Gastrointestinal Disorders

Editorial

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4 pages, 210 KiB

Open AccessEditorial

Aspects of the Pathogenesis and Management of Inflammatory Bowel Diseases

by Andrew S. Day

Gastrointest. Disord. 2021, 3(3), 96-99; https://doi.org/10.3390/gidisord3030010 - 28 Jul 2021

Viewed by 2493

Abstract

Over the last two decades, inflammatory bowel disease (IBD) has been diagnosed more often in many countries around the world, including in parts of the world where IBD was previously uncommon [...] Full article

(This article belongs to the Special Issue Aspects of the Pathogenesis and Management of the Inflammatory Bowel Diseases)

Research

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6 pages, 385 KiB

Open AccessCommunication

by Laura Appleton and Andrew S. Day

Gastrointest. Disord. 2021, 3(1), 23-28; https://doi.org/10.3390/gidisord3010002 - 14 Jan 2021

Cited by 1 | Viewed by 3711

Abstract

Insufficient disease-related knowledge can be a barrier to the effective management of the unpredictable and lifelong course of inflammatory bowel disease (IBD). Patients with chronic illnesses have high non-adherence rates, with direct clinical consequences. While no single intervention strategy can improve the adherence [...] Read more.

Insufficient disease-related knowledge can be a barrier to the effective management of the unpredictable and lifelong course of inflammatory bowel disease (IBD). Patients with chronic illnesses have high non-adherence rates, with direct clinical consequences. While no single intervention strategy can improve the adherence of all patients, the success of attempts to improve patient adherence depends upon the realistic assessment of patients’ knowledge and their understanding of the regimen. The aim of this study was to assess the disease-specific knowledge of the parents and patients with IBD in the South Island of New Zealand, and identify areas of poor knowledge. Families of children diagnosed with IBD were asked to complete the IBD Knowledge Inventory Device (IBD-KID). Patients 10 years and older were asked to participate along with their parents. Of 110 families, 91 responded, with completed questionnaires received from 153 parents and 66 patients. Overall, parents scored significantly higher (13.64 ± 3.88) than their children (10.03 ± 4.07; p < 0.001). Areas of poor knowledge included aspects of treatment (both conventional and alternative), along with long-term disease outcomes. This study has shown clear areas of concern in this population’s disease-specific knowledge of their disease. This should be addressed through targeted education for both the patient and the parents to improve not only their knowledge, but also their adherence and disease self-management. Full article

(This article belongs to the Special Issue Aspects of the Pathogenesis and Management of the Inflammatory Bowel Diseases)

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12 pages, 2957 KiB

Open AccessArticle

20 kDa PEGylated Adrenomedullin as a New Therapeutic Candidate for Inflammatory Bowel Disease

by Goro Miki, Nobuko Kuroishi, Mariko Tokashiki, Sayaka Nagata, Masaji Tamura, Taku Yoshiya, Kumiko Yoshizawa-Kumagaye, Shinya Ashizuka, Joji Kato, Motoo Yamasaki and Kazuo Kitamura

Gastrointest. Disord. 2020, 2(4), 366-377; https://doi.org/10.3390/gidisord2040033 - 7 Oct 2020

Cited by 2 | Viewed by 3376

Abstract

Human adrenomedullin (AM), a hypotensive peptide, also has anti-colitis activity. We prepared a polyethylene glycol (PEG) ylated form of AM through the conjugation of PEG-AM (1–15) and AM (15–52). Highly pure monomeric 20 kDa PEG-AM (20kPEG-AM) stimulated cyclic adenosine monophosphate production in HEK-293 [...] Read more.

