Elevated colonic microbiota-associated paucimannosidic and truncated N-glycans in pediatric ulcerative colitis

Pediatric ulcerative colitis (UC) is a distinct type of inflammatory bowel disease with severe disease activity and rapid progression, which can lead to detrimental life-long consequences. The pathogenesis of pediatric UC remains unclear, although dysbiosis of the gut microbiota has been considered an important factor. In this study, we used mass spectrometry-based glycomic approaches to examine the N-glycans that were associated with the intestinal mucosal-luminal interface microbiota cells of treatment-naive pediatric UC or control patients. We observed abundant paucimannosidic and other truncated N-glycans that were associated with the microbiota and found that the pediatric UC microbiota samples contained significantly higher levels of these atypical N-glycans compared to those of controls. This study indicates that intestinal N-glycans may be used as novel UC biomarker candidates and the aberrant metabolism of glycans by gut microbiota may be involved in the pathogenesis of UC in children.

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An Overview of Novel and Emerging Therapies for Inflammatory Bowel Disease

EMJ Gastroenterology ◽

10.33590/emjgastroenterol/20-00166 ◽

2020 ◽

pp. 91-101

Author(s):

Sumona Bhattacharya Sumona Bhattacharya ◽

Raymond K. Cross Raymond K. Cross

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Severe Disease ◽

Gastrointestinal Symptoms ◽

The Novel ◽

Novel Therapies ◽

Emerging Therapies ◽

Sphingosine 1 Phosphate ◽

Inflammatory Bowel

Inflammatory bowel disease, consisting of Crohn’s disease and ulcerative colitis, causes chronic gastrointestinal symptoms and can lead to morbidity and mortality if uncontrolled or untreated. However, for patients with moderate-to-severe disease, currently available therapies do not induce or maintain remission in >50% of patients. This underscores the need for additional therapies. In this review, the authors detail the novel therapies vedolizumab, tofacitinib, and ustekinumab and delve into therapies which may come onto the market within the next 10 years, including JAK-1 inhibitors (filgotinib and upadacitinib), IL-23 inhibitors (guselkumab, mirikizumab, and risankizumab), the anti-β4β7 and anti-βEβ7 integrin monoclonal antibody etrolizumab, the sphingosine-1-phosphate subtypes 1 and 5 modulator ozanimod, and mesenchymal stem cells. Further studies are required before these emerging therapies gain approval.

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Gut Microbiota Profile in Pediatric Patients With Inflammatory Bowel Disease: A Systematic Review

Frontiers in Pediatrics ◽

10.3389/fped.2021.626232 ◽

2021 ◽

Vol 9 ◽

Author(s):

Xiaojun Zhuang ◽

Caiguang Liu ◽

Shukai Zhan ◽

Zhenyi Tian ◽

Na Li ◽

...

Keyword(s):

Systematic Review ◽

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Bowel Disease ◽

Pediatric Patients ◽

Β Diversity ◽

Α Diversity ◽

Treatment Naïve ◽

Inflammatory Bowel ◽

Pediatric Ibd

Background and Aim: Accumulating evidence have implicated gut microbiota alterations in pediatric and adult patients with inflammatory bowel disease (IBD); however, the results of different studies are often inconsistent and even contradictory. It is believed that early changes in new-onset and treatment-naïve pediatric patients are more informative. We performed a systematic review to investigate the gut microbiota profiles in pediatric IBD and identify specific microbiota biomarkers associated with this disorder.Methods: Electronic databases were searched from inception to 31 July 2020 for studies that observed gut microbiota alterations in pediatric patients with IBD. Study quality was assessed using the Newcastle–Ottawa scale.Results: A total of 41 original studies investigating gut microbiota profiles in pediatric patients with IBD were included in this review. Several studies have reported a decrease in α-diversity and an overall difference in β-diversity. Although no specific gut microbiota alterations were consistently reported, a gain in Enterococcus and a significant decrease in Anaerostipes, Blautia, Coprococcus, Faecalibacterium, Roseburia, Ruminococcus, and Lachnospira were found in the majority of the included articles. Moreover, there is insufficient data to show specific microbiota bacteria associated with disease activity, location, and behavior in pediatric IBD.Conclusions: This systematic review identified evidence for differences in the abundance of some bacteria in pediatric patients with IBD when compared to patients without IBD; however, no clear overall conclusion could be drawn from the included studies due to inconsistent results and heterogeneous methodologies. Further studies with large samples that follow more rigorous and standardized methodologies are needed.

