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1
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Gerasimidis K. Nutrition and dietary therapy in paediatric inflammatory bowel disease. Clin Nutr ESPEN 2025; 67:233-241. [PMID: 40064235 DOI: 10.1016/j.clnesp.2025.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 03/03/2025] [Accepted: 03/04/2025] [Indexed: 03/29/2025]
Affiliation(s)
- Konstantinos Gerasimidis
- Human Nutrition, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, G31 2ER, Glasgow, UK.
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2
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Papathanasiou E, Kokkotis G, Axiaris G, Bellou G, Chalakatevaki K, Christidou A, Christodoulou DK, Foteinogiannopoulou K, Gatopoulou A, Giouleme O, Gkoumas K, Κalogirou M, Karatzas P, Κarmiris K, Κatsanos K, Κourikou A, Κoutroubakis IE, Liatsos C, Mantzaris GJ, Μathou N, Michalopoulos G, Μantaka A, Nikolaou P, Oikonomou M, Papatheodoridis G, Polymeros D, Skouloudis E, Soufleris K, Stergiou E, Theodoulou A, Theodoropoulou A, Theoxaris G, Tsafaraki S, Tsiolakidou G, Tsironi E, Tzouvala M, Viazis N, Michopoulos S, Bamias G, Zampeli E. Pregnancy outcomes in Greek women with inflammatory bowel disease: a longitudinal national retrospective study. Eur J Gastroenterol Hepatol 2025; 37:154-160. [PMID: 39324945 DOI: 10.1097/meg.0000000000002844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/27/2024]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) commonly affects patients of reproductive age. The effect of disease activity on the outcome of pregnancy and its impact on neonatal health are areas of intense research. METHODS Α national retrospective study of pregnancies in women with IBD between 2010 and 2020 was carried out in 22 IBD reference centers in Greece. RESULTS IN TOTAL 223 pregnancies in 175 IBD patients [122 Crohn's disease (CD)] were included. Mean age at diagnosis was 26 years (12-44) with a mean duration of 7.4 (0-23). Pregnancy as a result of IVF occurred in 15 cases (6.7%). At the beginning of gestation, 165 patients (74%) were under treatment: 48 (29%) with anti-tumor necrosis factor alpha agents, 43 (26%) with azathioprine, 101 (61%) with 5-aminosalicylates, and 12 (7%) with steroids. Forty-nine cases (22%) of IBD flares were recorded: Two-thirds ( n = 30) were in clinical remission at the onset of pregnancy, whereas treatment with corticosteroids was required in 22 (45%). Patients with ulcerative colitis were at greater risk for flare compared to those with CD ( P < 0.001). All but two pregnancies (99.1%) resulted in an uncomplicated delivery. In 147 cases (67.1%), c-section was performed. Two late fetal deaths (0.9%) were reported, both in patients with persistently active disease. After delivery, 75 patients (34%) presented with a disease flare, associated with active disease at the beginning of pregnancy ( P < 0.001). CONCLUSION The majority of Greek patients with IBD have a favorable pregnancy outcome. Active inflammation during gestation and a diagnosis of ulcerative colitis are negatively associated with pregnancy outcomes.
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Affiliation(s)
| | - Georgios Kokkotis
- 3rd Academic Department of Internal Medicine University of Athens, Sotiria General Hospital, GΙ Unit, Athens, Greece
| | - Georgios Axiaris
- Department of Gastroenterology, Alexandra General Hospital, Athens, Greece
| | - Georgia Bellou
- Department of Gastroenterology, General Hospital Nikaias-Piraeus 'Agios Panteleimon', General Hospital Dytikis Attikis 'Agia Varvara'- Athens, Pireaus, Greece
| | - Konstantina Chalakatevaki
- 3rd Academic Department of Internal Medicine University of Athens, Sotiria General Hospital, GΙ Unit, Athens, Greece
| | - Angeliki Christidou
- Department of Gastroenterology, GHA Evaggelismos-Polykliniki, Athens, Greece
| | - Dimitrios K Christodoulou
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Ioannina, Ioannina, Greece
| | - Kalliopi Foteinogiannopoulou
- Gastroenterology Department, University Hospital of Heraklion, Medical School University of Crete, Heraklion-Crete, Greece
| | - Anthia Gatopoulou
- 2nd Department of Internal Medicine, General University Hospital of Alexandroupolis, Alexandroupolis, Greece
| | - Olga Giouleme
- 2nd Propedeutic Department of Internal Medicine, Hippocration Hospital, Aristotle University School of Medicine, Thessaloniki, Greece
| | - Konstantinos Gkoumas
- Department of Gastroenterology, Korgialenio-Mpenakeio Hellenic Red Cross Hospital, Athens, Greece
| | - Maria Κalogirou
- 2nd Propedeutic Department of Internal Medicine, Hippocration Hospital, Aristotle University School of Medicine, Thessaloniki, Greece
| | - Pantelis Karatzas
- Gastroenterology Department, Medical School of National and Kapodistrian University of Athens School of Health Sciences, General Hospital of Athens 'Laiko', Athens, Greece
| | - Konstantinos Κarmiris
- Department of Gastroenterology, Venizelion General Hospital, Heraklion-Crete, Greece
| | - Konstantinos Κatsanos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Ioannina, Ioannina, Greece
| | - Anastasia Κourikou
- Hepato-Gastroenterology/Endoscopy Unit, 2nd Department of Internal Medicine, National and Kapodistrian University of Athens, Athens General Hospital 'Heppocratio', Athens, Greece
| | - Ioannis E Κoutroubakis
- Gastroenterology Department, University Hospital of Heraklion, Medical School University of Crete, Heraklion-Crete, Greece
| | - Christos Liatsos
- Department of Gastroenterology, 401 Military Hospital of Athens, Athens, Greece
| | | | - Nicoletta Μathou
- Department of Gastroenterology, 'Konstantopoulio-Patission' General Hospital, Athens, Greece
| | - George Michalopoulos
- Department of Gastroenterology, Tzaneion General Hospital, Piraeus, Athens, Greece
| | - Aikaterini Μantaka
- Department of Gastroenterology, Chania General Hospital, Chania, Crete, Greece
| | - Penelope Nikolaou
- Department of Gastroenterology, Venizelion General Hospital, Heraklion-Crete, Greece
| | | | - George Papatheodoridis
- Gastroenterology Department, Medical School of National and Kapodistrian University of Athens School of Health Sciences, General Hospital of Athens 'Laiko', Athens, Greece
| | - Dimitrios Polymeros
- Hepatogastroenterology Unit, Second Department of Internal Medicine-Propaedeutic, Medical School- National and Kapodistrian University of Athens, Attikon University General Hospital, Athens, Greece
| | | | - Konstantinos Soufleris
- Department of Gastroenterology, Theageneio Cancer Hospital of Thessaloniki, Thessaloniki, Greece
| | - Evdoxia Stergiou
- Department of Gastroenterology, Theageneio Cancer Hospital of Thessaloniki, Thessaloniki, Greece
| | - Aggelos Theodoulou
- Department of Gastroenterology, Metaxa Memorial General Hospital, Athens, Greece
| | | | - Georgios Theoxaris
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, Patras, Greece
| | | | | | - Eftychia Tsironi
- Department of Gastroenterology, Metaxa Memorial General Hospital, Athens, Greece
| | - Maria Tzouvala
- Department of Gastroenterology, General Hospital Nikaias-Piraeus 'Agios Panteleimon', General Hospital Dytikis Attikis 'Agia Varvara'- Athens, Pireaus, Greece
| | - Nikos Viazis
- Department of Gastroenterology, GHA Evaggelismos-Polykliniki, Athens, Greece
| | | | - Giorgos Bamias
- 3rd Academic Department of Internal Medicine University of Athens, Sotiria General Hospital, GΙ Unit, Athens, Greece
| | - Evanthia Zampeli
- Department of Gastroenterology, Alexandra General Hospital, Athens, Greece
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3
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Attauabi M, Madsen GR, Bendtsen F, Burisch J, Seidelin JB. The Role of Environmental Factors Prior to Diagnosis on the Activity and Severity of Inflammatory Bowel Diseases-Results From the Prospective Population-Based Copenhagen Inflammatory Bowel Disease Inception Cohort. United European Gastroenterol J 2025. [PMID: 39878314 DOI: 10.1002/ueg2.12737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 09/30/2024] [Accepted: 10/21/2024] [Indexed: 01/31/2025] Open
Abstract
BACKGROUND The influence of environmental factors on the severity of early inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is unclear. Herein, we aimed to investigate the role of environmental factors in the initial phenotype, activity, and severity of IBD. METHODS Copenhagen IBD Inception Cohort is a prospective population-based cohort of patients with newly diagnosed IBD between May 2021 and May 2023. Data on environmental factors were captured at IBD diagnosis using International Organisation of IBD (IOIBD) and HeartDiet questionnaires. Environmental factors' influence on outcome was analyzed and odds ratios (aOR) were adjusted for age, gender, and disease characteristics (adjusted OR, aOR [95% confidence interval]). RESULTS In total, 208 and 128 patients with incident UC and CD, respectively, were included. Active smoking was associated with increased risk of CD-related hospitalization (aOR = 2.84 [1.03; 7.88]) and stricturing phenotype (aOR = 5.28 [1.76; 15.85]) but lower risk of severe UC course (aOR = 0.28 [0.08; 0.95]). Further, previous smoking was not associated with negative effects in patients with CD in terms of early need for biologics, surgery, or hospitalization. In terms of diets, daily consumption of fruits (aOR = 0.27 [0.07; 0.99]) or vegetables (aOR = 0.27 [0.09; 0.80]) was inversely associated with stricturing CD, whereas whole meal bread was associated with reduced risk of severe CD activity (aOR = 0.40 [0.16; 0.98]). CONCLUSIONS This prospective population-based study highlighted several environmental factors associated with the initial severity and activity of IBD, emphasizing their pivotal role in the initial disease burden and giving guidance to personalized patient counseling.
