Faecal levels of zonula occludens toxin in paediatric patients with Crohn’s disease and their association with the intestinal microbiota

AbstractIntestinal dysbiosis is key in the onset and development of Crohn’s disease (CD). We evaluated the microbiota changes in CD patients before and after a six-month anti-TNF treatment, comparing these changes with the microbiota of healthy subjects. This prospective multicenter observational study involved 27 CD patients initiating anti-TNF treatment and 16 healthy individuals. Inflammatory activity was determined at baseline, 3 and 6 months, classifying patients into responders and non-responders. Fecal microbiota was analyzed by massive genomic sequencing thought 16S rRNA amplicon sequencing before and after six months of anti-TNF treatment. The CD cohort showed a decrease in genera of the class Clostridia, short-chain fatty acid producers, and an increase in the phylum Proteobacteria (p < 0.01) versus the healthy cohort. After anti-TNF treatment, the phylum Proteobacteria also increased in non-responders versus responders (13/27) (p < 0.005), with the class Clostridia increasing. In addition, alpha diversity increased in responders versus non-responders (p < 0.01), tending towards eubiosis. An association was found (p < 0.001) in the F.prausnitzii/E.coli ratio between responders and non-responders. The F/E ratio was the most accurate biomarker of anti-TNF response (area under the curve 0.87). Thus, anti-TNF treatment allows partial restoration of intestinal microbiota in responders and the F.prausnitzii/E.coli ratio can provide a reliable indicator of response to anti-TNF in CD.

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P426 Long-term safety of adalimumab in paediatric patients with Crohn's disease

Journal of Crohn s and Colitis ◽

10.1016/s1873-9946(14)60546-8 ◽

2014 ◽

Vol 8 ◽

pp. S243-S244

Author(s):

J. Rosh ◽

F. Ruemmele ◽

M. Dubinsky ◽

J. Escher ◽

J. Kierkus ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Paediatric Patients

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Differences in the location and activity of intestinal Crohn’s disease lesions between adult and paediatric patients detected with MRI

European Radiology ◽

10.1007/s00330-012-2482-6 ◽

2012 ◽

Vol 22 (11) ◽

pp. 2465-2477 ◽

Cited By ~ 20

Author(s):

Francesca Maccioni ◽

Franca Viola ◽

Federica Carrozzo ◽

Giovanni Di Nardo ◽

Anna Rosaria Pino ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Paediatric Patients

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Fecal microbiota Profiling in Irritable Bowel Syndrome and Inflammatory Bowel Disease Patients with Irritable Bowel Syndrome-Type Symptoms

10.21203/rs.3.rs-152044/v1 ◽

2021 ◽

Author(s):

Xiufang Cui ◽

Haiyang Wang ◽

Ziping Ye ◽

Yi Li ◽

Xinyun Qiu ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Irritable Bowel Syndrome ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Intestinal Microbiota ◽

Bowel Disease ◽

Sectional Study ◽

Genus Level ◽

Inflammatory Bowel ◽

Irritable Bowel

Abstract BACKGROUND: The intestinal microbiota is thought to be involved in the occurrence of Inflammatory Bowel Disease in remission (IBDR) with Irritable Bowel Syndrome (IBS)-type symptoms, but the specific distinct profile of these bacteria remains unclear. Therefore, the purpose of this research is to investigate this issue by conducting a cross-sectional study.METHODS: IBS patients were diagnosed according to Rome Ⅳ criteria, IBD diagnosed according to the criteria of European Crohn & Colitis Organization (ECCO), IBDR patients with IBS-type symptoms were defined according to related IBS-type symptoms meeting the Rome IV criteria in IBDR patients, and were included Crohn’s disease in remission (CDR) and ulcerative colitis in remission (UCR) based on Crohn’s Disease Activity Index (DAI) and Mayo Scoring System respectively. Healthy controls come from the physical examination center and exclude people with underlying diseases. All enrolled subjects were divided into six groups, as followed: Health Control, IBS, CDR with IBS-type symptoms (CDR-IBS+), CDR without IBS-type symptoms (CDR-IBS-), UCR-IBS+ and UCR-IBS-. We collected fresh fecal samples from all subjects and applied 16S rRNA sequencing analysis to detect the structure and diversity of the microbiota among different groups. RESULTS: A total of 97 subjects were included in this study, of which 18 were health controls, 34 IBS patients, 25 CDR and 20 UCR. The richness of intestinal microbiota in CDR-IBS-was significantly lower than that in the control and IBS groups based on the analysis of observed species and Chao index (P<0.05). The observed species index in CDR-IBS+ was significantly higher than CDR-IBS- group (median index: 254.8 vs 203, P=0.036). No difference was found in Alpha diversity between UCR-IBS+ and UCR-IBS-. At phylum level, there was no significant difference between UC or CD with IBS-type symptoms and those without related symptoms. At genus level, the number of Faecalibacterium in CDR-IBS+ increased significantly while Fusobacterium decreased compared with CDR-IBS-(mean relative abundance of Faecalibacterium: 20.35% vs 5.18%, P<0.05; Fusobacterium: 1.51% vs 5.2%, P<0.05). However, compared with UCR-IBS - group, the number of Faecalibacterium in UCR-IBS+ group decreased, while the number of Streptococcus increased, but there was no statistical difference in the genus structure. Regardless of the phylum or genus level, the abundance and composition of the microbiota of IBS patients were not distinct from those of healthy people.CONCLUSIONS: CD patients in remission with IBS-type symptoms may be related to the increase of Faecalibacterium and decrease of Fusobacterium. UC patients in remission with IBS-type symptoms cannot be explained by changes in the abundance and structure of intestinal microbiota from our across-sectional study.