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AN ADVANCED REVIEW ON DIAGNOSIS AND TREATMENT AND EXTRA-INTESTINAL MANIFESTATIONS ASSOCIATED WITH INFLAMMATORY BOWEL DISEASE

Journal of Biomedical and Pharmaceutical Research ◽

10.32553/jbpr.v10i1.848 ◽

2021 ◽

Vol 10 (1) ◽

pp. 99-113

Author(s):

Deep Sharma ◽

Rekha Rana ◽

Kiran Thakur ◽

Priyanka

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Inflammatory Bowel Diseases ◽

Bowel Disease ◽

Severe Disease ◽

Clinical Pathology ◽

Bowel Diseases ◽

Inflammatory Bowel

Inflammatory Bowel Diseases are mainly a group of bowel disorders which are generally associated with chronic inflammation of the intestinal tract due to the reason of an imbalance in the presence of the intestinal microbiota. Inflammatory bowel disease can have two different types based on their clinical pathology which are mainly Crohn’s Disease and Ulcerative Colitis. Both of these clinical sub-types are most likely to be focussed among all of the inflammatory bowel diseases due to their increasing risk of incidence as well as associated difficulties in their treatment. However, the main cause of inflammatory bowel disease has not been cleared till the date but from last three decades, there is a hub of researchnes being going on to get a clear idea about the cause of disease. Among these studies most of researchers have found the role of Nucleotide Oligomerization Domain 2 genes in the pathophysiology of disease. For the treatment of ulcerative colitis, there are severalapproaches available, based on the severity of the disease. Aminosalicylates are used to treat mild disease, use of corticosteroids is the effective treatment in the moderate case whereas use of cyclosporine in severe disease. In Crohn’s disease, drug choices are dependent on both location and behavior ofthe disease. Nowadays, the advanced treatments have been included such as use of monoclonal antibodiesor fusion proteins including anti-TNF drugs as biological therapy of disease. Also the post treatment remission of this disease makes it more complicated to be cured.

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P125 Could gut microbiota metagenomic analysis improve diagnosis in paediatric Inflammatory Bowel Disease population?

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.252 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S216-S217

Author(s):

G Pujol Muncunill ◽

A Monleon-Getino ◽

J Méndez-Viera ◽

L Álvarez-Carnero ◽

J Martin de Carpi

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Gut Microbiota ◽

Diagnostic Tool ◽

Bowel Disease ◽

Inflammatory Markers ◽

Activity Index ◽

Healthy Controls ◽

Inflammatory Bowel

Abstract Background Gut microbiota plays an important role in maintaining intestinal homeostasis. Recent studies postulate that dysbiosis may be involved in the pathogenesis of Inflammatory Bowel Disease (IBD). The aim of the study was to characterize the metagenomic biodiversity of the gut microbiota in Paediatric Inflammatory Bowel Disease patients (PIBD) and whether microbiome data could be used as diagnostic tool. Methods A prospective, longitudinal observational pilot clinical trial with consecutive inclusion of PIBD patients matched with healthy controls by age and sex was performed. A total of 36 children were planned to be included: 12 Crohn’s Disease (CD), 12 Ulcerative Colitis (UC) and 12 healthy controls (HC). Demographic, clinical and analytical data were recorded and stool and saliva samples were collected at onset, 3 and 6 months for DNA sequencing and bioinformatics analysis. Results Twenty-three patients (12CD, 11UC) and 9 HC were included (at the time of data analysis). Fifty-six percent were male; mean age: 11.7 years (IQR: 8–15). CD patients at onset had a mean Paediatric Crohn’s Disease Activity Index (PCDAI) of 22.5 (IQR: 10–55), a mean Faecal Calprotectin (FC) of 2384 mg/kg (IQR: 159–6000) and 83% of them had inflammatory markers elevation (Erythrocyte Sedimentation Rate (ESR) and/or C-reactive protein (CRP)). Patients with UC presented a mean Paediatric Ulcerative Colitis Activity Index (PUCAI) of 43.6 (IQR: 10–80) at onset, mean CF of 3381 mg/kg and 18% presented an increase of inflammatory markers (ESR and/or CRP). To date, Next Generation Sequencing (NGS) metagenomic study (saliva and stools) has been performed from 15 subjects (9 CD, 2 UC and 4 HC) at onset and 9 subjects (7 CD and 2 UC) at 3 months. A differential microbiota pattern was observed in both, saliva and stools, for CD at onset and at 3 months. In the stools, three differential taxa were found at onset of the disease and at 3 months and in saliva, another three differential taxa were observed compared to HC. In UC, 6 differential taxa (> 3 % diff. HC-UC, p-value=0) were selected in stools and 7 in saliva at onset compared to HC. Globally, a higher microbial biodiversity was observed for HC compared to CD at onset, but it was not statistically significant. Conclusion Provisional results showed a possible differential signature in both saliva and stools of patients with paediatric CD. These results must be validated with all the samples in process, and probably using larger paediatric cohorts before the development of these techniques as a diagnostic tool in the clinical practice.