Human adrenomedullin (AM), a hypotensive peptide, also has anti-colitis activity. We prepared a polyethylene glycol (PEG) ylated form of AM through the conjugation of PEG-AM (1–15) and AM (15–52). Highly pure monomeric 20 kDa PEG-AM (20kPEG-AM) stimulated cyclic adenosine monophosphate production in HEK-293 cells stably expressing the type 1 AM receptor in a dose-dependent manner. The half-life of 20kPEG-AM was 7.4 h following subcutaneous administration in mice. We assessed the anti-colitis effect of subcutaneous 20kPEG-AM administration in the dextran sodium sulfate murine colitis model. Single and double subcutaneous injection of 20kPEG-AM significantly reduced total inflammation scores. These results suggest that 20kPEG-AM is a promising therapeutic candidate for the treatment of human inflammatory bowel diseases. Full article

(This article belongs to the Special Issue Aspects of the Pathogenesis and Management of the Inflammatory Bowel Diseases)

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7 pages, 519 KiB

Open AccessArticle

Associations between the Presence of Granulomata and Disease Phenotype and Outcomes in Children Diagnosed with Crohn’s Disease

by Laura Appleton, Euan Watt, Fiona Jagger, Richard Hansen, Richard B. Gearry and Andrew S. Day

Gastrointest. Disord. 2020, 2(2), 164-170; https://doi.org/10.3390/gidisord2020017 - 13 Jun 2020

Cited by 1 | Viewed by 2561

Abstract

Background: The finding of a mucosal granuloma on histological analysis of endoscopically obtained biopsies in children with Crohn’s disease has been suggested to provide prognostic information. The aim of this study was to retrospectively assess the rate of granuloma detection and the impact [...] Read more.

Background: The finding of a mucosal granuloma on histological analysis of endoscopically obtained biopsies in children with Crohn’s disease has been suggested to provide prognostic information. The aim of this study was to retrospectively assess the rate of granuloma detection and the impact of this upon specific disease characteristics and outcomes in children diagnosed with Crohn’s disease. After identification of a group of children previously diagnosed with Crohn’s disease, chart reviews were undertaken to characterise the children as granuloma positive or negative. Disease characteristics at diagnosis (such as disease location and nutritional status) and following diagnosis (such as requirement for immunosuppressive medications and surgical intervention) were noted for each patient. Results: Ninety-four children from two distinct geographical areas were identified. Forty-nine (52.1%) of the children had mucosal granulomata. Children with colonic disease were likely to have granulomata detected (RR = 3.04; p < 0.001). Granulomata were associated with lower weight z-scores at diagnosis (p < 0.05), but not other disease features (e.g., perianal disease or extra-intestinal manifestations). The presence of a granuloma at diagnosis was also associated with increased rates of the subsequent requirement for an immunosuppressive medication (RR = 1.26; p = 0.002). The presence of granulomata on histological assessment of mucosal biopsies at diagnosis of children with Crohn’s disease appears to be associated with specific disease features and outcomes. These findings should be clarified prospectively in a larger cohort of children with Crohn’s disease. Full article

(This article belongs to the Special Issue Aspects of the Pathogenesis and Management of the Inflammatory Bowel Diseases)

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8 pages, 228 KiB

Open AccessCommunication

Apparent Disparities in Hospital Admission and Biologic Use in the Management of Inflammatory Bowel Disease between 2014–2018 in Some Black and Ethnic Minority (BEM) Populations in England

by Affifa Farrukh and John Mayberry

Gastrointest. Disord. 2020, 2(2), 144-151; https://doi.org/10.3390/gidisord2020015 - 29 May 2020

Cited by 8 | Viewed by 2498 | Correction

Abstract

Discrimination in delivery of care to patients with inflammatory bowel disease has been reported in the UK with regards to the South Asian population. This paper explores whether it is also true for Afro-Caribbean and Eastern European migrant workers. Treatment was investigated in [...] Read more.

