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Pharmaceuticals
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Drugs and Treatments for Inflammatory Bowel Diseases
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Drugs and Treatments for Inflammatory Bowel Diseases

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 16822

Special Issue Editors

Dr. Maciej Sałaga

E-Mail Website
Guest Editor
Department of Biochemistry, Medical University of Lodz, Lodz, Poland
Interests: IBD; IBS; cannabinoid system; G protein coupled receptors; opioid receptors; intestinal epithelium; cell death
Dr. Marta Zielińska

E-Mail Website
Guest Editor
Department of Biochemistry, Medical University of Lodz, Lodz, Poland
Interests: IBD; IBS; cannabinoid system; G protein coupled receptors; opioid receptors; intestinal epithelium; cell death

Special Issue Information

Dear Colleagues,

Inflammatory bowel disease (IBD) is a group of chronic, relapsing disorders of the gastrointestinal (GI) tract that significantly affect patients’ quality of life. The main goals of IBD treatment are long-lasting clinical remission without serious adverse events. The lack of fully effective treatment urges researchers to seek new therapeutic strategies and design of novel anti-inflammatory compounds.

In this Special Issue, we focus on the latest advances in IBD therapy. We aim to characterize the clinical efficacy and mechanism of action of stem-cell-, antibody- and small-molecule-based methods of treatment that have already reached the clinic or are currently evaluated in clinical studies. Moreover, we will cover the topic of plant-based and diet-based interventions that may be used in IBD therapy. We will also describe recent advances in the discovery of biomarkers in IBD.

Dr. Maciej Sałaga
Dr. Marta Zielińska
Guest Editors

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Keywords

  • Inflammatory bowel disease
  • Ulcerative colitis
  • Crohn’s disease
  • Biological therapy
  • JAK inhibitors
  • Integrins
  • Stem cell therapy
  • Intestinal epithelium
  • Cell death
  • Enteric nervous system

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Published Papers (5 papers)

