Biomedicines

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11 pages, 7612 KiB

Open AccessArticle

Sirtuin 7 Inhibitor Attenuates Colonic Mucosal Immune Activation in Mice—Potential Therapeutic Target in Inflammatory Bowel Disease

by Sanghyun Kim, Junhyoung Byun, Semyung Jung, Byoungjae Kim, Kangwon Lee, Hanjo Jeon, Jaemin Lee, Hyuksoon Choi, Eunsun Kim, Yoontae Jeen, Hongsik Lee, Hoonjai Chun, Bora Keum and Taehoon Kim

Biomedicines 2022, 10(11), 2693; https://doi.org/10.3390/biomedicines10112693 - 25 Oct 2022

Cited by 4 | Viewed by 1847

Abstract

Accumulating evidence has shown that sirtuin 7 (SIRT7), a mediator of various cellular activities, plays an important role in the pathogenesis of various immune-mediated inflammatory disorders. However, information remains limited regarding the role of SIRT7 in intestinal inflammation. We used a murine colitis [...] Read more.

Accumulating evidence has shown that sirtuin 7 (SIRT7), a mediator of various cellular activities, plays an important role in the pathogenesis of various immune-mediated inflammatory disorders. However, information remains limited regarding the role of SIRT7 in intestinal inflammation. We used a murine colitis model to investigate the role of SIRT7 in intestinal immunity and whether SIRT7 inhibitors could attenuate the intestinal inflammatory response. Mice were divided into three groups: control, colitis-induced, and SIRT7-inhibitor-treated. A colitis mouse model was established by intraperitoneal injection and nasal challenge with ovalbumin, as in our previous study. Quantitative analyses of inflammatory cytokines and SIRT7 levels in the colonic mucosa were performed to compare the changes in inflammatory responses between the three groups. The colitis group showed increased levels of inflammatory cytokines and SIRT7 in the colonic mucosa. The inflammatory reaction was suppressed in colitis-induced mice administered the SIRT7 inhibitor. The qRT-PCR results showed normalization of inflammatory cytokines in the SIRT7 inhibitor-treated group. Histologic study revealed a decrease in the extent of inflammation after SIRT7 treatment. We also observed that the degree of clinical inflammation was improved in SIRT7-treated mice. Our study demonstrated that SIRT7 inhibition attenuated the inflammatory response in the colon of mice, suggesting a possible role for SIRT7 in the pathogenesis of immune-mediated intestinal inflammation. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

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9 pages, 390 KiB

Open AccessArticle

Disease- and Medication-Specific Differences of the Microbial Spectrum in Perianal Fistulizing Crohn’s Disease—Relevant Aspects for Antibiotic Therapy

by Matthias Kelm, Simon Kusan, Güzin Surat, Friedrich Anger, Joachim Reibetanz, Christoph-Thomas Germer, Nicolas Schlegel and Sven Flemming

Biomedicines 2022, 10(11), 2682; https://doi.org/10.3390/biomedicines10112682 - 23 Oct 2022

Cited by 4 | Viewed by 1535

Abstract

Perianal fistulizing Crohn’s Disease (CD) with abscess formation represents an aggressive phenotype in Inflammatory Bowel Disease (IBD) with increased morbidity. Treatment is multidisciplinary and includes antibiotics, but knowledge about the microbial spectrum is rare often resulting in inadequate antimicrobial therapy. In this single [...] Read more.

Perianal fistulizing Crohn’s Disease (CD) with abscess formation represents an aggressive phenotype in Inflammatory Bowel Disease (IBD) with increased morbidity. Treatment is multidisciplinary and includes antibiotics, but knowledge about the microbial spectrum is rare often resulting in inadequate antimicrobial therapy. In this single center retrospective study, all patients who were operated due to perianal abscess formation were retrospectively analyzed and the microbial spectrum evaluated. Patients were divided into a CD and non-CD group with further subgroup analysis. 138 patients were finally included in the analysis with 62 patients suffering from CD. Relevant differences were detected for the microbial spectrum with anaerobic bacteria being significantly more often isolated from non-CD patients. In a subgroup-analysis of CD patients only, medical therapy had a relevant effect on the microbial spectrum since Streptococcus groups and Enterobacterales were significantly more often isolated in patients treated with steroids compared to those being treated by antibodies. In conclusion, the microbial spectrum of patients suffering from CD varies significantly from non-CD patients and immunosuppressive medication has a relevant effect on isolated pathogens. Based on that, adaption of antibiotic treatment might be discussed in the future. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

