease flare, need for change in therapy (incl. initiation of biologicals, need for systemic steroids), hospitalisations and colectomy were tracked amongst patients with clinical remission (pMayo Results A total of 250 UC patients (male ratio: 0.45, median age 45 (IQR) 22.3 years) were enrolled with 156 (male ratio 0.49; mean age 46 IQR 20.8 years, Table 1.) of UC patients having baseline clinical remission. PanMayo, MES, and Dublin scores were positively associated with risk of disease flare (Figure 1.; p=0.002, p Conclusion Our study suggests that combined endoscopic assessment of the extent and severity may be more accurate in predicting disease outcomes in UC in clinical remission. PanMayo scores may be an alternative of the existing scoring system and was associated more granularly with disease outcomes. In addition, outcomes were different in patients with initial MES 0 and 1 scores.

Background Iron deficiency (ID) is often a neglected condition in inflammatory bowel disease (IBD), even though it is one of the most common extraintestinal manifestation. Our questions were the follows: If iron deficiency is part of the T2T management as CRP or fecal calprotectin and requires optimisation of the current therapy, how does this affect the medium-term outcome of the disease and the effectiveness of IV iron replacement? If the disease is active, does optimisation of therapy is sufficient to manage iron deficiency or iv. iron supplementation is also necessary? Methods Patients with ID defined by the ECCO guideline (Figure 1.) were randomly included in our prospective one-center, four arms study. Patients were divided into an active (A) and a remission (R) group. Activity was defined by CRP ≥10 mg/l or clinical activity scores CDAI ≥150, pMayo ≥3. Therapy optimisation was performed in the active group, further randomisation was performed into two subgroups: therapy modification alone (A1) or modification with iv. ferric-carboxymaltose (A2). All patients received iron supplementation in the remission group with (R2 – iron T2T group) or without therapy optimisation (R2). Every two months laboratory parameters and clinical activities were assessed until 6 months. Results 65 patients were included (CD 83.4%). Average follow-up was 3.9 months. Number of patients per group: A1:17, A2:23, R1:16, R2:9. Based on our results, iv. iron supplementation with modification in treatment was more efficient, than therapy optimisation alone, as the difference in increase in haemoglobin (p Conclusion Our results suggest, that therapy optimisation in addition to iron replacement is more effective in patients with remission and therefore biomarkers of IDA should be involved in the thight monitoring algorhytm to react T2T. However, therapy optimisation has to be associated with iv iron replacement in IBD with IDA and activity without the risk of worsening disease activity. Based on our results, ferric-carboximaltose is an effective and safe therapeutic method in the treatment of IDA associated with active or inactive IBD.

Background Iron deficiency (ID) is one of the most common extraintestinal manifestation of inflammatory bowel disease, which often remains untreated, despite the fact, that ID significantly impairs patients’ quality of life. Since anaemia develops through several pathomechanisms (e.g., occult bleeding, chronic inflammation, medicines), treating anaemia requires to manage the underlying pathological changes as well. Methods In our prospective, two-centers study, we assessed the frequency of ID among our IBD patients. The diagnosis of iron deficiency (iron deficiency anaemia [IDA], anaemia of chronic inflammation [CDA], anaemia of mixed origin [AMO]) was based on the ECCO’s anaemia guideline. According to the guideline, haemoglobin, CRP, ferritin, transferrin saturation, serum iron values, total iron binding capacity, hematocrit, and platelet counts were collected from our patients on a one-off basis. We aimed to compare the frequency of ID in a biologic centre, and in a non-biologic centre hospital as well. In addition, we assessed the frequency of the need for oral and intravenous iron replacement, respectively, based on the guideline as well. Results 720 patients were included in our study (CD 58.8%, UC 41.2 %). Average age was 43.3 years. We found, that 26.6% of our patients had anemia. There was no significant difference in the prevalence of ID (p=0.65) between CD and UC patients. Based on the ECCO criteria, 61.8% of them have ID (33.0% IDA, 23.0% AMO, 5.8% CDA), and in the rest of the cases (38.2%) it was classified to be anaemia of other origin (AOO), however, in 68.5% of these cases ID can be suspected at some degree, as ferritin was < 100 mg/l and/or transferrin saturation ≤ 20%. In total, 133 patients (69.6%) had anaemia in remission, and 58 patients (30.4%) in case of activity (CRP ≥10 mg/l). In addition, we found an association between elevated CRP levels and the prevalence/severity of anemia (p120–130 g/l) already after 2 months in 76.5% of the cases. Conclusion Based on our results, anemia and iron deficiency are common complications of IBD and correlate well with disease activity. Consequently, we suggest, that iron deficiency should be a part of the treat to target approach, and in case of ID, iv. ferric-carboximaltose is efficient in activity as well.