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Research

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13 pages, 725 KiB  
Article
Vitamin D-Related Genetics as Predictive Biomarker of Clinical Remission in Adalimumab-Treated Patients Affected by Crohn’s Disease: A Pilot Study
by Jessica Cusato, Lorenzo Bertani, Miriam Antonucci, Cristina Tomasello, Gian Paolo Caviglia, Simone Dibitetto, Alessandro Massano, Michela Mangia, Jacopo Mula, Linda Ceccarelli, Francesco Costa, Federico Zanzi, Marco Astegiano, Davide Giuseppe Ribaldone and Antonio D’Avolio
Pharmaceuticals 2021, 14(12), 1230; https://doi.org/10.3390/ph14121230 - 27 Nov 2021
Cited by 5 | Viewed by 2883
Abstract
Adalimumab (ADA) is a human anti-tumor necrosis factor (TNF-α) monoclonal antibody used in inflammatory bowel diseases, such as Crohn’s disease (CD). Vitamin-D (VD) is important for biological functions, such as the modulation of expression of genes encoding enzymes and transporters involved in drug [...] Read more.
Adalimumab (ADA) is a human anti-tumor necrosis factor (TNF-α) monoclonal antibody used in inflammatory bowel diseases, such as Crohn’s disease (CD). Vitamin-D (VD) is important for biological functions, such as the modulation of expression of genes encoding enzymes and transporters involved in drug metabolism and transport. ADA trough levels were associated with VD concentrations in patients with IBD, but no data are present in the literature concerning VD pathway-related gene single-nucleotide polymorphisms (SNPs) in affecting clinical outcomes. For this reason, the aim of this study was to evaluate the ability of VD-related genetics to predict clinical remission at 3 and 12 months in patients affected by CD treated with ADA. Patients affected by CD were included in this study. SNPs in CYP27B1, CYP24A1, GC, and VDR genes were analyzed through real-time PCR. A total of 63 patients were enrolled. Calprotectin, hemoglobin, and C-reactive protein levels were influenced by SNPs in VDR, CYP27B1, and GC genes. After 3 months of therapy, clinical remission was predicted by smoke, systemic steroids, and VDR BsmI, whereas at 12 months by GC 1296AA/AC and VD supplementation. This study reports the association between VD pathway-related genetics and ADA treatment. Further studies are needed to confirm these promising data. Full article
(This article belongs to the Special Issue Drugs and Treatments for Inflammatory Bowel Diseases)
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9 pages, 1306 KiB  
Article
Potential Role of Methotrexate Polyglutamates in Therapeutic Drug Monitoring for Pediatric Inflammatory Bowel Disease
by Ryan Morrow, Ryan Funk, Mara Becker, Ashley Sherman, Leon Van Haandel, Taina Hudson, Rebecca Casini and Valentina Shakhnovich
Pharmaceuticals 2021, 14(5), 463; https://doi.org/10.3390/ph14050463 - 14 May 2021
Cited by 5 | Viewed by 2551
Abstract
Inside cells, the immunomodulator methotrexate (MTX) undergoes the addition of glutamates to form methotrexate polyglutamates (MTX-Glu)—promising biomarkers of systemic exposure and treatment response to MTX in rheumatology. MTX-Glu are underexplored in Inflammatory Bowel Disease (IBD), with no data in pediatrics. In this cross-sectional [...] Read more.
Inside cells, the immunomodulator methotrexate (MTX) undergoes the addition of glutamates to form methotrexate polyglutamates (MTX-Glu)—promising biomarkers of systemic exposure and treatment response to MTX in rheumatology. MTX-Glu are underexplored in Inflammatory Bowel Disease (IBD), with no data in pediatrics. In this cross-sectional secondary analysis, we assessed the relationships between MTX-Glu and MTX dose and treatment response in pediatric IBD. Twenty-one children with IBD, receiving maintenance therapy with infliximab (IFX) and MTX, had MTX-Glu1–6 concentrations and IFX troughs/antibodies measured and disease activity assessed for comparison in remission vs. active IBD using non-parametric tests, with associations explored using Spearman’s correlation (ρ) and regression analyses; SASv9.4 (α = 0.05). Total and long-chain MTX-Glu correlated with MTX dose (ρ = 0.51 and 0.56, respectively; p ≤ 0.02). In children with Crohn’s disease (n = 19), short-chain MTX-Glu1–2 were 2.5-fold higher in remission vs. active disease, approaching statistical significance (p = 0.066), with no statistical differences in IFX trough (p = 0.549) between groups. Our study highlights a potential role for long-chain MTX-Glu in the therapeutic drug monitoring of MTX in IBD. It is the first study in pediatric IBD and, although statistical significance was not reached, our findings also suggest that higher short-chain MTX-Glu levels may be associated with IBD treatment response to MTX in children. Full article
(This article belongs to the Special Issue Drugs and Treatments for Inflammatory Bowel Diseases)
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17 pages, 4130 KiB  
Article
Fermented Maillard Reaction Products by Lactobacillus gasseri 4M13 Alters the Intestinal Microbiota and Improves Dysfunction in Type 2 Diabetic Mice with Colitis
by Yu-Jin Jeong, Ho-Young Park, Han-Kyul Nam and Kwang-Won Lee
Pharmaceuticals 2021, 14(4), 299; https://doi.org/10.3390/ph14040299 - 28 Mar 2021
Cited by 5 | Viewed by 3187
Abstract
Inflammatory bowel disease is a chronic relapsing disease. Multiple factors can cause inflammatory bowel disease (IBD), including diet, imbalance of the immune system, and impaired intestinal barrier function. Type 2 diabetes mellitus is a complex and chronic metabolic disease caused by a combination [...] Read more.
Inflammatory bowel disease is a chronic relapsing disease. Multiple factors can cause inflammatory bowel disease (IBD), including diet, imbalance of the immune system, and impaired intestinal barrier function. Type 2 diabetes mellitus is a complex and chronic metabolic disease caused by a combination of insulin resistance and an ineffective insulin secretory response. The co-occurrence of these two diseases, demonstrating interrelated effects within the gut microbiota, has been frequently reported. This study evaluated the effects of a fermented glycated conjugate of whey protein and galactose with Lactobacillus gasseri 4M13 (FMRP) to prevent type 2 diabetes mellitus with inflammatory bowel disease. C57BLKS/J- db/db mice were orally administered FMRP for 14 consecutive days and 2% dextran sulfate sodium (DSS) in water ad libitum for 5 days to induce colitis. FMRP-fed mice showed improved insulin secretion and symptoms of colitis. Compared to the DSS group, the FMRP group showed a decreased abundance of six bacterial genera and increased abundance of Alistipes and Hungateiclostridium. In cecal contents, the levels of short-chain fatty acids increased in the FMRP group compared to those in the DSS group. Continuous administration of FMRP thus may improve the homeostasis of not only insulin secretion and inflammation, but also the intestinal environment in inflammatory bowel disease and type 2 diabetes mellitus. Full article
(This article belongs to the Special Issue Drugs and Treatments for Inflammatory Bowel Diseases)
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14 pages, 2869 KiB  
Article
The 25(OH)D3, but Not 1,25(OH)2D3 Levels Are Elevated in IBD Patients Regardless of Vitamin D Supplementation and Do Not Associate with Pain Severity or Frequency
by Anna Zielińska, Aleksandra Sobolewska-Włodarczyk, Maria Wiśniewska-Jarosińska, Anita Gąsiorowska, Jakub Fichna and Maciej Sałaga
Pharmaceuticals 2021, 14(3), 284; https://doi.org/10.3390/ph14030284 - 22 Mar 2021
Cited by 5 | Viewed by 2678
Abstract
Due to its immunomodulatory effect, vitamin D has been associated with clinical parameters and outcomes in inflammatory bowel diseases (IBDs) which are chronic conditions of the gastrointestinal tract. Upon synthesis or digestion, vitamin D is metabolized in the liver to form 25(OH)D3, the [...] Read more.
Due to its immunomodulatory effect, vitamin D has been associated with clinical parameters and outcomes in inflammatory bowel diseases (IBDs) which are chronic conditions of the gastrointestinal tract. Upon synthesis or digestion, vitamin D is metabolized in the liver to form 25(OH)D3, the major circulating metabolite. Further renal hydroxylation generates 1,25(OH)2D3, the most potent metabolite. Our aim was to examine the association between vitamin D levels, and its supplementation and pain intensity in 39 IBD patients and 33 healthy individuals. 25(OH)D3 and 1,25(OH)2D3 serum levels were measured. Each subject filled out visual analog scale (VAS) and Laitinen’s pain assessment scales. Laboratory results were obtained, and disease activity was assessed. Linear regression was employed to investigate the correlation between 25(OH)D3, 1,25(OH)2D3 and pain intensity, clinical activity parameters, C-reactive protein, disease duration, and dietary habits. In IBD patients, 25(OH)D3 was increased, whereas 1,25(OH)2D3 was not. Vitamin D3 supplementation did not influence their levels. No correlation was found between pain scores, disease activity, inflammatory status, disease duration or dietary habits and both forms of vitamin D. Elevated 25(OH)D3 and normal 1,25(OH)D3 were found in IBD patients as compared to the controls. We discovered no effect from supplementation and no association between pain severity and vitamin D. Full article
(This article belongs to the Special Issue Drugs and Treatments for Inflammatory Bowel Diseases)
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Review