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Affiliation(s)
- Mohamed Attauabi
- Department of Gastroenterology and Hepatology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark
- Gastrounit, Medical Section, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents, and Adults, Hvidovre Hospital, Hvidovre, Denmark
| | - Gorm Roager Madsen
- Gastrounit, Medical Section, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents, and Adults, Hvidovre Hospital, Hvidovre, Denmark
| | - Flemming Bendtsen
- Gastrounit, Medical Section, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents, and Adults, Hvidovre Hospital, Hvidovre, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Johan Burisch
- Gastrounit, Medical Section, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents, and Adults, Hvidovre Hospital, Hvidovre, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jakob Benedict Seidelin
- Department of Gastroenterology and Hepatology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Kelly C, Sartor RB, Rawls JF. Early subclinical stages of the inflammatory bowel diseases: insights from human and animal studies. Am J Physiol Gastrointest Liver Physiol 2025; 328:G17-G31. [PMID: 39499254 PMCID: PMC11901386 DOI: 10.1152/ajpgi.00252.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 10/30/2024] [Accepted: 10/31/2024] [Indexed: 11/07/2024]
Abstract
The inflammatory bowel diseases (IBD) occur in genetically susceptible individuals that mount inappropriate immune responses to their microbiota leading to chronic intestinal inflammation. The natural history of IBD progression begins with early subclinical stages of disease that occur before clinical diagnosis. Improved understanding of those early subclinical stages could lead to new or improved strategies for IBD diagnosis, prognostication, or prevention. Here, we review our current understanding of the early subclinical stages of IBD in humans including studies from first-degree relatives of patients with IBD and members of the general population who go on to develop IBD. We also discuss representative mouse models of IBD that can be used to investigate disease dynamics and host-microbiota relationships during these early stages. In particular, we underscore how mouse models of IBD that develop disease later in life with variable penetrance may present valuable opportunities to discern early subclinical mechanisms of disease before histological inflammation and other severe symptoms become apparent.
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Affiliation(s)
- Cecelia Kelly
- Department of Molecular Genetics and Microbiology, Duke Microbiome Center, Duke University School of Medicine, Durham, North Carolina, United States
| | - R Balfour Sartor
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States
- Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, United States
| | - John F Rawls
- Department of Molecular Genetics and Microbiology, Duke Microbiome Center, Duke University School of Medicine, Durham, North Carolina, United States
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5
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Rowghani K, Patel B, Martinez-Guryn K. Dietary impact on the gut microbiome and epigenome and regulation of gut inflammation. NUTRITION IN THE CONTROL OF INFLAMMATION 2025:369-398. [DOI: 10.1016/b978-0-443-18979-1.00014-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Bronze S, Agrawal M, Colombel JF, Torres J, Ungaro RC. Review article: Prevention of inflammatory bowel disease-The path forward. Aliment Pharmacol Ther 2024; 60:1166-1175. [PMID: 39403049 PMCID: PMC12148343 DOI: 10.1111/apt.18263] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 08/13/2024] [Accepted: 08/30/2024] [Indexed: 12/13/2024]
Abstract
BACKGROUND The possibility of preventing inflammatory bowel disease (IBD) is becoming more plausible due to advances in understanding preclinical disease and successful prevention trials in other immune-mediated diseases, such as type 1 diabetes and rheumatoid arthritis. However, before that possibility becomes reality, several efforts need to occur in parallel and in a coordinated way. AIM To propose some critical steps necessary for advancing the field of IBD prediction and prevention. METHODS We reviewed the current literature to identify the necessary steps toward a preventive strategy for IBD. RESULTS The first step should determine the most robust predictive biomarkers and validate them across independent cohorts, creating a multidimensional predictive tool. The second step is to gain a better understanding of the preferences of first-degree relatives and people at risk for IBD, informing the implementation of screening and preventive strategies. Third, these efforts should contribute to the development of high-risk clinics and establish the necessary networks for disease prevention trials. CONCLUSIONS Advancing the field of IBD prediction and prevention will require a multifaceted approach, integrating biomarker discovery, understanding patient preferences, and establishing infrastructure for a collaborative network to support the practical implementation of IBD prevention strategies.
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Affiliation(s)
- Sérgio Bronze
- Gastroenterology and Hepatology Department, Unidade Local de Saúde de Santa Maria, Lisbon, Portugal
- Faculdade de Medicina de Lisboa, Universidade de Lisboa, Lisbon, Portugal
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Manasi Agrawal
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Jean-Frédéric Colombel
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Joana Torres
- Faculdade de Medicina de Lisboa, Universidade de Lisboa, Lisbon, Portugal
- Division of Gastroenterology, Hospital da luz Lisboa, Lisbon, Portugal
- Division of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
| | - Ryan C Ungaro
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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7
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Caruso R, Lo BC, Chen GY, Núñez G. Host-pathobiont interactions in Crohn's disease. Nat Rev Gastroenterol Hepatol 2024:10.1038/s41575-024-00997-y. [PMID: 39448837 DOI: 10.1038/s41575-024-00997-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/23/2024] [Indexed: 10/26/2024]
Abstract
The mammalian intestine is colonized by trillions of microorganisms that are collectively referred to as the gut microbiota. The majority of symbionts have co-evolved with their host in a mutualistic relationship that benefits both. Under certain conditions, such as in Crohn's disease, a subtype of inflammatory bowel disease, some symbionts bloom to cause disease in genetically susceptible hosts. Although the identity and function of disease-causing microorganisms or pathobionts in Crohn's disease remain largely unknown, mounting evidence from animal models suggests that pathobionts triggering Crohn's disease-like colitis inhabit certain niches and penetrate the intestinal tissue to trigger inflammation. In this Review, we discuss the distinct niches occupied by intestinal symbionts and the evidence that pathobionts triggering Crohn's disease live in the mucus layer or near the intestinal epithelium. We also discuss how Crohn's disease-associated mutations in the host disrupt intestinal homeostasis by promoting the penetration and accumulation of pathobionts in the intestinal tissue. Finally, we discuss the potential role of microbiome-based interventions in precision therapeutic strategies for the treatment of Crohn's disease.
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Affiliation(s)
- Roberta Caruso
- Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
| | - Bernard C Lo
- Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Grace Y Chen
- Department of Internal Medicine and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Gabriel Núñez
- Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
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Ma B, Hu X, Ai X, Zhang Y. Research progress of ferroptosis and inflammatory bowel disease. Biometals 2024; 37:1039-1062. [PMID: 38713412 DOI: 10.1007/s10534-024-00604-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Accepted: 04/09/2024] [Indexed: 05/08/2024]
Abstract
Inflammatory bowel disease (IBD) is a non-specific chronic inflammatory disorder of the gastrointestinal tract, imposing significant burdens on both society and individuals. As a new type of regulated cell death (RCD), ferroptosis is different from classic RCDs such as apoptosis and necrosis in cell morphology, biochemistry and genetics. The main molecular mechanisms of ferroptosis include dysregulation of iron metabolism, impaired antioxidant capacity, mitochondrial dysfunction, accumulation of lipid-associated super-oxides, and membrane disruption. In recent years, increasing evidence has shown that ferroptosis is involved in the pathophysiology of inflammatory bowel disease. However, the exact roles and underlying molecular mechanisms have not been fully elucidated. This article reviews the mechanism of ferroptosis in the occurrence and development of inflammatory bowel disease, in order to provide new ideas for the pathophysiological research of inflammatory bowel disease. Additionally, we discuss potential strategies for the prevention and treatment of inflammatory bowel disease by targeting ferroptosis.
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Affiliation(s)
- Baolian Ma
- College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, China
| | - Xiaoxue Hu
- College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, China
| | - Xiaowen Ai
- College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, China
| | - Yonglan Zhang
- College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, China.