Background Bowel preparation prior to colonoscopy is a routine procedure and supposed to be safe. However, the exacerbation of the complaints could be observed in numerous cases after colonoscopy in patients with inflammatory bowel disease (IBD, Crohn’s disease CD, ulcerative colitis UC). Therefore, our study aimed to investigate the short- and long-term changes of the fecal microbiota composition influenced by the bowel preparation with sodium-picosulphate and magnesium-oxide. Methods IBD patients (inactive or mild) preparing for colonoscopy with bowel preparation were enrolled in the study. Control group (HC) consisted of non-IBD patients who were recommended to undergo colonoscopy due to abdominal complaints. Clinical data, blood and stool samples were collected before colonoscopy (point A), 3 days later (point B) and 4 weeks later (point C) to assess disease activity and the changes of the gut microbiome. Fecal microbiota structure was determined by sequencing V4 region of the 16S rRNA gene. Microbiome structure was determined at family level. Statistical analysis included differential abundance analysis and Mann-Whitney test, values of p Results 41 patients (9 CD, 13 UC, 19 HC) were enrolled in our study. After the bowel preparation, alpha diversity in the CD group was lower compared to UC(p=0.01) and control(p=0.02) patients at point B. Alpha diversity of UC patients was significantly higher than CD (p‹0.01) and control (p=0.03) groups at point C. Alpha diversity of UC patients increased from point A to C (p=0.04). However, a decreasing tendency in alpha diversity was observed in patients with CD at A to C period (p=0.26). These changes couldn’t be observed in the control group. Beta diversity showed slight differences between the IBD groups and the control group. After bowel preparation, beta diversity of CD patients immediately (from A to B) changed p=0.03), while beta diversity of UC patients seems to continually change from point A to C(p=0.03). Based on the differential abundance analysis, Clostridiales and Pseudomonadaceae families increased, while Bifidobacteriaceae, Carnobacteriaceae, Veillonellaceae and Pasteurellaceae families decreased in CD patients compared to the HC at point B. The most growing families in HC group were Brucellaceae, Moraxellaceae and Alcaligenaceae at A to B period. Conclusion Our findings may suggest that bowel preparation can result in a significant change in faecal microbial composition in IBD. Microbial alterations recovering earlier in UC patients due to changed mucosa. Reduced alpha diversity and altered abundance in CD may have potential role in disease exacerbation. Further examinations are needed to clarify our pilot results.

Background Changes in microbiome of the gut and decreased diversity in inflammatory bowel disease(IBD) is the subject of intense researches. The exact pathophysiological connection is lacking, but the systemic inflammation due to the microbial alterations are assumed. This study aimed to perform analysis of faecal microbiota composition simultaneously with body composition by bioelectrical impedance and nutrition habits in Crohn’s disease(CD) patients to find specific microbiota profiles connected with obesity, mesenterial fat, signs of systemic inflammation, nutritional and body composition characteristics. Methods In our prospective cohort study, CD patients were enrolled. At the inclusion, demographic and clinical data, blood, and faecal samples were obtained. Clinical disease activity was assessed by CDAI, and SES-CD. Laboratory tests were made including C-reactive protein(CRP), albumin and lipids (triglyceride, cholesterol). Faecal bacterial composition was assessed using shotgun metagenomics sequencing technique. Each patient underwent a body composition analysis via bioelectrical impedance analysis. A nutritional questionnaire was filled by each subject. Results Data of 27 CD patients with different localisation was analysed in this study (mean age was 35±11 years). According to the gut inflammation, some Blautia species correlated positively with SES-CD (p=0,004), and correlated with faecal calprotectin negatively (p=0,02), while Roseburia hominis negatively with CDAI scores(p=0,01). High CDAI scores were also associated with dysbiosis. Adlercreutzia equolifaciens and Blautia hansenii associated with triglyceride(negatively p=0,04, positively p=0,05). Firmicutes has a lower, while Bacteroidetes has a higher abundance at high cholesterol level(p=0,001, p=0,023). Lower Adlercreutzia and Lactobacillus abundance were seen in patients with high visceral fat area(p=0,05, p=0,01), while Clostridia correlated with percent body fat(p=0,025).Bifidobacterium bifidum were associated in people with low body weight or low skeletal muscle mass(p=0,01, p=0,03). Beside Clostridia, Eubacteriales also correlated with waist-hip ratio(p=0,04, p=0,04). Conclusion To our knowledge this is the first study to analyse microbiota profiles by shotgun sequencing technique in CD patients depending on body composition via bioelectrical impedance and nutrition. Changes in Blautia, Lactobacillus, Adlercreutzia, Roseburia and Bifidobacterium abundances in patients with CD and obesity highlight the importance of correlations between lipid metabolism, adipose tissue mass, and chronic inflammation. Through this, it helps to develop new therapeutic approaches, such as personalized pre- or probiotics or faecal microbiota transplantation.

