scholarly journals Changes in the Intestinal Microbiota Are Seen Following Treatment with Infliximab in Children with Crohn’s Disease

2020 ◽  
Vol 9 (3) ◽  
pp. 687 ◽  
Author(s):  
Kinga Kowalska-Duplaga ◽  
Przemysław Kapusta ◽  
Tomasz Gosiewski ◽  
Agnieszka Sroka-Oleksiak ◽  
Agnieszka H. Ludwig-Słomczyńska ◽  
...  

The aim of the study was to determine the impact of biological treatment with tumor necrosis factor α antibodies (anti-TNF-α) on the intestinal microbiome of children with severe Crohn’s disease (CD) and to evaluate the differences in the intestinal microbiome between patients treated with biological therapy and healthy children. Microbiota composition was analyzed by 16S next-generation sequencing (NGS) and microbial profiles were compared between studied groups. Fifty-four samples (from 18 patients before and after anti-TNF-α induction therapy and 18 healthy children) were used in the sequencing analysis. Shannon’s diversity index (p = 0.003, adj. p = 0.010) and observed operational taxonomic units (OTUs) (p = 0.007, adj. p = 0.015) were different between controls and patients with prior therapy for CD. Statistically significant dissimilarities between beta diversity metrics, indicating distinct community composition across groups, were observed in patients with CD before and after therapy. We did not observe any differences between controls and patients with CD after therapy. Core microbiome analysis at species level showed that 32 species were present only in patients with CD but not in controls. The results show that biological treatment is associated with changes in the intestinal microbiome of patients with CD: these changes result in an intestinal microbiome pattern similar to that seen in healthy children. Long-term observation is necessary to determine whether treatment can lead to full restoration of a healthy-like microbiome.

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3749
Author(s):  
David L. Suskind ◽  
Dale Lee ◽  
Young-Mo Kim ◽  
Ghassan Wahbeh ◽  
Namita Singh ◽  
...  

Background: Crohn’s disease (CD) is a chronic inflammatory intestinal disorder associated with intestinal dysbiosis. Diet modulates the intestinal microbiome and therefore has a therapeutic potential. The aim of this study is to determine the potential efficacy of three versions of the specific carbohydrate diet (SCD) in active Crohn’s Disease. Methods: 18 patients with mild/moderate CD (PCDAI 15–45) aged 7 to 18 years were enrolled. Patients were randomized to either SCD, modified SCD(MSCD) or whole foods (WF) diet. Patients were evaluated at baseline, 2, 4, 8 and 12 weeks. PCDAI, inflammatory labs and multi-omics evaluations were assessed. Results: Mean age was 14.3 ± 2.9 years. At week 12, all participants (n = 10) who completed the study achieved clinical remission. The C-reactive protein decreased from 1.3 ± 0.7 at enrollment to 0.9 ± 0.5 at 12 weeks in the SCD group. In the MSCD group, the CRP decreased from 1.6 ± 1.1 at enrollment to 0.7 ± 0.1 at 12 weeks. In the WF group, the CRP decreased from 3.9 ± 4.3 at enrollment to 1.6 ± 1.3 at 12 weeks. In addition, the microbiome composition shifted in all patients across the study period. While the nature of the changes was largely patient specific, the predicted metabolic mode of the organisms increasing and decreasing in activity was consistent across patients. Conclusions: This study emphasizes the impact of diet in CD. Each diet had a positive effect on symptoms and inflammatory burden; the more exclusionary diets were associated with a better resolution of inflammation.


2019 ◽  
Vol 30 (01) ◽  
pp. 027-032
Author(s):  
Vojtech Dotlacil ◽  
Jiri Bronsky ◽  
Ondrej Hradsky ◽  
Barbora Frybova ◽  
Stepan Coufal ◽  
...  

Abstract Introduction The incidence of Crohn's disease (CD) within the pediatric population is increasing worldwide. Despite a growing number of these patients receiving anti-tumor necrosis factor α therapy (anti-TNF-α), one-third of them still require surgery. There is limited data as to whether anti-TNF-α influences postoperative complications. We evaluated postoperative complications in patients who were or were not exposed to anti-TNF-α therapy in our institutional cohort. Materials and Methods A retrospective review of CD patients who underwent abdominal surgery between September 2013 and September 2018 was performed. The patients were divided into two groups based on whether they were treated with anti-TNF-α within 90 days before surgery. Thirty-day postoperative complications were assessed using Clavien–Dindo classification (D-C); this examination included surgical site infections (SSIs), stoma complications, intra-abdominal septic complications, non-SSIs, bleeding, ileus, readmission rate, and return to the operating room. Mann–Whitney U-test, Fisher's exact test, and multivariate logistic regression analyses were used for statistical analysis. Results Sixty-five patients (41 males) with a median age of 16 years (range: 7–19) at the time of operation were identified. The most common surgery was ileocecal resection in 49 (75%) patients. Forty-three (66.2%) patients were treated with anti-TNF-α preoperatively. Seven patients (11%) experienced postoperative complications. There was no statistically significant difference in postoperative complication in patients who did or did not receive anti-TNF-α before surgery (D-C minor 2.3% vs. 4.6%, p = 1; D-C major 7% vs. 9.1%, p = 1). Conclusion The use of anti-TNF-α in pediatric CD patients within the 90 days prior to their abdominal surgery was not associated with an increased risk of 30-day postoperative complications.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kinga Kowalska-Duplaga ◽  
Tomasz Gosiewski ◽  
Przemysław Kapusta ◽  
Agnieszka Sroka-Oleksiak ◽  
Andrzej Wędrychowicz ◽  
...  