Discrimination in delivery of care to patients with inflammatory bowel disease has been reported in the UK with regards to the South Asian population. This paper explores whether it is also true for Afro-Caribbean and Eastern European migrant workers. Treatment was investigated in NHS trusts, which served substantial migrant and minority communities, through Freedom of Information requests for data on use of biologics or hospital admissions over a five year period. In Bristol, Nottingham, Derby and Burton, Princess Alexandra Hospital Trust in Harlow, Essex and Kings College Hospital NHS Foundation Trust in South London Afro-Caribbean patients were treated significantly less often than White British patients. Eastern European migrant workers, were admitted significantly less often in Croydon, and the Princess Alexandra Hospital NHS Trust in Essex. However, there was no evidence of barriers to access for these communities in Wye Valley Trust, University Hospitals of Bristol NHS Foundation Trust or Queen Elizabeth Hospital Kings Lynn. In North West Anglia both South Asian and Eastern European patients were significantly less likely to be admitted to hospital than members of the White British community. It is incumbent on all gastroenterologists to consider their own clinical practice and encourage their hospital units to adopt effective policies which remove discriminatory barriers to good quality care. Full article

(This article belongs to the Special Issue Aspects of the Pathogenesis and Management of the Inflammatory Bowel Diseases)

10 pages, 979 KiB

Open AccessArticle

Quality of Life and Eligibility for Specific Financial Assistance for Medical Expenses: A Cross-Sectional Web-Based Survey among Patients with Inflammatory Bowel Disease in Japan

by Huyen Thi Thanh Tran, Shota Saito, Shinichi Noto and Kenji Suzuki

Gastrointest. Disord. 2020, 2(2), 123-133; https://doi.org/10.3390/gidisord2020012 - 3 May 2020

Cited by 1 | Viewed by 2859

Abstract

Specific financial assistance for people with rare and intractable diseases is part of Japan’s public health system. This survey aimed to clarify the relationship between eligibility for this specific financial assistance and quality of life (QOL) among individuals with inflammatory bowel disease (IBD) [...] Read more.

Specific financial assistance for people with rare and intractable diseases is part of Japan’s public health system. This survey aimed to clarify the relationship between eligibility for this specific financial assistance and quality of life (QOL) among individuals with inflammatory bowel disease (IBD) in Japan. A nationwide, web-based survey was conducted in Japan among 300 people with IBD. Questionnaire items covered socioeconomic characteristics and QOL, assessed with the five-dimension, five-level EuroQol (EQ-5D-5L). The percentage of respondents who were ineligible for specific financial assistance was 11.0% among those with Crohn’s disease (CD) and 34.0% among those with ulcerative colitis (UC). For those with CD, the median EQ-5D-5L utility weight did not differ significantly between the non-assistance and assistance groups (p = 0.2222). For those with UC, the median EQ-5D-5L utility weight was significantly higher in the non-assistance group than in the assistance group (p = 0.0034). The present study demonstrated that the revision of the law on intractable and rare diseases has not had a negative influence on the QOL of patients with IBD in Japan. Based on our findings, further research on patient-reported outcomes among individuals with IBD may be necessary to inform health policy makers. Full article

(This article belongs to the Special Issue Aspects of the Pathogenesis and Management of the Inflammatory Bowel Diseases)

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Review

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17 pages, 663 KiB

Open AccessReview

Overview of Self-Management Skills and Associated Assessment Tools for Children with Inflammatory Bowel Disease

by Angharad Vernon-Roberts, Richard B. Gearry and Andrew S. Day

Gastrointest. Disord. 2021, 3(2), 61-77; https://doi.org/10.3390/gidisord3020007 - 30 Mar 2021

Cited by 3 | Viewed by 4869

Abstract

Self-management is a multi-modal approach for managing chronic conditions that encompasses a number of different elements; knowledge, adherence, self-regulation, communication, and cognitive factors. Self-management has been shown to be beneficial for adults with inflammatory bowel disease (IBD), and for children with IBD it [...] Read more.