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Chew DCH, Khoo XH, Lee TS, Chin KY, Raja Ali RA, Muhammad Nawawi KN, Wan Ibrahim NR, Hilmi I. A Systematic Review on the Increasing Incidence of Inflammatory Bowel Disease in Southeast Asia: Looking Beyond the Urbanization Phenomenon. Inflamm Bowel Dis 2024; 30:1566-1578. [PMID: 37935628 DOI: 10.1093/ibd/izad189] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Indexed: 11/09/2023]
Abstract
The incidence of inflammatory bowel disease (IBD) has been increasing in Southeast Asia (SEA) in tandem with its economic growth and urbanization over the past 2 decades. Specific characteristics of IBD in SEA are similar to East Asia and the West, such as the declining ratio of ulcerative colitis to Crohn's disease. However, exceptionally low familial aggregation is seen. Smoking is also not a common risk factor in patients with Crohn's disease. The incidence of perianal disease is higher in SEA than in Australia and is comparable to the West. In a multiracial population, such as Singapore and Malaysia, Indians have the highest incidence and prevalence rates, which are likely to be due to important putative mutations. For instance, a higher frequency of the NOD2 predisposing mutation SNP5 and IBD risk allele IGR2198a and IGR2092a were found in Indians. Although differences in the genetic constitution play an important role in the epidemiology and prognosis of IBD in SEA, the emergence of this disease offers a unique opportunity to identify potential exposomes that contribute to its pathogenesis.
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Affiliation(s)
- Deborah Chia Hsin Chew
- Gastroenterology and hepatology Unit, Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
- GUT Research Group, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Xin-Hui Khoo
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Tiong See Lee
- Department of Gastroenterology and Hepatology, Selayang Hospital, Kuala Lumpur, Malaysia
| | - Kok-Yong Chin
- Department of Pharmacology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
| | - Raja Affendi Raja Ali
- Gastroenterology and hepatology Unit, Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
- GUT Research Group, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Khairul Najmi Muhammad Nawawi
- Gastroenterology and hepatology Unit, Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
- GUT Research Group, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | | | - Ida Hilmi
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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Alexandrescu L, Nicoara AD, Tofolean DE, Herlo A, Nelson Twakor A, Tocia C, Trandafir A, Dumitru A, Dumitru E, Aftenie CF, Preotesoiu I, Dina E, Tofolean IT. Healing from Within: How Gut Microbiota Predicts IBD Treatment Success-A Systematic Review. Int J Mol Sci 2024; 25:8451. [PMID: 39126020 PMCID: PMC11313389 DOI: 10.3390/ijms25158451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2024] [Revised: 07/29/2024] [Accepted: 07/30/2024] [Indexed: 08/12/2024] Open
Abstract
Recent research indicates that the microbiome has a significant impact on the progression of inflammatory bowel disease (IBD) and that creating therapies that change its composition could positively impact the outcomes of IBD treatment. This review summarizes the results of extensive studies that examined IBD patients undergoing several therapies, including anti-TNF medication, vedolizumab, ustekinumab, probiotics, and fecal microbiota transplantation (FMT), and the alterations in their gut microbiota's composition and function. The objective was to investigate the variety and effectiveness of microbial species in order to discover new biomarkers or therapeutic targets that could improve the outcome of treatment for these patients. This research aimed to offer useful insights into personalized medicine techniques for managing IBD. Beneficial bacteria such as Faecalibacterium prausnitzii and Roseburia have been consistently linked to favorable clinical outcomes, whereas pathogenic bacteria such as Escherichia coli and Clostridioides difficile are associated with worsening disease conditions. Although many studies have examined the role of gut microbiota in IBD, there is still a need for more targeted research on the connection between specific microbial communities and treatment outcomes. This study sought to address this gap by exploring the intricate relationship between the gut microbiota composition and the effectiveness of IBD medications.
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Affiliation(s)
- Luana Alexandrescu
- Gastroenterology Department, “Sf. Apostol Andrei” Emergency County Hospital, 145 Tomis Blvd., 900591 Constanta, Romania; (L.A.); (C.T.); (A.D.); (E.D.); (E.D.); (I.T.T.)
- Medicine Faculty, “Ovidius” University of Constanta, 1 Universitatii Street, 900470 Constanta, Romania; (D.E.T.); (A.T.); (C.F.A.); (I.P.)
| | - Alina Doina Nicoara
- Medicine Faculty, “Ovidius” University of Constanta, 1 Universitatii Street, 900470 Constanta, Romania; (D.E.T.); (A.T.); (C.F.A.); (I.P.)
- Internal Medicine Department, “Sf. Apostol Andrei” Emergency County Hospital, 145 Tomis Blvd., 900591 Constanta, Romania;
| | - Doina Ecaterina Tofolean
- Medicine Faculty, “Ovidius” University of Constanta, 1 Universitatii Street, 900470 Constanta, Romania; (D.E.T.); (A.T.); (C.F.A.); (I.P.)
- Pneumology Department, “Sf. Apostol Andrei” Emergency County Hospital, 145 Tomis Blvd., 900591 Constanta, Romania
| | - Alexandra Herlo
- Department XIII, Discipline of Infectious Diseases, “Victor Babes” University of Medicine and Pharmacy Timisoara, 2 Eftimie Murgu Square, 300041 Timisoara, Romania;
| | - Andreea Nelson Twakor
- Internal Medicine Department, “Sf. Apostol Andrei” Emergency County Hospital, 145 Tomis Blvd., 900591 Constanta, Romania;
| | - Cristina Tocia
- Gastroenterology Department, “Sf. Apostol Andrei” Emergency County Hospital, 145 Tomis Blvd., 900591 Constanta, Romania; (L.A.); (C.T.); (A.D.); (E.D.); (E.D.); (I.T.T.)
- Medicine Faculty, “Ovidius” University of Constanta, 1 Universitatii Street, 900470 Constanta, Romania; (D.E.T.); (A.T.); (C.F.A.); (I.P.)
| | - Anamaria Trandafir
- Medicine Faculty, “Ovidius” University of Constanta, 1 Universitatii Street, 900470 Constanta, Romania; (D.E.T.); (A.T.); (C.F.A.); (I.P.)
| | - Andrei Dumitru
- Gastroenterology Department, “Sf. Apostol Andrei” Emergency County Hospital, 145 Tomis Blvd., 900591 Constanta, Romania; (L.A.); (C.T.); (A.D.); (E.D.); (E.D.); (I.T.T.)
| | - Eugen Dumitru
- Gastroenterology Department, “Sf. Apostol Andrei” Emergency County Hospital, 145 Tomis Blvd., 900591 Constanta, Romania; (L.A.); (C.T.); (A.D.); (E.D.); (E.D.); (I.T.T.)
- Medicine Faculty, “Ovidius” University of Constanta, 1 Universitatii Street, 900470 Constanta, Romania; (D.E.T.); (A.T.); (C.F.A.); (I.P.)
- Academy of Romanian Scientist, 3 Ilfov Street, 050044 Bucharest, Romania
| | - Cristian Florentin Aftenie
- Medicine Faculty, “Ovidius” University of Constanta, 1 Universitatii Street, 900470 Constanta, Romania; (D.E.T.); (A.T.); (C.F.A.); (I.P.)
| | - Ionela Preotesoiu
- Medicine Faculty, “Ovidius” University of Constanta, 1 Universitatii Street, 900470 Constanta, Romania; (D.E.T.); (A.T.); (C.F.A.); (I.P.)
| | - Elena Dina
- Gastroenterology Department, “Sf. Apostol Andrei” Emergency County Hospital, 145 Tomis Blvd., 900591 Constanta, Romania; (L.A.); (C.T.); (A.D.); (E.D.); (E.D.); (I.T.T.)
| | - Ioan Tiberiu Tofolean
- Gastroenterology Department, “Sf. Apostol Andrei” Emergency County Hospital, 145 Tomis Blvd., 900591 Constanta, Romania; (L.A.); (C.T.); (A.D.); (E.D.); (E.D.); (I.T.T.)
- Medicine Faculty, “Ovidius” University of Constanta, 1 Universitatii Street, 900470 Constanta, Romania; (D.E.T.); (A.T.); (C.F.A.); (I.P.)
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11
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Li Q, Wang J. The Effect of Protein Nutritional Support on Inflammatory Bowel Disease and Its Potential Mechanisms. Nutrients 2024; 16:2302. [PMID: 39064745 PMCID: PMC11280054 DOI: 10.3390/nu16142302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 07/11/2024] [Accepted: 07/13/2024] [Indexed: 07/28/2024] Open
Abstract
Inflammatory bowel disease (IBD), a complex chronic inflammatory bowel disorder that includes Crohn's disease (CD) and Ulcerative Colitis (UC), has become a globally increasing health concern. Nutrition, as an important factor influencing the occurrence and development of IBD, has attracted more and more attention. As the most important nutrient, protein can not only provide energy and nutrition required by patients, but also help repair damaged intestinal tissue, enhance immunity, and thus alleviate inflammation. Numerous studies have shown that protein nutritional support plays a significant role in the treatment and remission of IBD. This article presents a comprehensive review of the pathogenesis of IBD and analyzes and summarizes the potential mechanisms of protein nutritional support in IBD. Additionally, it provides an overview of the clinical effects of protein nutritional support in IBD and its impact on clinical complications. Research findings reveal that protein nutritional support demonstrates significant benefits in improving clinical symptoms, reducing the risk of complications, and improving quality of life in IBD patients. Therefore, protein nutritional support is expected to provide a new approach for the treatment of IBD.