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Partial enteral nutrition has no benefit on bone health but improves growth in paediatric patients with quiescent or mild Crohn's disease

Clinical Nutrition ◽

10.1016/j.clnu.2020.04.012 ◽

2020 ◽

Vol 39 (12) ◽

pp. 3786-3796 ◽

Cited By ~ 1

Author(s):

Annecarin Brückner ◽

Katharina Julia Werkstetter ◽

Klara Frivolt ◽

Engy Shokry ◽

Mohamed Ahmed ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Enteral Nutrition ◽

Bone Health ◽

Paediatric Patients

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Sa1900 BIOMARKERS RESPONSE TO ANTI-TNF TREATMENT IN CROHN'S DISEASE THROUGH THE INTESTINAL MICROBIOTA

Gastroenterology ◽

10.1016/s0016-5085(20)31859-x ◽

2020 ◽

Vol 158 (6) ◽

pp. S-471

Author(s):

Laura Sanchis ◽

Sergio Manresa-Vera ◽

Juan F. Martínez ◽

Marina Valls Gandia ◽

Marisa Iborra ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Intestinal Microbiota

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DOP71 Efficacy, safety, and tolerability of ustekinumab in paediatric patients with moderately to severely active Crohn’s disease: Results from, UniStar, a phase 1 study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.110 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S107-S108

Author(s):

J Rosh ◽

D Turner ◽

A Griffiths ◽

D Jacobstein ◽

O Adedokun ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Opportunistic Infections ◽

Activity Index ◽

Phase 1 ◽

Double Blind ◽

Faecal Calprotectin ◽

Adequate Treatment ◽

Safety And Efficacy ◽

Paediatric Patients

Abstract Background Ustekinumab (UST) is approved for the treatment of adults with moderate to severe Crohn’s disease (CD). The objective of this study was to evaluate the pharmacokinetics (PK), safety, and efficacy of UST in paediatric patients with moderately to severely active CD who had failed treatment with corticosteroids (CS) and/or immunomodulators (IM) and/or anti-tumour necrosis factor (TNF) therapies. Here, we report the safety and efficacy results through Week 16; PK results are reported separately. Methods This was a Phase 1, multicentre, 16-week, double-blind induction dose-ranging study (NCT02968108) in patients aged 2 to <18 years (body weight [BW] ≥10 kg) with a Paediatric CD Activity Index (PCDAI) score >30 and at least an abnormal C-reactive protein >3.0 mg/l or faecal calprotectin >250 µg/g), or ulcerations in the ileum or colon upon ileocolonoscopy despite adequate treatment with CS ± IM ± anti-TNF therapy. Patients were randomised (1:1) and stratified by weight and prior anti-TNF use for induction to one of 2 weight range-based intravenous (IV) doses: 130mg vs. 390 mg if BW ≥40 kg and 3 mg/kg vs. 9 mg/kg if BW <40 kg. At week 8, all patients received a single subcutaneous (SC) UST maintenance dose of 90mg if BW ≥40 kg or 2 mg/kg if BW <40 kg. Results Forty-four patients (59% ≥40kg BW; >90% anti-TNF exposed) were randomised (n = 23 lower dose; n = 21 higher dose) and treated with UST. Baseline characteristics are summarised in Table 1. At week 16, in the lower dose and higher dose groups, 52%/52% achieved clinical response (reduction in PCDAI ≥15) and 22%/29% had clinical remission (PCDAI ≤10), respectively (Table 2). In addition, 32% and 28% of patients showed endoscopic response (reduction in Simple Endoscopic Score for CD of ≥50%), respectively. Through week 16, 73% of patients reported ≥1 adverse event (AE; 82.6% lower dose vs. 62% higher dose); 2 discontinued due to AEs (1 in each group). Serious AEs occurred in 16% of patients (26% lower dose and 5% higher dose, with CD exacerbation being the most frequent (13%/5%, respectively). Infections occurred in 41% of patients (1 was serious, which was intestinal abscess that spontaneously resolved with sequelae). No injection site reactions, opportunistic infections, malignancies, or deaths were reported. No antibodies to UST were observed. Conclusion As early as 3 weeks and through 16 weeks, both the lower and higher doses of UST (IV week 0 and SC at week 8) improved clinical and endoscopic disease activity in this previously treatment-refractory group of children with CD. The safety profile was consistent with that for UST in adults with CD.

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