Self-management is a multi-modal approach for managing chronic conditions that encompasses a number of different elements; knowledge, adherence, self-regulation, communication, and cognitive factors. Self-management has been shown to be beneficial for adults with inflammatory bowel disease (IBD), and for children with IBD it may help them learn to take control of their complex treatment regimens and lead to positive disease outcomes. The development of self-management skills for children with IBD is vital in order to maximize their potential for health autonomy, but it is still an emergent field in this population. This review provides an over-arching view of the self-management elements specific to children with IBD, and highlights outcome measures that may be used to assess skills within each field as well as the efficacy of targeted interventions. Full article

(This article belongs to the Special Issue Aspects of the Pathogenesis and Management of the Inflammatory Bowel Diseases)

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13 pages, 1307 KiB

Open AccessReview

Unfolded Protein Response and Crohn’s Diseases: A Molecular Mechanism of Wound Healing in the Gut

by Chao Li

Gastrointest. Disord. 2021, 3(1), 31-43; https://doi.org/10.3390/gidisord3010004 - 10 Feb 2021

Cited by 4 | Viewed by 4262

Abstract

Endoplasmic reticulum (ER) stress triggers a series of signaling and transcriptional events termed the unfolded protein response (UPR). Severe ER stress is associated with the development of fibrosis in different organs, including lung, liver, kidney, heart, and intestine. ER stress is an essential [...] Read more.

Endoplasmic reticulum (ER) stress triggers a series of signaling and transcriptional events termed the unfolded protein response (UPR). Severe ER stress is associated with the development of fibrosis in different organs, including lung, liver, kidney, heart, and intestine. ER stress is an essential response of epithelial and immune cells in the pathogenesis of Inflammatory Bowel Disease (IBD), including Crohn’s disease (CD). Intestinal epithelial cells are susceptible to ER stress-mediated damage due to secretion of a large amount of proteins that are involved in mucosal defense. In other cells, ER stress is linked to myofibroblast activation, extracellular matrix production, macrophage polarization, and immune cell differentiation. This review focuses on the role of the UPR in the pathogenesis in IBD from an immunologic perspective. The roles of macrophage and mesenchymal cells in the UPR from in vitro and in vivo animal models are discussed. The links between ER stress and other signaling pathways, such as senescence and autophagy, are introduced. Recent advances in the understanding of the epigenetic regulation of the UPR signaling are also updated here. The future directions of development of the UPR research and therapeutic strategies to manipulate ER stress levels are also reviewed. Full article

(This article belongs to the Special Issue Aspects of the Pathogenesis and Management of the Inflammatory Bowel Diseases)

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13 pages, 311 KiB

Open AccessReview

Making Decisions about Dietary Therapy in Inflammatory Bowel Disease

by Sydney Solomon, Eunie Park and Joseph A. Picoraro

Gastrointest. Disord. 2020, 2(4), 353-365; https://doi.org/10.3390/gidisord2040032 - 7 Oct 2020

Cited by 1 | Viewed by 3581

Abstract

Treatment for inflammatory bowel disease (IBD) deserves an informed shared decision-making process between patient and doctor. IBD spans a spectrum of phenotypes that impact each patient uniquely. While treatment has primarily consisted of medical or surgical therapy, dietary approaches have become increasingly relevant. [...] Read more.

Treatment for inflammatory bowel disease (IBD) deserves an informed shared decision-making process between patient and doctor. IBD spans a spectrum of phenotypes that impact each patient uniquely. While treatment has primarily consisted of medical or surgical therapy, dietary approaches have become increasingly relevant. A majority of patients with IBD use some form of dietary modification, and it is common for patients to do this without their physicians’ knowledge. Lack of medical supervision can lead to nutritional deficiencies and a worsening disease state. Some patients work with their medical team to pursue a well-defined exclusion diet as a primary therapy, such as the specific carbohydrate diet, exclusive enteral nutrition, or the Crohn’s disease exclusion diet. The motivations to use dietary therapy for IBD remain unclear and the effectiveness has not been definitively established for many approaches. It is necessary for medical providers to be knowledgeable and to foster open communication with their patients in order to ensure the highest likelihood of remission. This review provides an overview of dietary treatment options, the current knowledge about patient motivations for pursuing dietary therapy, and the roles of patient empowerment and patient activation. We outline areas of improvement for the decision-making process. Full article

(This article belongs to the Special Issue Aspects of the Pathogenesis and Management of the Inflammatory Bowel Diseases)