Background Anti-tumor necrosis factor alpha treatments are effective and safe as first line therapy, however, their long-term efficacy is limited by primary (PNR) and secondary non-response (LOR) resulting in treatment discontinuation in approximately, 40–50% of cases. Vedolizumab (VDZ) and ustekinumab (UST) therapy could be good alternative in patient with anti-TNF failure, however, no direct comparison has been made. This study aimed to assess treatment persistence and long-term efficacy of VDZ and UST as second- and third line biological therapies in Crohn’s disease (CD) patients refractory to anti-TNF therapy. Methods In this multicentre study, CD patients on VDZ or UST maintenance therapy were enrolled. We analysed data of medical history retrospectively in case of both agents. Demographic and clinical data at baseline and one-year were obtained. Clinical (CDAI Results 200 UST and, 96 VDZ-treated patients were included in the study. After exclusion of confounders, 162 UST and, 77 VDZ-treated patients were completed the follow-up. Mean age was, 41,1 (±16,5) and, 37,9 (±11,3) years at both agents at baseline. Steroid-free clinical and biochemical remission rates did not differ between VDZ and UST groups at one year (73% vs, 73% and, 67% vs., 51%). Kaplan-Meyer analysis revealed superiority of UST during follow up (86,5% vs., 62,9%, p Conclusion We confirmed that VDZ and UST are effective and safe alternatives to CD patients who have failed to anti-TNF therapy. UST has a superiority in drug persistence compared to VDZ. Second compared to third line of sequential therapy results in better outcome in drug persistence in case of both agents, however, head-to-head comparison of both agents are needed to verify our data.

Background Inflammatory bowel disease potentially elevates the risk of infections, furthermore, disease activity and medical treatment(s) can increase the risk as well. However, both international data and recent studies do not confirm these preliminary conceptions regarding the SARS-CoV-2 infection. In addition, a number of studies have reported that less antibodies are produced against the virus in IBD patients. In January, 2021, the vaccination campaign has begun in Hungary as well, however, questions have been raised about the effectiveness and safety of the vaccine. Methods In this multicentre study, we assessed the prevalence and risk factors of COVID-19 infection, the willingness to receive COVID-19 vaccine and the efficacy of vaccination among IBD patients receiving biological therapy, based on a cross-sectional questionnaire-based study. To assess safety and antibody response to COVID-19 vaccines, we conducted a prospective study in the same Hungarian IBD centers. IgG antibody was quantified to SARS-CoV-2 spike protein and nucleocapsid, 1 week before and after the first vaccine and, 4 and, 8 weeks after the second vaccinane, respectively. Results 472 patients were enrolled in the first part of our study. SARS-CoV-2 infection was confirmed in, 16.9% of patients. Wearing gloves and masks were found to be effective in preventing infection (p=0.02; p=0.005), avoidance of communal areas had no effect on infection rates. Male sex increased the risk (p=0.008) of viral infection. Based on subjective complaints, UC patients had a worse disease course (p=0.002). Biological therapies did not increase the risk of infections. Patients vaccinated with mRNA vaccine had a significantly higher spike protein antibody titer one month after the second vaccination (p=0.004) compared to other vaccine types (Sinopharm©, Sputnik V©, Astra Zeneca©). Seropositivity was detected in, 98% of patients. Sinopharm© vaccination triggered the lowest number of side effect (p Conclusion Face mask was the most effective preventive tool. The risk of infection was not increased by biological therapy, therefore therapy discontinuation is not justified. Almost every vaccinated patient developed seropositivity two month after vaccination independently from the type of the vaccine, however, spike protein antibody was significantly higher following mRNA vaccinations.