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Affiliation(s)
| | - Jing Wang
- Institute of Food and Nutrition Development, Ministry of Agriculture and Rural Affairs, Beijing 100081, China;
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12
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Ciorba MA, Konnikova L, Hirota SA, Lucchetta EM, Turner JR, Slavin A, Johnson K, Condray CD, Hong S, Cressall BK, Pizarro TT, Hurtado-Lorenzo A, Heller CA, Moss AC, Swantek JL, Garrett WS. Challenges in IBD Research 2024: Preclinical Human IBD Mechanisms. Inflamm Bowel Dis 2024; 30:S5-S18. [PMID: 38778627 PMCID: PMC11491665 DOI: 10.1093/ibd/izae081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Indexed: 05/25/2024]
Abstract
Preclinical human inflammatory bowel disease (IBD) mechanisms is one of 5 focus areas of the Challenges in IBD Research 2024 document, which also includes environmental triggers, novel technologies, precision medicine, and pragmatic clinical research. Herein, we provide a comprehensive overview of current gaps in inflammatory bowel diseases research that relate to preclinical research and deliver actionable approaches to address them with a focus on how these gaps can lead to advancements in IBD interception, remission, and restoration. The document is the result of multidisciplinary input from scientists, clinicians, patients, and funders and represents a valuable resource for patient-centric research prioritization. This preclinical human IBD mechanisms section identifies major research gaps whose investigation will elucidate pathways and mechanisms that can be targeted to address unmet medical needs in IBD. Research gaps were identified in the following areas: genetics, risk alleles, and epigenetics; the microbiome; cell states and interactions; barrier function; IBD complications (specifically fibrosis and stricturing); and extraintestinal manifestations. To address these gaps, we share specific opportunities for investigation for basic and translational scientists and identify priority actions.
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Affiliation(s)
- Matthew A Ciorba
- Inflammatory Bowel Diseases Center, Division of Gastroenterology, Washington University in St. Louis, Saint Louis, MO, USA
| | - Liza Konnikova
- Departments of Pediatrics, Immunobiology, and Obstetric, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA
| | - Simon A Hirota
- Snyder Institute for Chronic Diseases, Dept. of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
| | - Elena M Lucchetta
- The Leona M. and Harry B. Helmsley Charitable Trust, New York, NY, USA
| | - Jerrold R Turner
- Departments of Pathology and Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | | | | | - Cass D Condray
- Patient Representative for the Crohn’s & Colitis Foundation, New York, NY, USA
| | - Sungmo Hong
- Patient Representative for the Crohn’s & Colitis Foundation, New York, NY, USA
| | - Brandon K Cressall
- Patient Representative for the Crohn’s & Colitis Foundation, New York, NY, USA
| | - Theresa T Pizarro
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | | | - Caren A Heller
- Research Department, Crohn’s & Colitis Foundation, New York, NY, USA
| | - Alan C Moss
- Research Department, Crohn’s & Colitis Foundation, New York, NY, USA
| | | | - Wendy S Garrett
- Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA
- The Harvard T. H. Chan Microbiome in Public Health Center, Boston, MA, USA
- Kymera Therapeutics, Watertown, MA, USA
- The Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
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13
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O'Brien CL, Summers KM, Martin NM, Carter-Cusack D, Yang Y, Barua R, Dixit OVA, Hume DA, Pavli P. The relationship between extreme inter-individual variation in macrophage gene expression and genetic susceptibility to inflammatory bowel disease. Hum Genet 2024; 143:233-261. [PMID: 38421405 PMCID: PMC11043138 DOI: 10.1007/s00439-024-02642-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 01/14/2024] [Indexed: 03/02/2024]
Abstract
The differentiation of resident intestinal macrophages from blood monocytes depends upon signals from the macrophage colony-stimulating factor receptor (CSF1R). Analysis of genome-wide association studies (GWAS) indicates that dysregulation of macrophage differentiation and response to microorganisms contributes to susceptibility to chronic inflammatory bowel disease (IBD). Here, we analyzed transcriptomic variation in monocyte-derived macrophages (MDM) from affected and unaffected sib pairs/trios from 22 IBD families and 6 healthy controls. Transcriptional network analysis of the data revealed no overall or inter-sib distinction between affected and unaffected individuals in basal gene expression or the temporal response to lipopolysaccharide (LPS). However, the basal or LPS-inducible expression of individual genes varied independently by as much as 100-fold between subjects. Extreme independent variation in the expression of pairs of HLA-associated transcripts (HLA-B/C, HLA-A/F and HLA-DRB1/DRB5) in macrophages was associated with HLA genotype. Correlation analysis indicated the downstream impacts of variation in the immediate early response to LPS. For example, variation in early expression of IL1B was significantly associated with local SNV genotype and with subsequent peak expression of target genes including IL23A, CXCL1, CXCL3, CXCL8 and NLRP3. Similarly, variation in early IFNB1 expression was correlated with subsequent expression of IFN target genes. Our results support the view that gene-specific dysregulation in macrophage adaptation to the intestinal milieu is associated with genetic susceptibility to IBD.
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Affiliation(s)
- Claire L O'Brien
- Centre for Research in Therapeutics Solutions, Faculty of Science and Technology, University of Canberra, Canberra, ACT, Australia
- Inflammatory Bowel Disease Research Group, Canberra Hospital, Canberra, ACT, Australia
| | - Kim M Summers
- Mater Research Institute-University of Queensland, Translational Research Institute, Brisbane, QLD, Australia
| | - Natalia M Martin
- Inflammatory Bowel Disease Research Group, Canberra Hospital, Canberra, ACT, Australia
| | - Dylan Carter-Cusack
- Mater Research Institute-University of Queensland, Translational Research Institute, Brisbane, QLD, Australia
| | - Yuanhao Yang
- Mater Research Institute-University of Queensland, Translational Research Institute, Brisbane, QLD, Australia
| | - Rasel Barua
- Inflammatory Bowel Disease Research Group, Canberra Hospital, Canberra, ACT, Australia
| | - Ojas V A Dixit
- Centre for Research in Therapeutics Solutions, Faculty of Science and Technology, University of Canberra, Canberra, ACT, Australia
| | - David A Hume
- Mater Research Institute-University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
| | - Paul Pavli
- Inflammatory Bowel Disease Research Group, Canberra Hospital, Canberra, ACT, Australia.
- School of Medicine and Psychology, College of Health and Medicine, Australian National University, Canberra, ACT, Australia.