AbstractThe aetiology of inflammatory bowel diseases (IBD) seems to be strongly connected to changes in the enteral microbiome. The dysbiosis pattern seen in Crohn’s disease (CD) differs among published studies depending on patients’ age, disease phenotype and microbiome research methods. The aims was to investigate microbiome in treatment-naive paediatric patients to get an insight into its structure at the early stage of the disease in comparison to healthy. Stool samples were obtained from controls and newly diagnosed patients prior to any intervention. Microbiota was analysed by 16SrRNAnext-generation-sequencing (NGS). Differences in the within-sample phylotype richness and evenness (alpha diversity) were detected between controls and patients. Statistically significant dissimilarities between samples were present for all used metrics. We also found a significant increase in the abundance of OTUs of the Enterococcus genus and reduction in, among others, Bifidobacterium (B. adolescentis), Roseburia (R.faecis), Faecalibacterium (F. prausnitzii), Gemmiger (G. formicilis), Ruminococcus (R. bromii) and Veillonellaceae (Dialister). Moreover, differences in alpha and beta diversities in respect to calprotectin and PCDAI were observed: patients with calprotectin <100 µg/g and with PCDAI below 10 points vs those with calprotectin >100 µg/g and mild (10–27.7 points), moderate (27.5–40 points) or severe (>40 points) CD disease activity had higher richness and diversity of gut microbiota. The results of our study highlight reduced diversity and dysbiosis at the earliest stage of the disease. Microbial imbalance and low abundance of butyrate-producing bacteria, including Bifidobacterium adolescentis, may suggest benefits of microbial modification therapy.


2021 ◽  
Vol 09 (07) ◽  
pp. E1136-E1144
Author(s):  
Astrid de Maissin ◽  
Remi Vallée ◽  
Mathurin Flamant ◽  
Marie Fondain-Bossiere ◽  
Catherine Le Berre ◽  
...  

Abstract Background and study aims Computer-aided diagnostic tools using deep neural networks are efficient for detection of lesions in endoscopy but require a huge number of images. The impact of the quality of annotation has not been tested yet. Here we describe a multi-expert annotated dataset of images extracted from capsules from Crohn’s disease patients and the impact of the quality of annotations on the accuracy of a recurrent attention neural network. Methods Images of capsule were annotated by a reader first and then reviewed by three experts in inflammatory bowel disease. Concordance analysis between experts was evaluated by Fleiss’ kappa and all the discordant images were, again, read by all the endoscopists to obtain a consensus annotation. A recurrent attention neural network developed for the study was tested before and after the consensus annotation. Available neural networks (ResNet and VGGNet) were also tested under the same conditions. Results The final dataset included 3498 images with 2124 non-pathological (60.7 %), 1360 pathological (38.9 %), and 14 (0.4 %) inconclusive. Agreement of the experts was good for distinguishing pathological and non-pathological images with a kappa of 0.79 (P < 0.0001). The accuracy of our classifier and the available neural networks increased after the consensus annotation with a precision of 93.7 %, sensitivity of 93 %, and specificity of 95 %. Conclusions The accuracy of the neural network increased with improved annotations, suggesting that the number of images needed for the development of these systems could be diminished using a well-designed dataset.


2018 ◽  
Vol 37 ◽  
pp. S234
Author(s):  
M. Hilligsøe ◽  
N.D. Eriksen ◽  
M.H. Jacobsen ◽  
L.H. Kaagaard ◽  
L. Vinter-Jensen ◽  
...  

2001 ◽  
Vol 120 (5) ◽  
pp. A273-A273
Author(s):  
C SERRA ◽  
P GIONCHETTI ◽  
L VOLPE ◽  
C MORELLI ◽  
M CAMPIERI ◽  
...  

Author(s):  
Neeraj Narula ◽  
Emily C L Wong ◽  
Parambir S Dulai ◽  
John K Marshall ◽  
Jean-Frederic Colombel ◽  
...  