21 pages, 2936 KiB

Open AccessReview

Intestinal Immune Homeostasis and Inflammatory Bowel Disease: A Perspective on Intracellular Response Mechanisms

by Kishu Ranjan

Gastrointest. Disord. 2020, 2(3), 246-266; https://doi.org/10.3390/gidisord2030024 - 22 Aug 2020

Cited by 4 | Viewed by 4942

Abstract

The pathogenesis of inflammatory bowel disease (IBD) involves perturbation of intestinal immune homeostasis in genetically susceptible individuals. A mutual interplay between intestinal epithelial cells (IECs) and gut resident microbes maintains a homeostatic environment across the gut. An idiopathic gastrointestinal (GI) complication triggers aberrant [...] Read more.

The pathogenesis of inflammatory bowel disease (IBD) involves perturbation of intestinal immune homeostasis in genetically susceptible individuals. A mutual interplay between intestinal epithelial cells (IECs) and gut resident microbes maintains a homeostatic environment across the gut. An idiopathic gastrointestinal (GI) complication triggers aberrant physiological stress in the epithelium and peripheral myeloid cells, leading to a chronic inflammatory condition. Indeed, events in the endoplasmic reticulum (ER) and mitochondria contribute to orchestrating intracellular mechanisms such as the unfolded protein response (UPR) and oxidative stress, respectively, to resolve aberrant cellular stress. This review highlights the signaling cascades encrypted within ER and mitochondria in IECs and/or myeloid cells to dissipate chronic stress in maintaining intestinal homeostasis. Full article

(This article belongs to the Special Issue Aspects of the Pathogenesis and Management of the Inflammatory Bowel Diseases)

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18 pages, 359 KiB

Open AccessReview

Vaccination in Inflammatory Bowel Disease: Utility and Future Perspective

by Giovanni Casella, Fabio Ingravalle, Adriana Ingravalle, Claudio Monti, Fulvio Bonetti, Federica De Salvatore, Vincenzo Villanacci and Aurelio Limonta

Gastrointest. Disord. 2020, 2(2), 175-192; https://doi.org/10.3390/gidisord2020019 - 23 Jun 2020

Cited by 2 | Viewed by 3301

Abstract

Inflammatory bowel disease (IBD) is an immune-mediated disease, which often require lifetime treatment with immunomodulators and immunosuppressive drugs. Both IBD and its treatments are associated with an increased risk of infectious disease and mortality. Several of these diseases are vaccine preventable and could [...] Read more.

Inflammatory bowel disease (IBD) is an immune-mediated disease, which often require lifetime treatment with immunomodulators and immunosuppressive drugs. Both IBD and its treatments are associated with an increased risk of infectious disease and mortality. Several of these diseases are vaccine preventable and could be avoided, reducing morbidity and mortality. However, vaccination rates among patients with IBD are lower than in the general population and both patients and doctors are not fully aware of the problem. Education campaigns and well planned vaccination schemes are necessary to improve vaccination coverage in patients with IBD. Immunomodulators and immunosuppressive drugs may reduce the seroprotection levels. For this reason, new vaccination schemes are being studied in patients with IBD. It is therefore important to understand which and when vaccines can be administrated based on immunocompetence or immunosuppression of patients. Usually, live-attenuated vaccines should be avoided in immunosuppressed patients, so assessing vaccination status and planning vaccination before immunosuppressive treatments are pivotal to reduce infection risk. The aim of this review is to increase the awareness of the problem and provide a quick reference for vaccination plan tailoring, especially for gastroenterologists and primary care physicians, who have the skills and knowledge to implement vaccination strategies. Full article

(This article belongs to the Special Issue Aspects of the Pathogenesis and Management of the Inflammatory Bowel Diseases)

10 pages, 249 KiB

Open AccessReview

The Role of Vitamin D in the Pathogenesis of Inflammatory Bowel Disease

by Stefano Nobile, Michela A. Tenace and Helen M. Pappa

Gastrointest. Disord. 2019, 1(1), 231-240; https://doi.org/10.3390/gidisord1010018 - 5 Mar 2019

Cited by 7 | Viewed by 4540

Abstract

Vitamin D has a complex role in the pathogenesis of inflammatory bowel disease (IBD), which is still under investigation. We conducted a literature search using PubMed through December 2018 through the use of relevant search terms. We found an abundance of evidence to [...] Read more.