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14
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The Critical Assessment of Genome Interpretation Consortium, Jain S, Bakolitsa C, Brenner SE, Radivojac P, Moult J, Repo S, Hoskins RA, Andreoletti G, Barsky D, Chellapan A, Chu H, Dabbiru N, Kollipara NK, Ly M, Neumann AJ, Pal LR, Odell E, Pandey G, Peters-Petrulewicz RC, Srinivasan R, Yee SF, Yeleswarapu SJ, Zuhl M, Adebali O, Patra A, Beer MA, Hosur R, Peng J, Bernard BM, Berry M, Dong S, Boyle AP, Adhikari A, Chen J, Hu Z, Wang R, Wang Y, Miller M, Wang Y, Bromberg Y, Turina P, Capriotti E, Han JJ, Ozturk K, Carter H, Babbi G, Bovo S, Di Lena P, Martelli PL, Savojardo C, Casadio R, Cline MS, De Baets G, Bonache S, Díez O, Gutiérrez-Enríquez S, Fernández A, Montalban G, Ootes L, Özkan S, Padilla N, Riera C, De la Cruz X, Diekhans M, Huwe PJ, Wei Q, Xu Q, Dunbrack RL, Gotea V, Elnitski L, Margolin G, Fariselli P, Kulakovskiy IV, Makeev VJ, Penzar DD, Vorontsov IE, Favorov AV, Forman JR, Hasenahuer M, Fornasari MS, Parisi G, Avsec Z, Çelik MH, Nguyen TYD, Gagneur J, Shi FY, Edwards MD, Guo Y, Tian K, Zeng H, Gifford DK, Göke J, Zaucha J, Gough J, Ritchie GRS, Frankish A, Mudge JM, Harrow J, Young EL, et alThe Critical Assessment of Genome Interpretation Consortium, Jain S, Bakolitsa C, Brenner SE, Radivojac P, Moult J, Repo S, Hoskins RA, Andreoletti G, Barsky D, Chellapan A, Chu H, Dabbiru N, Kollipara NK, Ly M, Neumann AJ, Pal LR, Odell E, Pandey G, Peters-Petrulewicz RC, Srinivasan R, Yee SF, Yeleswarapu SJ, Zuhl M, Adebali O, Patra A, Beer MA, Hosur R, Peng J, Bernard BM, Berry M, Dong S, Boyle AP, Adhikari A, Chen J, Hu Z, Wang R, Wang Y, Miller M, Wang Y, Bromberg Y, Turina P, Capriotti E, Han JJ, Ozturk K, Carter H, Babbi G, Bovo S, Di Lena P, Martelli PL, Savojardo C, Casadio R, Cline MS, De Baets G, Bonache S, Díez O, Gutiérrez-Enríquez S, Fernández A, Montalban G, Ootes L, Özkan S, Padilla N, Riera C, De la Cruz X, Diekhans M, Huwe PJ, Wei Q, Xu Q, Dunbrack RL, Gotea V, Elnitski L, Margolin G, Fariselli P, Kulakovskiy IV, Makeev VJ, Penzar DD, Vorontsov IE, Favorov AV, Forman JR, Hasenahuer M, Fornasari MS, Parisi G, Avsec Z, Çelik MH, Nguyen TYD, Gagneur J, Shi FY, Edwards MD, Guo Y, Tian K, Zeng H, Gifford DK, Göke J, Zaucha J, Gough J, Ritchie GRS, Frankish A, Mudge JM, Harrow J, Young EL, Yu Y, Huff CD, Murakami K, Nagai Y, Imanishi T, Mungall CJ, Jacobsen JOB, Kim D, Jeong CS, Jones DT, Li MJ, Guthrie VB, Bhattacharya R, Chen YC, Douville C, Fan J, Kim D, Masica D, Niknafs N, Sengupta S, Tokheim C, Turner TN, Yeo HTG, Karchin R, Shin S, Welch R, Keles S, Li Y, Kellis M, Corbi-Verge C, Strokach AV, Kim PM, Klein TE, Mohan R, Sinnott-Armstrong NA, Wainberg M, Kundaje A, Gonzaludo N, Mak ACY, Chhibber A, Lam HYK, Dahary D, Fishilevich S, Lancet D, Lee I, Bachman B, Katsonis P, Lua RC, Wilson SJ, Lichtarge O, Bhat RR, Sundaram L, Viswanath V, Bellazzi R, Nicora G, Rizzo E, Limongelli I, Mezlini AM, Chang R, Kim S, Lai C, O’Connor R, Topper S, van den Akker J, Zhou AY, Zimmer AD, Mishne G, Bergquist TR, Breese MR, Guerrero RF, Jiang Y, Kiga N, Li B, Mort M, Pagel KA, Pejaver V, Stamboulian MH, Thusberg J, Mooney SD, Teerakulkittipong N, Cao C, Kundu K, Yin Y, Yu CH, Kleyman M, Lin CF, Stackpole M, Mount SM, Eraslan G, Mueller NS, Naito T, Rao AR, Azaria JR, Brodie A, Ofran Y, Garg A, Pal D, Hawkins-Hooker A, Kenlay H, Reid J, Mucaki EJ, Rogan PK, Schwarz JM, Searls DB, Lee GR, Seok C, Krämer A, Shah S, Huang CV, Kirsch JF, Shatsky M, Cao Y, Chen H, Karimi M, Moronfoye O, Sun Y, Shen Y, Shigeta R, Ford CT, Nodzak C, Uppal A, Shi X, Joseph T, Kotte S, Rana S, Rao A, Saipradeep VG, Sivadasan N, Sunderam U, Stanke M, Su A, Adzhubey I, Jordan DM, Sunyaev S, Rousseau F, Schymkowitz J, Van Durme J, Tavtigian SV, Carraro M, Giollo M, Tosatto SCE, Adato O, Carmel L, Cohen NE, Fenesh T, Holtzer T, Juven-Gershon T, Unger R, Niroula A, Olatubosun A, Väliaho J, Yang Y, Vihinen M, Wahl ME, Chang B, Chong KC, Hu I, Sun R, Wu WKK, Xia X, Zee BC, Wang MH, Wang M, Wu C, Lu Y, Chen K, Yang Y, Yates CM, Kreimer A, Yan Z, Yosef N, Zhao H, Wei Z, Yao Z, Zhou F, Folkman L, Zhou Y, Daneshjou R, Altman RB, Inoue F, Ahituv N, Arkin AP, Lovisa F, Bonvini P, Bowdin S, Gianni S, Mantuano E, Minicozzi V, Novak L, Pasquo A, Pastore A, Petrosino M, Puglisi R, Toto A, Veneziano L, Chiaraluce R, Ball MP, Bobe JR, Church GM, Consalvi V, Cooper DN, Buckley BA, Sheridan MB, Cutting GR, Scaini MC, Cygan KJ, Fredericks AM, Glidden DT, Neil C, Rhine CL, Fairbrother WG, Alontaga AY, Fenton AW, Matreyek KA, Starita LM, Fowler DM, Löscher BS, Franke A, Adamson SI, Graveley BR, Gray JW, Malloy MJ, Kane JP, Kousi M, Katsanis N, Schubach M, Kircher M, Mak ACY, Tang PLF, Kwok PY, Lathrop RH, Clark WT, Yu GK, LeBowitz JH, Benedicenti F, Bettella E, Bigoni S, Cesca F, Mammi I, Marino-Buslje C, Milani D, Peron A, Polli R, Sartori S, Stanzial F, Toldo I, Turolla L, Aspromonte MC, Bellini M, Leonardi E, Liu X, Marshall C, McCombie WR, Elefanti L, Menin C, Meyn MS, Murgia A, Nadeau KCY, Neuhausen SL, Nussbaum RL, Pirooznia M, Potash JB, Dimster-Denk DF, Rine JD, Sanford JR, Snyder M, Cote AG, Sun S, Verby MW, Weile J, Roth FP, Tewhey R, Sabeti PC, Campagna J, Refaat MM, Wojciak J, Grubb S, Schmitt N, Shendure J, Spurdle AB, Stavropoulos DJ, Walton NA, Zandi PP, Ziv E, Burke W, Chen F, Carr LR, Martinez S, Paik J, Harris-Wai J, Yarborough M, Fullerton SM, Koenig BA, McInnes G, Shigaki D, Chandonia JM, Furutsuki M, Kasak L, Yu C, Chen R, Friedberg I, Getz GA, Cong Q, Kinch LN, Zhang J, Grishin NV, Voskanian A, Kann MG, Tran E, Ioannidis NM, Hunter JM, Udani R, Cai B, Morgan AA, Sokolov A, Stuart JM, Minervini G, Monzon AM, Batzoglou S, Butte AJ, Greenblatt MS, Hart RK, Hernandez R, Hubbard TJP, Kahn S, O’Donnell-Luria A, Ng PC, Shon J, Veltman J, Zook JM. CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods. Genome Biol 2024; 25:53. [PMID: 38389099 PMCID: PMC10882881 DOI: 10.1186/s13059-023-03113-6] [Show More Authors] [Citation(s) in RCA: 27] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 11/17/2023] [Indexed: 02/24/2024] Open
Abstract
BACKGROUND The Critical Assessment of Genome Interpretation (CAGI) aims to advance the state-of-the-art for computational prediction of genetic variant impact, particularly where relevant to disease. The five complete editions of the CAGI community experiment comprised 50 challenges, in which participants made blind predictions of phenotypes from genetic data, and these were evaluated by independent assessors. RESULTS Performance was particularly strong for clinical pathogenic variants, including some difficult-to-diagnose cases, and extends to interpretation of cancer-related variants. Missense variant interpretation methods were able to estimate biochemical effects with increasing accuracy. Assessment of methods for regulatory variants and complex trait disease risk was less definitive and indicates performance potentially suitable for auxiliary use in the clinic. CONCLUSIONS Results show that while current methods are imperfect, they have major utility for research and clinical applications. Emerging methods and increasingly large, robust datasets for training and assessment promise further progress ahead.
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15
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Rudbaek JJ, Agrawal M, Torres J, Mehandru S, Colombel JF, Jess T. Deciphering the different phases of preclinical inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2024; 21:86-100. [PMID: 37950021 PMCID: PMC11148654 DOI: 10.1038/s41575-023-00854-4] [Citation(s) in RCA: 52] [Impact Index Per Article: 52.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/03/2023] [Indexed: 11/12/2023]
Abstract
Inflammatory bowel disease (IBD) is an immune-mediated inflammatory disease (IMID) of the gastrointestinal tract and includes two subtypes: Crohn's disease and ulcerative colitis. It is well-recognized that IBD is associated with a complex multifactorial aetiology that includes genetic predisposition and environmental exposures, with downstream dysregulation of systemic immune function and host-microbial interactions in the local environment in the gut. Evidence to support the notion of a multistage development of IBD is growing, as has been observed in other IMIDs such as rheumatoid arthritis and systemic lupus erythematosus. With the rising worldwide incidence of IBD, it is increasingly important to understand the complex interplay of pathological events during the different stages of disease development to enable IBD prediction and prevention strategies. In this article, we review comprehensively the current evidence pertaining to the preclinical phase of IBD, including at-risk, initiation and expansion phases. We also discuss the framework of preclinical IBD, expanding on underlying pathways in IBD development, future research directions and IBD development in the context of other IMIDs.