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8 pages, 455 KiB

Open AccessArticle

Enhanced Recovery Care versus Traditional Care after Surgery in Pediatric Patients with Inflammatory Bowel Disease: A Retrospective Case-Control Study

by Valeria Dipasquale, Francesca Laganà, Serena Arrigo, Giuseppe Trimarchi, Carmelo Romeo, Giuseppe Navarra, Girolamo Mattioli, Paolo Gandullia and Claudio Romano

Biomedicines 2022, 10(9), 2209; https://doi.org/10.3390/biomedicines10092209 - 7 Sep 2022

Cited by 3 | Viewed by 1831

Abstract

This study reports the outcomes of an enhanced recovery after surgery (ERAS) protocol in pediatric inflammatory bowel disease (IBD) surgery. Children who underwent surgery for IBD at two academic referral centers from January 2016 to June 2021 were included. Preoperative counseling, early enteral [...] Read more.

This study reports the outcomes of an enhanced recovery after surgery (ERAS) protocol in pediatric inflammatory bowel disease (IBD) surgery. Children who underwent surgery for IBD at two academic referral centers from January 2016 to June 2021 were included. Preoperative counseling, early enteral feeding (Impact^®, Nestlé Health Science, and early mobilization were all part of the ERAS protocol. The outcomes (timing of first defecation, postoperative complications, and length of hospital stay (LOS)) were compared to traditional perioperative regimens (non-ERAS group). Thirty-three children who had 61 abdominal surgeries for IBD were included. Forty (65.5%) surgical procedures were included in the non-ERAS group, and 21 (34.5%) were included in the ERAS group. The postoperative complication rate was significantly lower in the ERAS group than in the non-ERAS group (29.6% vs. 55%, p = 0.049). The first defecation occurred earlier in the ERAS group than in the non-ERAS group (p < 0.001). There was no significant intergroup difference in the LOS. The implementation of ERAS in pediatric IBD surgery resulted in better outcomes than traditional perioperative care, especially in terms of postoperative complication rate and bowel function recovery. Further pediatric studies are needed to validate these findings and support ERAS application in children. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

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11 pages, 683 KiB

Open AccessArticle

Subcutaneous Infliximab [CT-P13], a True Biologic 2.0. Real Clinical Practice Multicentre Study

by Jose M. Huguet, Victor García-Lorenzo, Lidia Martí, Jose María Paredes, Jose Joaquin Ramírez, Miguel Pastor, Lucia Ruiz, Ana Sanahuja, Pilar Timoneda, Laura Sanchís, Gloria Alemany Pérez and Marta Maia Boscá-Watts

Biomedicines 2022, 10(9), 2130; https://doi.org/10.3390/biomedicines10092130 - 30 Aug 2022

Cited by 21 | Viewed by 3002

Abstract

Background: Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is characterized by chronic relapsing intestinal inflammation. There are few data on the efficacy and safety in clinical practice of infliximab (CT-P13) in subcutaneous formulation (SC) for the treatment of patients with [...] Read more.

Background: Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is characterized by chronic relapsing intestinal inflammation. There are few data on the efficacy and safety in clinical practice of infliximab (CT-P13) in subcutaneous formulation (SC) for the treatment of patients with IBD. Methods: Multicenter, prospective study of patients with IBD in clinical remission, who had their treatment changed from intravenous (IV) infliximab to SC. Two groups of patients were evaluated according to whether they were on IV infliximab treatment at standard or intensified doses before the switch. Results: A total of 30 patients were on standard dosing and another 30 in intensified therapy. Treatment persistence in both groups at 6 months was greater than 95%. In both groups after the change, neither the biomarkers of inflammation nor the activity indices underwent significant changes at 3 and 6 months compared to the baseline value. Similarly, in both groups, infliximab trough levels showed a significant increase 3 and 6 months after the change to SC. No serious adverse events were registered. Conclusions: The CT-P13 SC brings a new anti-TNF era. Achieving much higher drug levels that are constant over time opens new paths to explore the management of patients with IBD: less immunogenicity, better perianal disease control and higher achievement of mucosal healing. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

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12 pages, 1859 KiB

Open AccessArticle

Hemin Ameliorates the Inflammatory Activity in the Inflammatory Bowel Disease: A Non-Clinical Study in Rodents

by Inês Silva, Rita Correia, Rui Pinto and Vanessa Mateus

Biomedicines 2022, 10(8), 2025; https://doi.org/10.3390/biomedicines10082025 - 19 Aug 2022

Cited by 4 | Viewed by 1818

Abstract

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. Currently, there is no cure, and pharmacological treatment aims to induce and maintain remission in patients, so it is essential to investigate new possible treatments. Hemin is a heme-oxygenase [...] Read more.