Vitamin D has a complex role in the pathogenesis of inflammatory bowel disease (IBD), which is still under investigation. We conducted a literature search using PubMed through December 2018 through the use of relevant search terms. We found an abundance of evidence to support the role of vitamin D in regulating the innate and adaptive arms of the immune system. The pathogenesis of IBD implicates the immune dysregulation of these immune system components. Proof of concept of the vitamin’s role in the pathogenesis of IBD is the mapping of the vitamin D receptor in a region of chromosome 12, where IBD is also mapped, and specific VDR polymorphisms’ link to IBD phenotypes. Further research is needed to better delineate vitamin D’s role in preventing IBD and its potential as a therapeutic target for this disease. Full article

(This article belongs to the Special Issue The Interplay between Genetic Risk Factors, the Intestinal Microbiota, the Environment and Immune Responses in the Pathogenesis of IBD)

18 pages, 1554 KiB

Open AccessReview

Pathogenesis of Inflammatory Bowel Disease: Basic Science in the Light of Real-World Epidemiology

by Davide Giuseppe Ribaldone, Rinaldo Pellicano and Giovanni C. Actis

Gastrointest. Disord. 2019, 1(1), 129-146; https://doi.org/10.3390/gidisord1010010 - 12 Nov 2018

Cited by 8 | Viewed by 6018

Abstract

Major advances in the last few decades have favored the view of inflammatory bowel disease (IBD) as a disease of hyper- or, more often, paradoxical hyporesponsiveness of the gut-associated immune system. The relevant pivot seems to be the loss of the balance between [...] Read more.

Major advances in the last few decades have favored the view of inflammatory bowel disease (IBD) as a disease of hyper- or, more often, paradoxical hyporesponsiveness of the gut-associated immune system. The relevant pivot seems to be the loss of the balance between gut-associated pro-inflammatory lymphocytes and the indwelling microbiome species, with inner regulatory circuits (regulatory T-lymphocytes, T-reg) and outer factors (such as drugs, tobacco, diet components) contributing to complicate the matter. Light might be shed by the observation of the real-world IBD epidemiology, which may help unveil the factors that tend to cluster IBD cases to certain geographical areas. A transitional mind frame between bench and real-world gastroenterology could hopefully contribute to restrain the mounting epidemic of IBD in the Western world and to halt the more recent increases seen in many Eastern countries. Full article

(This article belongs to the Special Issue The Interplay between Genetic Risk Factors, the Intestinal Microbiota, the Environment and Immune Responses in the Pathogenesis of IBD)

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31 pages, 2289 KiB

Open AccessReview

The Multifactorial Etiopathogeneses Interplay of Inflammatory Bowel Disease: An Overview

by Amosy E. M’Koma

Gastrointest. Disord. 2019, 1(1), 75-105; https://doi.org/10.3390/gidisord1010007 - 18 Oct 2018

Cited by 13 | Viewed by 7752

Abstract

The gastrointestinal system where inflammatory bowel disease occurs is central to the immune system where the innate and the adaptive/acquired immune systems are balanced in interactions with gut microbes under homeostasis conditions. This article overviews the high-throughput research screening on multifactorial interplay between [...] Read more.