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Affiliation(s)
- Jonas J Rudbaek
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
- Section for Biomarkers, Immunology and Antibodies, Department for Congenital Disorders, Statens Serum Institut, Copenhangen, Denmark
| | - Manasi Agrawal
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Joana Torres
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
- Division of Gastroenterology, Hospital da Luz, Lisbon, Portugal
- Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Saurabh Mehandru
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jean-Frederic Colombel
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Tine Jess
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark.
- Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark.
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16
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Gürsoy UK, Gürsoy M, Loimaranta V, Rautava J. Salivary Th17 cytokine, human β-defensin 1-3, and salivary scavenger and agglutinin levels in Crohn's disease. Clin Oral Investig 2024; 28:108. [PMID: 38246944 PMCID: PMC10800300 DOI: 10.1007/s00784-024-05509-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 01/11/2024] [Indexed: 01/23/2024]
Abstract
OBJECTIVES Crohn's disease patients, who are prone to develop periodontal diseases, may carry genetic defects in their Th17 cytokine, human beta-defensin (hBD) 1-3, and salivary and scavenger agglutinin (SALSA) expressions. Biochemical composition of saliva reflects the oral consequences of systemic immune response modifications. Our aim was to evaluate the salivary Th17 cytokine, epithelial hBD 1-3, and SALSA levels in relation to Crohn's disease. MATERIALS AND METHODS This cross-sectional study included 42 Crohn's disease patients and 34 systemically healthy controls. Periodontal and dental indexes were measured, and stimulated saliva samples were collected. Salivary Th17 cytokine levels were analyzed by multiplex technique, and hBD 1-3 and SALSA levels by enzyme-linked immunosorbent assay. RESULTS There were 19 gingivitis and 11 initial periodontitis patients in the Crohn's disease group, and 15 gingivitis and 4 initial periodontitis in the control group. In comparison to controls, higher salivary Th17 cytokine levels were observed in Crohn's disease patients. No statistical difference was observed between Crohn's disease and control groups in terms of their salivary hBD 1-3 and SALSA levels. Based on the regression analysis, there is no independent association between Crohn's disease and salivary Th17 cytokine levels. CONCLUSIONS Crohn's disease does not relate to salivary antimicrobial hBD 1-3 or SALSA levels. While Crohn's disease patients have higher salivary Th17 cytokine levels in comparison to systemically healthy controls, an independent association between Crohn's disease and Th17 cytokine profile is still missing. CLINICAL RELEVANCE Diminished Th17 cytokine response in Crohn's disease, which might be related to genetic susceptibility, can be also visualized in saliva.
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Affiliation(s)
- Ulvi Kahraman Gürsoy
- Department of Periodontology, Institute of Dentistry, University of Turku, 20014, Turku, Finland.
| | - Mervi Gürsoy
- Department of Periodontology, Institute of Dentistry, University of Turku, 20014, Turku, Finland
- Welfare Division, Oral Health Care, 20540, Turku, Finland
| | - Vuokko Loimaranta
- Department of Periodontology, Institute of Dentistry, University of Turku, 20014, Turku, Finland
| | - Jaana Rautava
- Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, 00014, Helsinki, Finland
- HUS Diagnostic Center, HUSLAB, Helsinki University Hospital, 00260, Helsinki, Finland
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17
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El Hadad J, Schreiner P, Vavricka SR, Greuter T. The Genetics of Inflammatory Bowel Disease. Mol Diagn Ther 2024; 28:27-35. [PMID: 37847439 PMCID: PMC10787003 DOI: 10.1007/s40291-023-00678-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/26/2023] [Indexed: 10/18/2023]
Abstract
The genetic background of inflammatory bowel disease, both Crohn's disease and ulcerative colitis, has been known for more than 2 decades. In the last 20 years, genome-wide association studies have dramatically increased our knowledge on the genetics of inflammatory bowel disease with more than 200 risk genes having been identified. Paralleling this increasing knowledge, the armamentarium of inflammatory bowel disease medications has been growing constantly. With more available therapeutic options, treatment decisions become more complex, with still many patients experiencing a debilitating disease course and a loss of response to treatment over time. With a better understanding of the disease, more effective personalized treatment strategies are looming on the horizon. Genotyping has long been considered a strategy for treatment decisions, such as the detection of thiopurine S-methyltransferase and nudix hydrolase 15 polymorphisms before the initiation of azathioprine. However, although many risk genes have been identified in inflammatory bowel disease, a substantial impact of genetic risk assessment on therapeutic strategies and disease outcome is still missing. In this review, we discuss the genetic background of inflammatory bowel disease, with a particular focus on the latest advances in the field and their potential impact on management decisions.
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Affiliation(s)
- Jasmina El Hadad
- Department of Internal Medicine, Triemli Hospital, Zurich, Switzerland
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Philipp Schreiner
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Stephan R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
- Center for Gastroenterology and Hepatology, Zurich, Switzerland
| | - Thomas Greuter
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
- Division of Gastroenterology and Hepatology, University Hospital Lausanne-CHUV, Lausanne, Switzerland.
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, GZO Zurich Regional Health Center, Spitalstrasse 66, 8620, Wetzikon, Switzerland.
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18
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Ahadi M, Rouhbakhsh Zahmatkesh MR, Ebrahimi P, AkbariRad M. The Role of Dietary Habits in the Pathogenesis and Development of Inflammatory Bowel Disease: A Narrative Review. Middle East J Dig Dis 2024; 16:5-11. [PMID: 39050099 PMCID: PMC11264837 DOI: 10.34172/mejdd.2024.362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 11/25/2023] [Indexed: 07/27/2024] Open
Abstract
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic immune-mediated disease. The incidence of IBD is influenced by various genetic and environmental factors, with dietary habits gaining significant scientific interest. While the role of diet in the pathogenesis and development of IBD is still debated, recent studies have demonstrated its potential impact. However, conflicting findings exist regarding the efficacy of dietary interventions in the treatment and control of IBD. This review aimed to summarize the current understanding of the relationship between diet and IBD, highlighting the different perspectives and reasonings observed in recent studies. Overall, it has been shown that dietary habits play a role in the incidence of IBD, and adopting a controlled dietary approach may help manage the disease. Consequently, diet can be considered a predictive and prognostic factor in IBD.
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Affiliation(s)
- Mitra Ahadi
- Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran
| | | | - Parisa Ebrahimi
- Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran
| | - Mina AkbariRad
- Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran
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19
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Salvatori S, Neri B, Marafini I, Brigida M, Monteleone G. Emerging oral drug options for ulcerative colitis. Expert Opin Emerg Drugs 2023; 28:191-201. [PMID: 37668153 DOI: 10.1080/14728214.2023.2254686] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 08/22/2023] [Accepted: 08/30/2023] [Indexed: 09/06/2023]
Abstract
INTRODUCTION Despite the availability of a variety of therapeutic compounds and improved management strategies, one-third of UC patients with moderate-to-severe disease do not benefit from the existing treatments or experience drug-related side effects. This has boosted intensive research focusing on the development of new drugs for UC therapy. This article aims to summarize the available evidence on oral drugs, which are now being explored in clinical trials or are ready to enter the clinics. AREAS COVERED From May 15 to June 11, we searched on PubMed using the keywords 'oral drugs ulcerative colitis,' 'ulcerative colitis clinical trials,' 'UC phase 2 and 3 trials' excluding case reports, case series, phase 1 and 4 studies, and studies about approved therapies. EXPERT OPINION The findings discussed in this article suggest that the future treatment of UC patients will be probably characterized by the possibility of using various small-molecule drugs. All these new compounds, even those belonging to the same class, differ in terms of efficacy and safety. Identification of predictors of response could help optimize the efficacy and safety of these treatments, thus improving resource allocation through a pretreatment stratification of patients.