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20 pages, 1372 KiB  
Review
Small Molecule Drugs in Inflammatory Bowel Diseases
by Inès Ben Ghezala, Maëva Charkaoui, Christophe Michiels, Marc Bardou and Maxime Luu
Pharmaceuticals 2021, 14(7), 637; https://doi.org/10.3390/ph14070637 - 30 Jun 2021
Cited by 16 | Viewed by 5079
Abstract
Inflammatory bowel diseases (IBDs), mainly represented by Crohn’s disease (CD) and Ulcerative Colitis (UC), are chronic disorders with an unclear pathogenesis. This incurable and iterative intestinal mucosal inflammation requires the life-long use of anti-inflammatory drugs to prevent flares or relapses, which are the [...] Read more.
Inflammatory bowel diseases (IBDs), mainly represented by Crohn’s disease (CD) and Ulcerative Colitis (UC), are chronic disorders with an unclear pathogenesis. This incurable and iterative intestinal mucosal inflammation requires the life-long use of anti-inflammatory drugs to prevent flares or relapses, which are the major providers of complications, such as small bowel strictures and intestinal perforations. The introduction of tumor necrosis factor (TNF)-alpha inhibitors and other compounds, such as anti-IL12/23 and anti-alpha4/beta7 integrin monoclonal antibodies, has considerably improved the clinical management of IBDs. They are now the standard of care, being the first-line therapy in patients with aggressive disease and in patients with moderate to severe disease with an inadequate response to conventional therapy. However, for approximately one third of all patients, their efficacy remains insufficient by a lack or loss of response due to the formation of anti-drug antibodies or compliance difficulties with parenteral formulations. To address these issues, orally administered Small Molecules Drugs (SMDs) that use a broad range of novel pharmacological pathways, such as JAK inhibitors, sphingosine-1-phosphate receptor modulators, and phosphodiesterase 4 inhibitors, have been developed for CD and UC. This article provides an updated and complete review of the most recently authorized SMDs and SMDs in phase II/III development. Full article
(This article belongs to the Special Issue Drugs and Treatments for Inflammatory Bowel Diseases)
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