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A propensity score-weighted comparison between adalimumab originator and its biosimilars, ABP501 and SB5, in inflammatory bowel disease: a multicenter Italian study

Therapeutic Advances in Gastroenterology ◽

10.1177/17562848211031420 ◽

2021 ◽

Vol 14 ◽

pp. 175628482110314

Author(s):

Brigida Barberio ◽

Linda Cingolani ◽

Cristina Canova ◽

Giulia Barbieri ◽

Renato Sablich ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Propensity Score ◽

Bowel Disease ◽

Clinical Benefit ◽

Severe Disease ◽

Real Life ◽

Great Opportunity ◽

Significant Difference ◽

Inflammatory Bowel

Background: Adalimumab is an effective and safe biological drug for the treatment of inflammatory bowel disease (IBD). Nowadays, several biosimilar agents are available, but data regarding their efficacy and safety in patients with IBD are still lacking. We aimed to compare the effectiveness and tolerability between adalimumab originator, ABP501 and SB5 biosimilars in patients with IBD in the short term (after induction and after 6 months of treatment) through a propensity score-weighted multicenter cohort study. Methods: We included 156 patients with IBD, 69 patients with ulcerative colitis and 87 patients with Crohn’s disease (CD) receiving ABP501 or SB5 biosimilars from January 2019 to April 2020 for moderate-to-severe disease. For comparison, a group of age- and sex-matched patients treated with adalimumab originator was used. We collected clinical and biochemical data after induction and at 6 months of treatment. Endoscopic data were recorded only at baseline. Results: Overall, clinical benefit was achieved by 86.4% and 85.3% after induction and at 6 months, respectively, without a statistically significant difference between the three treatment groups ( p = 0.68 and p = 0.46). However, after induction, we found significant differences between the two types of the disease (ulcerative colitis or CD, p = 0.004), with a greater clinical benefit achieved by patients with CD. Also, the therapeutic optimization rate between the three drugs was not statistically significant different ( p = 0.30). All treatments showed a good safety profile, with only 10 patients who needed to stop therapy because of adverse events. Conclusion: Adalimumab biosimilars seem to be as effective and safe as the originator in patients with IBD. Surely, they represent a great opportunity to reduce the costs of biological therapies, however larger and longer real-life studies are necessary.

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Rapid Progression of Primary Sclerosing Cholangitis Complicated with Ulcerative Colitis

Case Reports in Gastrointestinal Medicine ◽

10.1155/2015/125718 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4

Author(s):

Piotr Pardak ◽

Ewa Walczak ◽

Rafał S. Filip

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Liver Transplant ◽

Primary Sclerosing Cholangitis ◽

Bowel Disease ◽

Sclerosing Cholangitis ◽

Unknown Etiology ◽

Rapid Progression ◽

Inflammatory Bowel ◽

Progressive Course

Primary sclerosing cholangitis is a cholestatic condition with unknown etiology and long-standing, progressive course, leading to cirrhosis and requiring orthotropic liver transplant. In approximately 80%, primary sclerosing cholangitis is accompanied by inflammatory bowel disease, and in most cases the recognition of bowel disease precedes the diagnosis of primary sclerosing cholangitis. We describe a case of 22-year-old male diagnosed simultaneously with primary sclerosing cholangitis and ulcerative colitis, with a medical history suggesting uncommon prior development of the liver disease. Five months after the initial diagnosis, we observed advanced lesions of bile tree due to progression of primary sclerosing cholangitis, which led to the unusually fast necessity for the orthotopic liver transplant.

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