Dataset Information

Changes in the Intestinal Microbiota Are Seen Following Treatment with Infliximab in Children with Crohn's Disease.

ABSTRACT: The aim of the study was to determine the impact of biological treatment with tumor necrosis factor ? antibodies (anti-TNF-?) 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-? 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.

SUBMITTER: Kowalska-Duplaga K

PROVIDER: S-EPMC7141282 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Changes in the Intestinal Microbiota Are Seen Following Treatment with Infliximab in Children with Crohn's Disease.

Kowalska-Duplaga Kinga K Kapusta Przemysław P Gosiewski Tomasz T Sroka-Oleksiak Agnieszka A Ludwig-Słomczyńska Agnieszka H AH Wołkow Paweł P PP Fyderek Krzysztof K

Journal of clinical medicine 20200304 3

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 pat ...[more]

PMID: 32143438

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Project description:BackgroundMucosal healing (MH) is the key aim of the treat-to-target strategy for patients with Crohn's disease (CD). The efficacy of infliximab (IFX) on MH in different ileocolonic segments is unclear. The aim of this study was to investigate endoscopic MH in different ileocolonic segments in patients with CD who received IFX treatment.MethodsA retrospective, single-center study was performed in patients with active ileocolonic CD between January 2012 and December 2018. All patients underwent IFX treatment for at least 30 weeks. The MH of five ileocolonic segments was assessed by the Simple Endoscopic Score for CD (SES-CD) at baseline, 14/22 weeks and 30/38 weeks. The SES-CD values were analyzed by a mixed-effects model after the correction for confounding factors.ResultsA total of 101 eligible patients were included. The baseline endoscopic severity was similar across segments. At 30/38 weeks, the greatest changes in the SES-CD ulcer size and ulcerated surface subscores were -94.29% and -94.32% both in the transverse colon (p < 0.0001), and the smallest changes were -67.88% and -69.67% both in the terminal ileum (p < 0.0001) compared with baseline. Stenosis mainly presented in the right colon (12/29, 41.38%). The change in the SES-CD stenosis subscore was -6.25% in the right colon at 30/38 weeks compared with -71.88% at 14/22 weeks (p = 0.0030). At 30/38 weeks, the transverse colon achieved the highest rate of complete MH (CMH) at 81.2%, and the lowest CMH rate occurred in the terminal ileum at 45.6%. Moreover, the degree of improvement in the rectum was negatively correlated with disease progression (p = 0.011).ConclusionsIleocolonic segments in CD presented different degrees of endoscopic MH during IFX treatment. The transverse colon showed the highest CMH rate, whereas the right colon with stenosis showed the poorest improvement. The differing propensities of ileocolonic segments may provide an individualized IFX treatment strategy.

Project description:BackgroundInflammatory bowel disease (IBD) is chronic inflammation of the gastrointestinal tract, although its etiology has largely been unclear. Tumor necrosis factor inhibitors (TNF-I) are effective for the treatment. Recently, biosimilars of TNF-I, such as CT-P13, have been developed and are thought to possess equal efficacy and safety to the original TNF-I. Sarcoidosis is also a systemic granulomatous disease of unknown etiology. In steroid-resistant cases of sarcoidosis, TNF-I have been reported effective for achieving resolution. However, the progression of sarcoidosis due to the TNF-I also has been reported. We herein report a case of pulmonary sarcoidosis with a Crohn's disease (CD) patient developed after a long period administration (15 years) of TNF-I.Case presentationsA 37-year-old woman with CD who had been diagnosed at 22 years old had been treated with the TNF-I (original infliximab; O-IFX and infliximab biosimilar; IFX-BS). Fifteen years after starting the TNF-I, she developed a fever and right chest pain. Chest computed tomography (CT) revealed clustered small nodules in both lungs and multiple enlarged hilar lymph nodes. Infectious diseases including tuberculosis were negative. Bronchoscopic examination was performed and the biopsy specimens were obtained. A pathological examination demonstrated noncaseating granulomatous lesions and no malignant findings. TNF-I were discontinued because of the possibility of TNF-I-related sarcoidosis. After having discontinued for four months, her symptoms and the lesions had disappeared completely. Fortunately, despite the discontinuation of TNF-I, she has maintained remission.ConclusionsTo our knowledge, this is the first case in which sarcoidosis developed after switching from O-IFX to IFX-BS. To clarify the characteristics of the cases with development of sarcoidosis during administration of TNF-I, we searched PubMed and identified 106 cases. When developing an unexplained fever, asthenia, uveitis and skin lesions in patients with TNF-I treatment, sarcoidosis should be suspected. Once the diagnosis of sarcoidosis due to TNF-I was made, the discontinuation of TNF-I and administration of steroid therapy should be executed promptly. When re-starting TNF-I, another TNF-I should be used for disease control. Clinicians should be aware of the possibility of sarcoidosis in patients under anti-TNF therapy.

Dataset Information

Changes in the Intestinal Microbiota Are Seen Following Treatment with Infliximab in Children with Crohn's Disease.

Publications

Changes in the Intestinal Microbiota Are Seen Following Treatment with Infliximab in Children with Crohn's Disease.

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