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. Currently, there is no cure, and pharmacological treatment aims to induce and maintain remission in patients, so it is essential to investigate new possible treatments. Hemin is a heme-oxygenase inducer which can confer anti-inflammatory, cytoprotective, and antiapoptotic effects; therefore, it can be considered an asset for different gastrointestinal pathologies, namely for IBD. Aim: This experiment aims to evaluate the efficacy and safety of hemin, in a chronic 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model in rodents. Methods: The induction of chronic colitis consisted of five weekly intrarectal administrations of 1% TNBS. Then, the mice were treated daily with 5 mg/kg/day or 10 mg/kg/day of hemin, through intraperitoneal injections, for 14 days. Results: Hemin demonstrated an anti-inflammatory effect through the reduction in tumor necrosis factor (TNF)-α levels, fecal calprotectin, and fecal hemoglobin. It was also found to be safe in terms of extraintestinal manifestations, since hemin did not promote renal and/or hepatic changes. Conclusions: Hemin could become an interesting tool for new possible pharmacological approaches in the management of IBD. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

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9 pages, 425 KiB

Open AccessArticle

Adalimumab Biosimilar GP2017 versus Adalimumab Originator in Treating Patients with Inflammatory Bowel Diseases: A Real-Life, Multicenter, Observational Study

by Giammarco Mocci, Giorgia Bodini, Leonardo Allegretta, Alessia Immacolata Cazzato, Stefania Chiri, Giovanni Aragona, Patrizia Perazzo, Antonio Ferronato, Maria Giovanna Graziani, Cristiano Pagnini, Costantino Zampaletta, Camilla Graziosi, Marcello Picchio, Walter Elisei, Giovanni Maconi and Antonio Tursi

Biomedicines 2022, 10(8), 1799; https://doi.org/10.3390/biomedicines10081799 - 26 Jul 2022

Cited by 7 | Viewed by 2275

Abstract

The approval of adalimumab (ADA) biosimilars for inflammatory bowel disease (IBD) has reduced the cost of treatment. While several ADA biosimilars are currently available, comparative data on the ADA biosimilar GP2017 (Hyrimoz^TM) and its originator (Humira^TM) in IBD are [...] Read more.

The approval of adalimumab (ADA) biosimilars for inflammatory bowel disease (IBD) has reduced the cost of treatment. While several ADA biosimilars are currently available, comparative data on the ADA biosimilar GP2017 (Hyrimoz^TM) and its originator (Humira^TM) in IBD are lacking. We compared the efficacy and safety of GP2017 versus originator in IBD outpatients in an Italian real-life setting. This retrospective analysis enrolled consecutive IBD patients with complete clinical, laboratory, and endoscopic data. Clinical activity was assessed with the Mayo score in ulcerative colitis (UC) and the Harvey–Bradshaw Index in Crohn’s disease (CD). The primary endpoints were the induction of remission and the safety of GP2017 versus ADA originator. One hundred and thirty-four patients (30.6% with UC and 69.4% with CD, median age 38 years) were enrolled: 62 (46.3%) patients were treated with GP2017, and 72 (53.7%) with ADA originator; 118 (88.1%) patients were naïve to ADA. Clinical remission was obtained in 105 (78.4%) patients, during a median follow-up of 12 months, 82.3% and 75% in the GP2017 and ADA originator groups, respectively (p = 0.311). Treatment was well tolerated in both groups. This analysis of real-world data suggests that GP2017 and its originator are equivalent in terms of efficacy and safety in patients with IBD. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

10 pages, 596 KiB

Open AccessArticle

Impact of SARS-CoV-2 Infection on the Course of Inflammatory Bowel Disease in Patients Treated with Biological Therapeutic Agents: A Case-Control Study

by Alfredo Papa, Franco Scaldaferri, Marcello Covino, Antonio Tursi, Federica Furfaro, Giammarco Mocci, Loris Riccardo Lopetuso, Giovanni Maconi, Stefano Bibbò, Marcello Fiorani, Lucrezia Laterza, Irene Mignini, Daniele Napolitano, Laura Parisio, Marco Pizzoferrato, Giuseppe Privitera, Daniela Pugliese, Tommaso Schepis, Elisa Schiavoni, Carlo Romano Settanni, Lorenzo Maria Vetrone, Alessandro Armuzzi, Silvio Danese and Antonio Gasbarrini Show full author list Hide full author list