The gastrointestinal system where inflammatory bowel disease occurs is central to the immune system where the innate and the adaptive/acquired immune systems are balanced in interactions with gut microbes under homeostasis conditions. This article overviews the high-throughput research screening on multifactorial interplay between genetic risk factors, the intestinal microbiota, urbanization, modernization, Westernization, the environmental influences and immune responses in the etiopathogenesis of inflammatory bowel disease in humans. Inflammatory bowel disease is an expensive multifactorial debilitating disease that affects thousands new people annually worldwide with no known etiology or cure. The conservative therapeutics focus on the established pathology where the immune dysfunction and gut injury have already happened but do not preclude or delay the progression. Inflammatory bowel disease is evolving globally and has become a global emergence disease. It is largely known to be a disease in industrial-urbanized societies attributed to modernization and Westernized lifestyle associated with environmental factors to genetically susceptible individuals with determined failure to process certain commensal antigens. In the developing nations, increasing incidence and prevalence of inflammatory bowel disease (IBD) has been associated with rapid urbanization, modernization and Westernization of the population. In summary, there are identified multiple associations to host exposures potentiating the landscape risk hazards of inflammatory bowel disease trigger, that include: Western life-style and diet, host genetics, altered innate and/or acquired/adaptive host immune responses, early-life microbiota exposure, change in microbiome symbiotic relationship (dysbiosis/dysbacteriosis), pollution, changing hygiene status, socioeconomic status and several other environmental factors have long-standing effects/influence tolerance. The ongoing multipronged robotic studies on gut microbiota composition disparate patterns between the rural vs. urban locations may help elucidate and better understand the contribution of microbiome disciplines/ecology and evolutionary biology in potentially protecting against the development of inflammatory bowel disease. Full article

(This article belongs to the Special Issue The Interplay between Genetic Risk Factors, the Intestinal Microbiota, the Environment and Immune Responses in the Pathogenesis of IBD)

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18 pages, 869 KiB

Open AccessReview

CCR6–CCL20 Axis in IBD: What Have We Learnt in the Last 20 Years?

by Ranmali Ranasinghe and Rajaraman Eri

Gastrointest. Disord. 2019, 1(1), 57-74; https://doi.org/10.3390/gidisord1010006 - 15 Oct 2018

Cited by 9 | Viewed by 4970

Abstract

CC chemokine receptor 6 (CCR6) and its specific partner CC chemokine ligand 20 (CCL20) are known to play a pivotal role in intestinal inflammation. CCR6-associated inflammatory bowel disease (IBD) is already at the forefront of experimental inflammatory disease models, being the subject of [...] Read more.

CC chemokine receptor 6 (CCR6) and its specific partner CC chemokine ligand 20 (CCL20) are known to play a pivotal role in intestinal inflammation. CCR6-associated inflammatory bowel disease (IBD) is already at the forefront of experimental inflammatory disease models, being the subject of numerous analytical studies. IBD is associated with two sub phenotypes, Crohn’s disease (CD) and ulcerative colitis (UC). Both these disease entities produce potent immune dysregulation followed by intense tissue damage within the gut mucosal system, initiating symptoms that are severely debilitating. Multiple causative factors are said to be responsible for IBD, but direct immune dysfunction is kindled by overplay of innate and adaptive immune responses produced against the luminal contents through the weakened or leaky gut epithelial barrier. Once immune homeostasis is not achieved by endogenous protective mechanisms, the self-assertive adaptive immunity mobilizes its various T and B cell cohorts, initializing their immune mechanisms by deploying the immune cells towards the site of infection. CCR6 and its unique solitary ligand CCL20 are small protein molecules that are abundantly expressed by T and B lymphocytes and act as chemotactic immune-modulatory envoys that help in the deployment of the effector lymphocyte arm of the immune system and produce two directly opposing outcomes in IBD. This dichotomous immunity consists of either immune tolerance or inflammation which then develops into a chronic state, remaining unresponsive to inherent immunity or targeted clinical therapy. In this review, we have identified large numbers of experimental studies that have employed both mouse models and clinical subjects spanning a period of nearly two decades and we have clustered these into 13 different groups. This review will provide greater understanding of the CCR6–CCL20 axis in IBD and identify gaps in the literature that can be filled in the future. Full article

(This article belongs to the Special Issue The Interplay between Genetic Risk Factors, the Intestinal Microbiota, the Environment and Immune Responses in the Pathogenesis of IBD)

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18 pages, 932 KiB

Open AccessReview

Regulation of Antimicrobial Pathways by Endogenous Heat Shock Proteins in Gastrointestinal Disorders

by Emma Finlayson-Trick, Jessica Connors, Andrew Stadnyk and Johan Van Limbergen

Gastrointest. Disord. 2019, 1(1), 39-56; https://doi.org/10.3390/gidisord1010005 - 28 Sep 2018

Cited by 7 | Viewed by 4689

Abstract

Heat shock proteins (HSPs) are essential mediators of cellular homeostasis by maintaining protein functionality and stability, and activating appropriate immune cells. HSP activity is influenced by a variety of factors including diet, microbial stimuli, environment and host immunity. The overexpression and down-regulation of [...] Read more.