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Affiliation(s)
- Silvia Salvatori
- Gastroenterology Unit, Policlinico Universitario Tor Vergata, Rome, Italy
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Benedetto Neri
- Gastroenterology Unit, Policlinico Universitario Tor Vergata, Rome, Italy
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Irene Marafini
- Gastroenterology Unit, Policlinico Universitario Tor Vergata, Rome, Italy
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Mattia Brigida
- Gastroenterology Unit, Policlinico Universitario Tor Vergata, Rome, Italy
| | - Giovanni Monteleone
- Gastroenterology Unit, Policlinico Universitario Tor Vergata, Rome, Italy
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
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20
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Martini GR, Tikhonova E, Rosati E, DeCelie MB, Sievers LK, Tran F, Lessing M, Bergfeld A, Hinz S, Nikolaus S, Kümpers J, Matysiak A, Hofmann P, Saggau C, Schneiders S, Kamps AK, Jacobs G, Lieb W, Maul J, Siegmund B, Seegers B, Hinrichsen H, Oberg HH, Wesch D, Bereswill S, Heimesaat MM, Rupp J, Kniemeyer O, Brakhage AA, Brunke S, Hube B, Aden K, Franke A, Iliev ID, Scheffold A, Schreiber S, Bacher P. Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic T H1 cell responses in Crohn's disease. Nat Med 2023; 29:2602-2614. [PMID: 37749331 PMCID: PMC10579100 DOI: 10.1038/s41591-023-02556-5] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 08/22/2023] [Indexed: 09/27/2023]
Abstract
Aberrant CD4+ T cell reactivity against intestinal microorganisms is considered to drive mucosal inflammation in inflammatory bowel diseases. The disease-relevant microbial species and the corresponding microorganism-specific, pathogenic T cell phenotypes remain largely unknown. In the present study, we identified common gut commensal and food-derived yeasts, as direct activators of altered CD4+ T cell reactions in patients with Crohn's disease (CD). Yeast-responsive CD4+ T cells in CD display a cytotoxic T helper cell (TH1 cell) phenotype and show selective expansion of T cell clones that are highly cross-reactive to several commensal, as well as food-derived, fungal species. This indicates cross-reactive T cell selection by repeated encounter with conserved fungal antigens in the context of chronic intestinal disease. Our results highlighted a role of yeasts as drivers of aberrant CD4+ T cell reactivity in patients with CD and suggest that both gut-resident fungal commensals and daily dietary intake of yeasts might contribute to chronic activation of inflammatory CD4+ T cell responses in patients with CD.
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Affiliation(s)
- Gabriela Rios Martini
- Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Ekaterina Tikhonova
- Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Elisa Rosati
- Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Meghan Bialt DeCelie
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA
- Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA
- Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Laura Katharina Sievers
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
- Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Florian Tran
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
- Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Matthias Lessing
- Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Arne Bergfeld
- Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Sophia Hinz
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
- Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Susanna Nikolaus
- Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Julia Kümpers
- Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Anna Matysiak
- Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Philipp Hofmann
- Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Carina Saggau
- Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Stephan Schneiders
- Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Ann-Kristin Kamps
- Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Gunnar Jacobs
- Institute of Epidemiology, Christian-Albrechts-University of Kiel and popgen Biobank, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Wolfgang Lieb
- Institute of Epidemiology, Christian-Albrechts-University of Kiel and popgen Biobank, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Jochen Maul
- Gastroenterologie am Bayerischen Platz, Berlin, Germany
- Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - Britta Siegmund
- Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | | | | | - Hans-Heinrich Oberg
- Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Daniela Wesch
- Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Stefan Bereswill
- Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - Markus M Heimesaat
- Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - Jan Rupp
- Department of Infectious Diseases and Microbiology, University of Lübeck, Lübeck, Germany
| | - Olaf Kniemeyer
- Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute, Jena, Germany
| | - Axel A Brakhage
- Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute, Jena, Germany
- Friedrich Schiller Universität, Jena, Germany
| | - Sascha Brunke
- Institute of Microbiology, Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute, Jena, Germany
| | - Bernhard Hube
- Friedrich Schiller Universität, Jena, Germany
- Institute of Microbiology, Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute, Jena, Germany
| | - Konrad Aden
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
- Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Andre Franke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Iliyan D Iliev
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA
- Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA
- Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Alexander Scheffold
- Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Stefan Schreiber
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
- Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Petra Bacher
- Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.
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21
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Axenfeld E, Katz S, Faye AS. Management Considerations for the Older Adult With Inflammatory Bowel Disease. Gastroenterol Hepatol (N Y) 2023; 19:592-599. [PMID: 38404957 PMCID: PMC10882858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/27/2024]
Abstract
As the prevalence of older adults with inflammatory bowel disease (IBD) is rising, understanding the unique challenges in both diagnosis and management is becoming increasingly important. Knowledge of phenotypic differences as well as overlapping symptoms with other medical conditions is critical to obtaining a timely diagnosis of IBD in older adults. Although older adults with IBD are at higher risk for adverse events compared with younger adults with IBD, recent data have suggested that ongoing disease activity may be a significant driver of adverse clinical outcomes rather than use of current treatment modalities. Ultimately, earlier and effective treatments can improve outcomes and quality of life for older adults with IBD. However, to help improve medical decision-making, clinicians must move away from the use of chronological age alone and begin to integrate measures of biological age, such as frailty and sarcopenia, into risk stratification tools. This article reviews the management considerations for older adults with IBD and provides the rationale for incorporating measures of biological age into current practice.
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Affiliation(s)
- Ellen Axenfeld
- Division of Gastroenterology and Hepatology, Department of Medicine, New York University Langone Health, New York, New York
| | - Seymour Katz
- Division of Gastroenterology and Hepatology, Department of Medicine, New York University Langone Health, New York, New York
- Inflammatory Bowel Disease Center, Division of Gastroenterology and Hepatology, New York University Langone Health, New York, New York
| | - Adam S. Faye
- Division of Gastroenterology and Hepatology, Department of Medicine, New York University Langone Health, New York, New York
- Inflammatory Bowel Disease Center, Division of Gastroenterology and Hepatology, New York University Langone Health, New York, New York
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22
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Fang YX, Liu YQ, Hu YM, Yang YY, Zhang DJ, Jiang CH, Wang JH, Zhang J. Shaoyao decoction restores the mucus layer in mice with DSS-induced colitis by regulating Notch signaling pathway. JOURNAL OF ETHNOPHARMACOLOGY 2023; 308:116258. [PMID: 36806347 DOI: 10.1016/j.jep.2023.116258] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 02/05/2023] [Accepted: 02/07/2023] [Indexed: 06/16/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Restoring the mucus layer is a potential strategy for treating ulcerative colitis (UC). Previous studies reported that a Chinese medicine formula Shaoyao Decoction (SYD) effectively improved UC. However, the role and mechanism of SYD in restoring the mucus layer are still vague. AIM OF THE STUDY This study aimed to research the therapeutical effects and unravel the involved mechanism of SYD on DSS-evoked UC. MATERIALS AND METHODS First, the constituents of SYD were detected by UPLC-QTOF-MS/MS. Then, the DSS-induced UC model was introduced to investigate the pharmacologic action and molecular mechanism of SYD on UC. Pharmacodynamic indicators were assessed including body weight, colon length, ulcerations, disease activity index (DAI), inflammatory cytokines and histological parameters. To investigate the integrality and functions of the mucous layer, AB-PAS stain and UEA-1 stain were used to evaluate the completeness of mucous layer, as well as the maturation of goblet cells (GCs). The bacterial invasion was detected by fluorescence in situ hybridization. As to mechanism exploration, the expressions of Notch/Hes1 pathway were investigated by using agonists in lipopolysaccharides (LPS) -stimulated LS174T cell. RESULTS After modeling in mice, SYD remarkedly ameliorated the symptoms of mouse colitis, the expression of pro-inflammatory factors declined, and increased IL-10 expression was observed in SYD-treated mice. Besides, SYD repaired the structure of the mucus layer and prevented bacterial invasion. Mechanism investigation discovered that SYD promoted GCs differentiation by inhibiting the Notch pathway, which was consistent with the results in LPS-challenged LS174 cell. CONCLUSIONS These findings demonstrated that SYD could restore the mucus layer to prevent UC via suppressing the Notch signaling pathway, which provided evidences for the UC treatment of SYD in the clinic.
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Affiliation(s)
- Yu-Xi Fang
- Department of Gastroenterology, Nanjing Lishui District Hospital of Traditional Chinese Medicine, Nanjing, 211200, PR China; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, PR China
| | - You-Qian Liu
- Department of Gastroenterology, Nanjing Lishui District Hospital of Traditional Chinese Medicine, Nanjing, 211200, PR China
| | - Yi-Min Hu
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, PR China
| | - Yuan-Yuan Yang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, PR China
| | - Dong-Jian Zhang
- Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, PR China
| | - Cui-Hua Jiang
- Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, PR China
| | - Jian-Hua Wang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, PR China.
| | - Jian Zhang
- Department of Gastroenterology, Nanjing Lishui District Hospital of Traditional Chinese Medicine, Nanjing, 211200, PR China; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, PR China.
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23
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Holman J, Hurd M, Moses PL, Mawe GM, Zhang T, Ishaq SL, Li Y. Interplay of broccoli/broccoli sprout bioactives with gut microbiota in reducing inflammation in inflammatory bowel diseases. J Nutr Biochem 2023; 113:109238. [PMID: 36442719 PMCID: PMC9974906 DOI: 10.1016/j.jnutbio.2022.109238] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 09/21/2022] [Accepted: 11/23/2022] [Indexed: 11/27/2022]
Abstract
Inflammatory Bowel Diseases (IBD) are chronic, reoccurring, and debilitating conditions characterized by inflammation in the gastrointestinal tract, some of which can lead to more systemic complications and can include autoimmune dysfunction, a change in the taxonomic and functional structure of microbial communities in the gut, and complicated burdens in a person's daily life. Like many diseases based in chronic inflammation, research on IBD has pointed towards a multifactorial origin involving factors of the person's lifestyle, immune system, associated microbial communities, and environmental conditions. Treatment currently exists only as palliative care, and seeks to disrupt the feedback loop of symptoms by reducing inflammation and allowing as much of a return to homeostasis as possible. Various anti-inflammatory options have been explored, and this review focuses on the use of diet as an alternative means of improving gut health. Specifically, we highlight the connection between the role of sulforaphane from cruciferous vegetables in regulating inflammation and in modifying microbial communities, and to break down the role they play in IBD.