Biomedicines 2022, 10(4), 843; https://doi.org/10.3390/biomedicines10040843 - 3 Apr 2022

Cited by 8 | Viewed by 2388

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has raised concerns in patients with inflammatory bowel disease (IBD), not only due to consequences of coronavirus disease 2019 itself but also as a possible cause of IBD relapse. The main objective of this study [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has raised concerns in patients with inflammatory bowel disease (IBD), not only due to consequences of coronavirus disease 2019 itself but also as a possible cause of IBD relapse. The main objective of this study was to assess the role of SARS-CoV-2 in IBD clinical recurrence in a cohort of patients undergoing biological therapy. Second, we evaluated the difference in C-reactive protein (CRP) levels between the start and end of the follow-up period (ΔCRP) and the rate of biological therapy discontinuation. Patients with IBD positive for SARS-CoV-2 infection were compared with non-infected patients. IBD recurrence was defined as the need for intensification of current therapy. We enrolled 95 IBD patients with SARS-CoV-2 infection and 190 non-infected patients. During follow-up, 11 of 95 (11.6%) SARS-CoV-2-infected patients experienced disease recurrence compared to 21 of 190 (11.3%) in the control group (p = 0.894). Forty-six (48.4%) SARS-CoV-2-infected patients discontinued biological therapy versus seven (3.7%) in the control group (p < 0.01). In the multivariate analysis, biological agent discontinuation (p = 0.033) and ΔCRP (p = 0.017), but not SARS-CoV-2 infection (p = 0.298), were associated with IBD recurrence. SARS-CoV-2 infection was not associated with increased IBD recurrence rates in this cohort of patients treated with biological agents. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

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22 pages, 2178 KiB

Open AccessArticle

Cow Milk Extracellular Vesicle Effects on an In Vitro Model of Intestinal Inflammation

by Samanta Mecocci, Alessio Ottaviani, Elisabetta Razzuoli, Paola Fiorani, Daniele Pietrucci, Chiara Grazia De Ciucis, Silvia Dei Giudici, Giulia Franzoni, Giovanni Chillemi and Katia Cappelli

Biomedicines 2022, 10(3), 570; https://doi.org/10.3390/biomedicines10030570 - 28 Feb 2022

Cited by 22 | Viewed by 4437

Abstract

Extracellular vesicles (EVs) are lipid bilayer nano-dimensional spherical structures and act mainly as signaling mediators between cells, in particular modulating immunity and inflammation. Milk-derived EVs (mEVs) can have immunomodulatory and anti-inflammatory effects, and milk is one of the most promising food sources of [...] Read more.

Extracellular vesicles (EVs) are lipid bilayer nano-dimensional spherical structures and act mainly as signaling mediators between cells, in particular modulating immunity and inflammation. Milk-derived EVs (mEVs) can have immunomodulatory and anti-inflammatory effects, and milk is one of the most promising food sources of EVs. In this context, this study aimed to evaluate bovine mEVs anti-inflammatory and immunomodulating effects on an in vitro co-culture (Caco-2 and THP-1) model of intestinal inflammation through gene expression evaluation with RT-qPCR and cytokine release through ELISA. After establishing a pro-inflammatory environment due to IFN-γ and LPS stimuli, CXCL8, IL1B, TNFA, IL12A, IL23A, TGFB1, NOS2, and MMP9 were significantly up-regulated in inflamed Caco-2 compared to the basal co-culture. Moreover, IL-17, IL-1β, IL-6, TNF-α release was increased in supernatants of THP-1. The mEV administration partially restored initial conditions with an effective anti-inflammatory activity. Indeed, a decrease in gene expression and protein production of most of the tested cytokines was detected, together with a significant gene expression decrease in MMP9 and the up-regulation of MUC2 and TJP1. These results showed a fundamental capability of mEVs to modulate inflammation and their potential beneficial effect on the intestinal mucosa. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

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16 pages, 3139 KiB

Open AccessArticle

A Novel Role of Dapagliflozin in Mitigation of Acetic Acid-Induced Ulcerative Colitis by Modulation of Monocyte Chemoattractant Protein 1 (MCP-1)/Nuclear Factor-Kappa B (NF-κB)/Interleukin-18 (IL-18)

by Mohamed Kh. ElMahdy, Samar A. Antar, Ehab Kotb Elmahallawy, Walied Abdo, Hayfa Hussin Ali Hijazy, Ashraf Albrakati and Ahmed E. Khodir

Biomedicines 2022, 10(1), 40; https://doi.org/10.3390/biomedicines10010040 - 25 Dec 2021

Cited by 11 | Viewed by 3671

Abstract

Colon illnesses, particularly ulcerative colitis, are considered a major cause of death in both men and women around the world. The present study investigated the underlying molecular mechanisms for the potential anti-inflammatory effect of Dapagliflozin (DAPA) against ulcerative colitis (UC) induced by intracolonic [...] Read more.