Heat shock proteins (HSPs) are essential mediators of cellular homeostasis by maintaining protein functionality and stability, and activating appropriate immune cells. HSP activity is influenced by a variety of factors including diet, microbial stimuli, environment and host immunity. The overexpression and down-regulation of HSPs is associated with various disease phenotypes, including the inflammatory bowel diseases (IBD) such as Crohn’s disease (CD). While the precise etiology of CD remains unclear, many of the putative triggers also influence HSP activity. The development of different CD phenotypes therefore may be a result of the disease-modifying behavior of the environmentally-regulated HSPs. Understanding the role of bacterial and endogenous HSPs in host homeostasis and disease will help elucidate the complex interplay of factors. Furthermore, discerning the function of HSPs in CD may lead to therapeutic developments that better reflect and respond to the gut environment. Full article

(This article belongs to the Special Issue The Interplay between Genetic Risk Factors, the Intestinal Microbiota, the Environment and Immune Responses in the Pathogenesis of IBD)

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15 pages, 756 KiB

Open AccessReview

CCR6–CCL20-Mediated Immunologic Pathways in Inflammatory Bowel Disease

by Ranmali Ranasinghe and Rajaraman Eri

Gastrointest. Disord. 2019, 1(1), 15-29; https://doi.org/10.3390/gidisord1010003 - 21 Aug 2018

Cited by 7 | Viewed by 5881

Abstract

Inflammatory bowel disease (IBD) has evoked significant interest in human immunobiology given its tactical immune evasion methodologies resulting in acute immune destabilization. IBD comprising Crohn’s disease and Ulcerative colitis manifests as chronic inflammation in the gut mucosa, leading to complexities involving immune dysregulation [...] Read more.

Inflammatory bowel disease (IBD) has evoked significant interest in human immunobiology given its tactical immune evasion methodologies resulting in acute immune destabilization. IBD comprising Crohn’s disease and Ulcerative colitis manifests as chronic inflammation in the gut mucosa, leading to complexities involving immune dysregulation in the T helper lymphocyte arm, effecting disease pathogenicity. The mucosa of the alimentary canal is constantly exposed to a myriad of food antigens and luminal microorganisms for which a consistent host-protective mechanism is operative in healthy people. Lowered mucosal immune expression which allows penetration of the epithelial barrier by infective pathogenic microbes elicits both innate and adaptive immune responses in the gut, culminating in aberrant intestinal inflammation. Interestingly, the IBD leukocyte repertoire is significantly entwined with chemokine-assisted chemotactic navigation into the sites of inflammation, which is also thought to generate favorable immune-suppressive responses. The functions of the cognate chemokine receptor, CCR6, which binds with its unique ligand CCL20, are expected to tilt the balance between upregulation of homeostatic tolerance and inflammatory pathophysiology. This review aims to critically examine the CCR6-driven immune pathways: T_H1/T_H2, T_H1/T_H17, T_H17/T_reg, IL-23/IL-17, Akt/ERK-1/2, ILC3, and T_H9/T_H2 for systematic investigation of its underlying mechanisms in the future and to underpin its importance in resolving IBD pathology. Thus, CCR6 occupies an exclusive position in gut immunology which renders it an invaluable therapeutic tool for the production of novel medicaments to treat IBD. Full article

(This article belongs to the Special Issue The Interplay between Genetic Risk Factors, the Intestinal Microbiota, the Environment and Immune Responses in the Pathogenesis of IBD)

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