Abstract Background and Aims There is paucity of evidence on the reversibility of Crohn’s disease [CD]-related strictures treated with therapies. We aimed to describe the clinical and endoscopic outcomes of CD patients with non-passable strictures. Methods This was a post-hoc analysis of three large CD clinical trial programmes examining outcomes with infliximab, ustekinumab, and azathioprine, which included data on 576 patients including 105 with non-passable strictures and 45 with passable strictures, as measured using the Simple Endoscopic Score for Crohn’s Disease [SES-CD]. The impact of non-passable strictures on achieving clinical remission [CR] and endoscopic remission [ER] was assessed using multivariate logistic regression models. CR was defined as a Crohn’s Disease Activity Index [CDAI] &lt;150, clinical response as a CDAI reduction of ≥100 points, and ER as SES-CD score &lt;3. Results After 1 year of treatment, patients with non-passable strictures demonstrated the ability to achieve passable or no strictures in 62.5% of cases, with 52.4% and 37.5% attaining CR and ER, respectively. However, patients with non-passable strictures at baseline were less likely to demonstrate symptom improvement compared with those with passable or no strictures, with reduced odds of 1-year CR (adjusted odds ratio [aOR] 0.17, 95% CI 0.03–0.99, p = 0.048). No significant differences were observed between patients with non-passable strictures at baseline and those with passable or no strictures in rates of ER [aOR 0.82, 95% CI 0.23–2.85, p = 0.751] at 1 year. Conclusions Patients with non-passable strictures can achieve symptomatic and endoscopic remission when receiving therapies used to treat CD, although they are less likely to obtain CR compared with patients without non-passable strictures. These findings support the importance of balancing the presence of non-passable strictures in trial arms.


2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S55-S55
Author(s):  
Marcin Sochal ◽  
Piotr Bialasiewicz ◽  
Agata Gabryelska ◽  
Renata Talar-Wojnarowska ◽  
Jakub Fichna ◽  
...  

Abstract Background and aims Serotonin affects intestinal physiology, mood, as well as circadian rhythm. Moreover, serotonin has proinflammatory function. Therefore, the aim of this study was to investigate the role of serotonin in clinical severity of Crohn’s Disease (CD) and its effect on pain and sleep quality. Methods Fifty-nine CD patients (34 in exacerbation and 25 in remission according to the Harvey-Bradshaw Index-HBI) and 25 health control individuals(HC) were recruited. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and subjective severity of pain by the Visual Analog Scale (VAS). Seventeen patients were treated with anti-TNF-α induction therapy for 14 weeks. Results Serotonin level was higher in CD (145.12ng/mL, IQR:98.14–179.25) compared to HC (87.52ng/mL, IQR:70.04–129.39; p=0.002) and in exacerbation of CD (157.66ng/mL, IQR:111.94–197.64) compared to remission (122.33ng/mL, IQR:83.28–163.67; p=0.029). Serotonin level with cut-off point of 92.45 ng/mL is useful for distinguishing participants with CD from HC (sensitivity: 78%, specificity: 60%, positive predictive value: 82%). Positive correlation between serotonin and HBI (r=0.279, p=0.032) and severity of diarrhoea (r=0.260, p=0.047) were found. Serotonin does not correlate with PSQI (r=0.152, p=0.168), but correlates with presence of sleep fragmentation for example by getting up to use the bathroom (joined 5b-5j PSQI questions; r=0.270, p=0.039). Correlations between serotonin and VAS were also obtained (r=0.220, p=0.045). Moreover, serotonin level significantly decreased after anti-TNF-α therapy (192.35ng/mL, IQR:150.36–225.56 vs. 121.11ng/mL, IQR:91.28–188.87; p=0.006). The study was funded by National Science Centre, Poland (#2018/31/N/NZ5/03715). Conclusions Serotonin level correlates with the severity of CD and decreases after anti-TNF-α therapy. It is associated with sleep fragmentation, which may be caused by diarrhea.


2019 ◽  
Vol 26 (7) ◽  
pp. 1050-1058 ◽  
Author(s):  
Robert P Hirten ◽  
Ryan C Ungaro ◽  
Daniel Castaneda ◽  
Sarah Lopatin ◽  
Bruce E Sands ◽  
...  

Abstract Background Crohn’s disease recurrence after ileocolic resection is common and graded with the Rutgeerts score. There is controversy whether anastomotic ulcers represent disease recurrence and should be included in the grading system. The aim of this study was to determine the impact of anastomotic ulcers on Crohn’s disease recurrence in patients with prior ileocolic resections. Secondary aims included defining the prevalence of anastomotic ulcers, risk factors for development, and their natural history. Methods We conducted a retrospective cohort study of patients undergoing an ileocolic resection between 2008 and 2017 at a large academic center, with a postoperative colonoscopy assessing the neoterminal ileum and ileocolic anastomosis. The primary outcome was disease recurrence defined as endoscopic recurrence (&gt;5 ulcers in the neoterminal ileum) or need for another ileocolic resection among patients with or without an anastomotic ulcer in endoscopic remission. Results One hundred eighty-two subjects with Crohn’s disease and an ileocolic resection were included. Anastomotic ulcers were present in 95 (52.2%) subjects. No factors were associated with anastomotic ulcer development. One hundred eleven patients were in endoscopic remission on the first postoperative colonoscopy. On multivariable analysis, anastomotic ulcers were associated with disease recurrence (adjusted hazard ratio [aHR] 3.64; 95% CI, 1.21–10.95; P = 0.02). Sixty-six subjects with anastomotic ulcers underwent a second colonoscopy, with 31 patients (79.5%) having persistent ulcers independent of medication escalation. Conclusion Anastomotic ulcers occur in over half of Crohn’s disease patients after ileocolic resection. No factors are associated with their development. They are associated with Crohn’s disease recurrence and are persistent.


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