Colon illnesses, particularly ulcerative colitis, are considered a major cause of death in both men and women around the world. The present study investigated the underlying molecular mechanisms for the potential anti-inflammatory effect of Dapagliflozin (DAPA) against ulcerative colitis (UC) induced by intracolonic instillation of 3% v/v acetic acid (AA). DAPA was administered to rats (1 mg/kg, orally) for two weeks during the treatment regimen. Interestingly, compared to the normal group, a marked increase in the index of colon/body weight, colon weight/colon length ratio, serum lactate dehydrogenase (LDH), and C-reactive protein (CRP), besides decrease in the serum total antioxidant capacity (TAC), were reported in the AA control group (p ˂ 0.05). Elevation in colon monocyte chemoattractant protein (MCP1), Interleukin 18 (IL-18), and inflammasome contents were also reported in the AA control group in comparison with the normal group. In addition, colon-specimen immunohistochemical staining revealed increased expression of nuclear factor-kappa B (NF-κB) and Caspase-3 with histopathological changes. Moreover, DAPA significantly (p ˂ 0.05) reduced the colon/body weight index, colon weight/colon length ratio, clinical evaluation, and macroscopic scoring of UC, and preserved the histopathological architecture of tissues. The inflammatory biomarkers, including colon MCP1, IL-18, inflammasome, Caspase-3, and NF-κB, were suppressed following DAPA treatment and oxidants/antioxidants hemostasis was also restored. Collectively, the present data demonstrate that DAPA represents an attractive approach to ameliorating ulcerative colitis through inhibiting MCP1/NF-κB/IL-18 pathways, thus preserving colon function. Antioxidant, anti-inflammatory, and anti-apoptotic properties of DAPA are implicated in its observed therapeutic benefits. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

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16 pages, 7323 KiB

Open AccessArticle

Inhibition of Prolyl Oligopeptidase Prevents Consequences of Reperfusion following Intestinal Ischemia

by Alessia Filippone, Giovanna Casili, Alessio Ardizzone, Marika Lanza, Deborah Mannino, Irene Paterniti, Emanuela Esposito and Michela Campolo

Biomedicines 2021, 9(10), 1354; https://doi.org/10.3390/biomedicines9101354 - 29 Sep 2021

Cited by 8 | Viewed by 2455

Abstract

Background: Intestinal ischemia/reperfusion injury (IRI) remains a clinical event that contributes to high morbidity and mortality rates. Intestinal epithelium is exposed to histological and vascular changes following tissue ischemia. Prolyl endopeptidase (PREP), involved in inflammatory responses, could be targeted for recovery from the [...] Read more.

Background: Intestinal ischemia/reperfusion injury (IRI) remains a clinical event that contributes to high morbidity and mortality rates. Intestinal epithelium is exposed to histological and vascular changes following tissue ischemia. Prolyl endopeptidase (PREP), involved in inflammatory responses, could be targeted for recovery from the permanent consequences following intestinal ischemia. Our aim was to investigate the role of PREP inhibitor KYP-2047 in tissue damage, angiogenesis, and endothelial barrier permeability after intestinal IRI in mice. Methods: KYP-2047 treatments were performed 5 min prior to intestinal damage. Intestinal IRI was induced in mice by clamping the superior mesenteric artery and the celiac trunk for 30 min, followed by 1 h of reperfusion. Results: PREP inhibition by KYP-2047 treatment reduced intestinal IR-induced histological damage and neutrophil accumulation, limiting inflammation through decrease of NF-ĸB nuclear translocation and fibrotic processes. KYP-2047 treatment restored barrier permeability and structural alteration following intestinal IRI, attenuating neovascular processes compromised by ischemia/reperfusion. Additionally, loss of epithelial cells during intestinal ischemia occurring by apoptosis was limited by KYP-2047 treatment, which showed strong effects counteracting apoptosis and DNA damage. Conclusions: These findings provide the first evidence that PREP inhibition through KYP-2047 inhibitor use could be a validate strategy for resolving alterations of intestinal epithelium the pathophysiology of intestinal disease. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

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Review

Jump to: Research, Other

13 pages, 632 KiB

Open AccessReview

Sphingosine 1-Phosphate Modulation in Inflammatory Bowel Diseases: Keeping Lymphocytes Out of the Intestine

by Arianna Dal Buono, Roberto Gabbiadini, Ludovico Alfarone, Virginia Solitano, Alessandro Repici, Stefania Vetrano, Antonino Spinelli and Alessandro Armuzzi

Biomedicines 2022, 10(7), 1735; https://doi.org/10.3390/biomedicines10071735 - 19 Jul 2022

Cited by 24 | Viewed by 3808

Abstract

Inflammatory bowel diseases (IBDs) are chronic and disabling conditions that, uncontrolled, lead to irreversible bowel damage and associated comorbidities. Despite the new era of biological therapies, IBDs remain not curative. The treatment purpose is to induce endoscopic remission, reduce the progression of the [...] Read more.

Inflammatory bowel diseases (IBDs) are chronic and disabling conditions that, uncontrolled, lead to irreversible bowel damage and associated comorbidities. Despite the new era of biological therapies, IBDs remain not curative. The treatment purpose is to induce endoscopic remission, reduce the progression of the disease and improve the quality of life. Optimal and early treatment could enable the prevention of their complications. Small molecules, administrated as oral agents, have the capacity of overcoming the limitations of biologic agents (i.e., parenteral administration, rapidity of action and primary and secondary non-responsiveness). Of special interest are results from the use of oral sphingosine 1-phosphate (S1P) receptor modulators (ozanimod, etrasimod, fingolimod and laquinimod), based on S1P activities to target lymphocyte recirculation in the mucosa, acting as immunosuppressive agents. Most S1P modulators are reported to be safe and effective in the treatment of both UC and CD. High and satisfactory rates of clinical remission as well as endoscopic improvement and remission can be achieved with these molecules. Safety alarms remain rather low, although the S1P binding to two of its G protein-coupled receptors, 2 and 3 (S1PR2 and S1PR3), may be associated with cardiovascular risks. Cost-effectiveness studies and head-to-head trials are needed to better define their place in therapy. This review summarizes these emerging data published by PubMed and EMBASE databases and from ongoing clinical trials on the safety and efficacy of selectivity of S1P modulators in the treatment of IBD. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

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16 pages, 1067 KiB

Open AccessEditor’s ChoiceReview

Health Benefits of Dietary Fiber for the Management of Inflammatory Bowel Disease

by Kafayat Yusuf, Subhrajit Saha and Shahid Umar

Biomedicines 2022, 10(6), 1242; https://doi.org/10.3390/biomedicines10061242 - 26 May 2022

Cited by 34 | Viewed by 17489

Abstract

Crohn’s disease (CD) and ulcerative colitis (UC), two components of inflammatory bowel disease (IBD), are painful conditions that affect children and adults. Despite substantial research, there is no permanent cure for IBD, and patients face an increased risk of colon cancer. Dietary fiber’s [...] Read more.

Crohn’s disease (CD) and ulcerative colitis (UC), two components of inflammatory bowel disease (IBD), are painful conditions that affect children and adults. Despite substantial research, there is no permanent cure for IBD, and patients face an increased risk of colon cancer. Dietary fiber’s health advantages have been thoroughly investigated, and it is recommended for its enormous health benefits. This review article discusses the importance of appropriate fiber intake in managing IBD, emphasizing how optimal fiber consumption can significantly help IBD patients. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

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19 pages, 328 KiB

Open AccessReview

Is There a Best First Line Biological/Small Molecule in IBD: Are We Ready for Sequencing?

by Gustavo Drügg Hahn, Petra Anna Golovics, Panu Wetwittayakhlang, Alex Al Khoury, Talat Bessissow and Peter Laszlo Lakatos

Biomedicines 2022, 10(4), 749; https://doi.org/10.3390/biomedicines10040749 - 23 Mar 2022

Cited by 6 | Viewed by 4433

Abstract

Inflammatory bowel disease (IBD) is a chronic, life-long inflammatory condition of the gastrointestinal tract. Treatment strategy depends on the severity of the disease course. IBD physicians need to be aware of the life-long treatment options available. The goal is not only to achieve [...] Read more.

Inflammatory bowel disease (IBD) is a chronic, life-long inflammatory condition of the gastrointestinal tract. Treatment strategy depends on the severity of the disease course. IBD physicians need to be aware of the life-long treatment options available. The goal is not only to achieve clinical remission but to halt or stabilize the chronic inflammation in the intestines to prevent further structural damage. Therefore, the use of early biologic therapy is recommended in moderate-to-severe IBD patients. However, in the last decade, use of therapeutic drug monitoring has increased considerably, opening an opportunity for sequencing. This review summarizes the available evidence on biologic and small molecules therapy in Crohn’s disease (CD) and ulcerative colitis (UC) in different clinical scenarios, including perianal CD, the elderly, extra intestinal manifestations, and pregnancy. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

45 pages, 448 KiB

Open AccessReview

Improving the Efficacy of Mesenchymal Stem/Stromal-Based Therapy for Treatment of Inflammatory Bowel Diseases

by Mercedes Lopez-Santalla and Marina Inmaculada Garin

Biomedicines 2021, 9(11), 1507; https://doi.org/10.3390/biomedicines9111507 - 20 Oct 2021

Cited by 16 | Viewed by 2699

Abstract

Inflammatory bowel diseases (IBD) consisting of persistent and relapsing inflammatory processes of the intestinal mucosa are caused by genetic, environmental, and commensal microbiota factors. Despite recent advances in clinical treatments aiming to decrease inflammation, nearly 30% of patients treated with biologicals experienced drawbacks [...] Read more.

Inflammatory bowel diseases (IBD) consisting of persistent and relapsing inflammatory processes of the intestinal mucosa are caused by genetic, environmental, and commensal microbiota factors. Despite recent advances in clinical treatments aiming to decrease inflammation, nearly 30% of patients treated with biologicals experienced drawbacks including loss of response, while others can develop severe side effects. Hence, novel effective treatments are highly needed. Mesenchymal stem/stromal cell (MSCs) therapy is an innovative therapeutic alternative currently under investigation for IBD. MSCs have the inherent capacity of modulating inflammatory immune responses as well as regenerating damaged tissues and are therefore a prime candidate to use as cell therapy in patients with IBD. At present, MSC-based therapy has been shown preclinically to modulate intestinal inflammation, whilst the safety of MSC-based therapy has been demonstrated in clinical trials. However, the successful results in preclinical studies have not been replicated in clinical trials. In this review, we will summarize the protocols used in preclinical and clinical trials and the novel approaches currently under investigation which aim to increase the beneficial effects of MSC-based therapy for IBD. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

12 pages, 583 KiB

Open AccessReview

The Revival of Surgery in Crohn’s Disease—Early Intestinal Resection as a Reasonable Alternative in Localized Ileitis

by Matthias Kelm, Christoph-Thomas Germer, Nicolas Schlegel and Sven Flemming

Biomedicines 2021, 9(10), 1317; https://doi.org/10.3390/biomedicines9101317 - 26 Sep 2021

Cited by 8 | Viewed by 4081

Abstract

Crohn’s disease (CD) represents a heterogeneous and complex disease with no curative therapeutic option available to date. Current therapy is mainly antibody-based focusing on the immune system while other treatment alternatives such as surgery are considered to be “last options”. However, medical therapy [...] Read more.

Crohn’s disease (CD) represents a heterogeneous and complex disease with no curative therapeutic option available to date. Current therapy is mainly antibody-based focusing on the immune system while other treatment alternatives such as surgery are considered to be “last options”. However, medical therapy for CD results in mild to severe side effects in a relevant amount of patients and some patients do not respond to the medication. Following that, quality of life is often significantly reduced in this patient cohort, thus, therapeutic alternatives are urgently needed. Updated evidence has revealed that surgery such as ileocecal resection (ICR) might be a potential therapeutic option in case of localized terminal ileitis since resection at early time points improves quality of life and significantly reduces the postoperative need for immunosuppressive medication with low rates of morbidity. In addition, new surgical approaches such as Kono-S anastomosis or inclusion of the mesentery result in significantly reduced rates of disease recurrence and reoperation. Based on the new evidence, the goal of this review is to provide an update on the role of surgery as a reasonable alternative to medical therapy in the interdisciplinary treatment of patients with CD. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

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12 pages, 3087 KiB

Open AccessReview

Adrenomedullin: A Novel Therapeutic for the Treatment of Inflammatory Bowel Disease

by Shinya Ashizuka, Toshihiro Kita, Haruhiko Inatsu and Kazuo Kitamura

Biomedicines 2021, 9(8), 1068; https://doi.org/10.3390/biomedicines9081068 - 23 Aug 2021

Cited by 20 | Viewed by 3237

Abstract

Adrenomedullin (AM) is a bioactive peptide with various physiological functions, including vasodilation, angiogenesis, anti-inflammation, organ protection, and tissue repair. AM suppresses inflammatory cytokine production in the intestinal mucosa, improves vascular and lymphatic regeneration and function, mucosal epithelial repair, and immune function in the [...] Read more.

Adrenomedullin (AM) is a bioactive peptide with various physiological functions, including vasodilation, angiogenesis, anti-inflammation, organ protection, and tissue repair. AM suppresses inflammatory cytokine production in the intestinal mucosa, improves vascular and lymphatic regeneration and function, mucosal epithelial repair, and immune function in the intestinal bacteria of animal models with intestinal inflammation. We have been promoting translational research to develop novel therapeutic agents for inflammatory bowel disease (IBD) using AM and have started clinical research for IBD patients since 2010. A multicenter clinical trial is currently underway in Japan for patients with refractory ulcerative colitis and Crohn’s disease. Moreover, since current AM administration is limited to continuous intravenous infusion, the development of a subcutaneous formulation using long-acting AM is underway for outpatient treatment. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

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17 pages, 2100 KiB

Open AccessSystematic Review

Cannabinoid Therapeutic Effects in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

by Antonio Vinci, Fabio Ingravalle, Dorian Bardhi, Nicola Cesaro, Sara Frassino, Francesca Licata and Marco Valvano

Biomedicines 2022, 10(10), 2439; https://doi.org/10.3390/biomedicines10102439 - 29 Sep 2022

Cited by 8 | Viewed by 3107

Abstract

(1) Introduction: Inflammatory Bowel Disease (IBD) patients may benefit from cannabinoid administration supplementary therapy; currently no consensus on its effect has been reached. (2) Methods: a systematic review of RCTs on cannabinoid supplementation therapy in IBD has been conducted; data sources were MEDLINE, [...] Read more.

(1) Introduction: Inflammatory Bowel Disease (IBD) patients may benefit from cannabinoid administration supplementary therapy; currently no consensus on its effect has been reached. (2) Methods: a systematic review of RCTs on cannabinoid supplementation therapy in IBD has been conducted; data sources were MEDLINE, Scopus, ClinicalTrials. (3) Results: out of 974 papers found with electronic search, six studies have been included into the systematic review, and five of them, for a grand total of 208 patients, were included into the meta-analysis. (4) Conclusions: cannabinoid supplementation as adjuvant therapy may increase the chances of success for standard therapy of Crohn’s Disease during the induction period; no statement on its potential usage during maintenance period can be derived from retrieved evidence. Its usage in Ulcerative Colitis is not to be recommended. If ever, low-dose treatment may be more effective than higher dosage. Mean CDAI reduction was found stronger in patients treated with cannabinoids (mean CDAI reduction = 36.63, CI 95% 12.27–61.19) than placebo. In future studies, it is advisable to include disease activity levels, as well as patient-level information such as genetic and behavioral patterns. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

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Open AccessSystematic Review

Pharmacogenetics of Biological Agents Used in Inflammatory Bowel Disease: A Systematic Review

by Rita Lauro, Federica Mannino, Natasha Irrera, Francesco Squadrito, Domenica Altavilla, Giovanni Squadrito, Giovanni Pallio and Alessandra Bitto

Biomedicines 2021, 9(12), 1748; https://doi.org/10.3390/biomedicines9121748 - 23 Nov 2021

Cited by 20 | Viewed by 2943

Abstract

Inflammatory Bowel Disease (IBD) comprises a group of disorders, in particular Crohn’s disease (CD) and ulcerative colitis (UC), characterized by chronic inflammation affecting the gastrointestinal tract. The treatment of these conditions is primarily based on anti-inflammatory drugs, although the use of biological drugs [...] Read more.

Inflammatory Bowel Disease (IBD) comprises a group of disorders, in particular Crohn’s disease (CD) and ulcerative colitis (UC), characterized by chronic inflammation affecting the gastrointestinal tract. The treatment of these conditions is primarily based on anti-inflammatory drugs, although the use of biological drugs with lower side effects quickly increased in the last decade. However, the presence of certain polymorphisms in the population may determine a different outcome in response to therapy, reflecting the heterogeneity of the efficacy in patients. Considering that several studies showed important correlations between genetic polymorphisms and response to biological treatments in IBD patients, this systematic review aims to summarize the pharmacogenetics of biologicals approved for IBD, thus highlighting a possible association between some polymorphisms and drug response. With this purpose, we reviewed PubMed papers published over the past 21 years (2000–2021), using as the search term “drug name and IBD or CD or UC and polymorphisms” to underline the role of pharmacogenetic tests in approaching the disease with a targeted therapy. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches in Inflammatory Bowel Diseases 2.0)

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