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Affiliation(s)
- Johanna Holman
- School of Food and Agriculture, University of Maine, Orono, Maine, USA
| | - Molly Hurd
- Larner College of Medicine, University of Vermont, Burlington, Vermont, USA
| | - Peter L Moses
- Larner College of Medicine, University of Vermont, Burlington, Vermont, USA; Finch Therapeutics, Somerville, Massachusetts, USA
| | - Gary M Mawe
- Larner College of Medicine, University of Vermont, Burlington, Vermont, USA
| | - Tao Zhang
- School of Pharmacy and Pharmaceutical Sciences, SUNY Binghamton University, Johnson City, New York, USA
| | - Suzanne L Ishaq
- School of Food and Agriculture, University of Maine, Orono, Maine, USA.
| | - Yanyan Li
- School of Food and Agriculture, University of Maine, Orono, Maine, USA.
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24
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Ali FE, Ibrahim IM, Ghogar OM, Abd-alhameed EK, Althagafy HS, Hassanein EH. Therapeutic interventions target the NLRP3 inflammasome in ulcerative colitis: Comprehensive study. World J Gastroenterol 2023; 29:1026-1053. [PMID: 36844140 PMCID: PMC9950862 DOI: 10.3748/wjg.v29.i6.1026] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 12/29/2023] [Accepted: 01/29/2023] [Indexed: 02/10/2023] Open
Abstract
One of the significant health issues in the world is the prevalence of ulcerative colitis (UC). UC is a chronic disorder that mainly affects the colon, beginning with the rectum, and can progress from asymptomatic mild inflammation to extensive inflammation of the entire colon. Understanding the underlying molecular mechanisms of UC pathogenesis emphasizes the need for innovative therapeutic approaches based on identifying molecular targets. Interestingly, in response to cellular injury, the NLR family pyrin domain containing 3 (NLRP3) inflammasome is a crucial part of the inflammation and immunological reaction by promoting caspase-1 activation and the release of interleukin-1β. This review discusses the mechanisms of NLRP3 inflammasome activation by various signals and its regulation and impact on UC.
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Affiliation(s)
- Fares E.M Ali
- Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
| | - Islam M. Ibrahim
- Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
| | - Osama M Ghogar
- Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
| | - Esraa K. Abd-alhameed
- Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 12345, Egypt
| | - Hanan S. Althagafy
- Department of Biochemistry, Faculty of Science, University of Jeddah, Jeddah 12345, Saudi Arabia
| | - Emad H.M. Hassanein
- Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
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25
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Truta B, Begum F, Datta LW, NIDDK IBD Genetics Consortium, Brant SR. Inflammatory Bowel Diseases Before and After 1990. GASTRO HEP ADVANCES 2023; 2:22-32. [PMID: 36686985 PMCID: PMC9851382 DOI: 10.1016/j.gastha.2022.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND AND AIMS Inflammatory bowel disease (IBD) is caused by interaction of genetic and environmental risk factors. We evaluated potential determinants of the post-1990 increased incidence in North America. METHODS Using fitted generalized linear models, we assessed clinical features, smoking and genetic risk scores (GRS) for Crohn's disease (CD) and ulcerative colitis (UC) in the National Institutes of Diabetes, Digestion and Kidney Diseases IBD Genetics Consortium database, before and post 1990. RESULTS Among 2744 patients (55% CD, 42.2% UC), smoking status and GRS were the main determinants of diagnosis age. After 1990, smoking at diagnosis declined significantly in both UC and CD (34.1% vs 20.8%, P < .001, and 14.7% vs 8.7%, P = .06, respectively). In UC, ex-smoking increased (9% vs 15%, P < .001), and nonsmoking rates remained unchanged, whereas in CD, ex-smoking remained unchanged. CD-GRS and IBD-GRS were significantly associated with young diagnosis age, Jewish ethnicity, IBD family history, and surgery. CD-GRS showed a borderline significant decrease (P = .058) in multivariate analysis post 1990 but only when excluding surgery in the model; surgery significantly decreased post 1990 in both CD and UC. CD-GRS inversely correlated with smoking at diagnosis (P < .001) suggesting that, in the presence of smoking, CD may only require a low genetic risk to develop. CONCLUSION Significantly increase in ex-smoking correlates with UC incidence post 1990. Conversely, smoking risk decreased significantly post 1990 despite rising CD incidence. CD-GRS likewise trended to decrease post 1990 only when not accounting for a significant decrease in CD surgery. We therefore deduce that unaccounted risk factors (eg, dietary, obesity, antibiotic use, improved hygiene, etc.) or greater detection or presence of mild CD may underlie post-1990 increased CD incidence.
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Affiliation(s)
- Brindusa Truta
- Division of Gastroenterology, Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ferdouse Begum
- Division of Gastroenterology, Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Johns Hopkins University School of Medicine, Baltimore, Maryland;,Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
| | - Lisa Wu Datta
- Division of Gastroenterology, Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | - Steven R. Brant
- Division of Gastroenterology, Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Johns Hopkins University School of Medicine, Baltimore, Maryland;,Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland;,Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers Robert Wood Johnson Medical School, the Rutgers Crohns and Colitis Center of New Jersey, New Brunswick, New Jersey,Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers University, New Brunswick, New Jersey
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26
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Stoner N, Stein R. Dietary Therapies for Inflammatory Bowel Disease. PEDIATRIC INFLAMMATORY BOWEL DISEASE 2023:521-537. [DOI: 10.1007/978-3-031-14744-9_37] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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27
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Hu Y, Chen Z, Xu C, Kan S, Chen D. Disturbances of the Gut Microbiota and Microbiota-Derived Metabolites in Inflammatory Bowel Disease. Nutrients 2022; 14:5140. [PMID: 36501169 PMCID: PMC9735443 DOI: 10.3390/nu14235140] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 11/29/2022] [Accepted: 12/01/2022] [Indexed: 12/10/2022] Open
Abstract
Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is characterized as a chronic and recurrent inflammatory disease whose pathogenesis is still elusive. The gut microbiota exerts important and diverse effects on host physiology through maintaining immune balance and generating health-benefiting metabolites. Many studies have demonstrated that IBD is associated with disturbances in the composition and function of the gut microbiota. Both the abundance and diversity of gut microbiota are dramatically decreased in IBD patients. Furthermore, some particular classes of microbiota-derived metabolites, principally short-chain fatty acids, tryptophan, and its metabolites, and bile acids have also been implicated in the pathogenesis of IBD. In this review, we aim to define the disturbance of gut microbiota and the key classes of microbiota-derived metabolites in IBD pathogenesis. In addition, we also focus on scientific evidence on probiotics, not only on the molecular mechanisms underlying the beneficial effects of probiotics on IBD but also the challenges it faces in safe and appropriate application.
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Affiliation(s)
- Yongjia Hu
- School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
- State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
| | - Zhouzhou Chen
- School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
- State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
| | - Chengchen Xu
- School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
- State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
| | - Shidong Kan
- School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
- State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
| | - Daijie Chen
- School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
- State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
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Hasosah M. Consanguinity and Positive Family History of Inflammatory Bowel Diseases in Children: A Multicenter Case–Control Study. JOURNAL OF CHILD SCIENCE 2022. [DOI: 10.1055/s-0042-1757148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
AbstractInflammatory bowel diseases (IBD), which comprise Crohn's disease (CD) and ulcerative colitis (UC), are rising trend in Saudi population. We aim to examine the association between consanguinity and family history and the risk of childhood IBD in Saudi children. A multicenter case–control study conducted in three tertiary hospitals in Jeddah and Riyadh, Saudi Arabia, during periods 2009 to 2021. Data about demographics, consanguinity, family history of IBD, and type of IBD were collected using a structured questionnaire. The same questionnaire was applied in matched case–control. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression analysis that was performed to compare both groups. The study population included 335 children: 167 IBD patients (49.9%) and 168 controls (50.1%). Of these IBD, 93 patients (56%) were CD and 74 patients (44%) were UC. Most of participants were females (72.1%) and their age more than 10 years (51.5%). There was first-degree consanguinity in 66 IBD patients (49.6%). No significant difference in first-degree consanguinity between cases and controls was noted (49.6% in cases vs. 50.4% in controls; OR = 1.02; 95% CI = 0.66–1.57). The consanguinity showed a more significant association with CD than UC (p < 0.05). Family history of IBD (father, siblings, and grandparents) as risk factors for IBD was identified: paternal history of IBD (OR = 0.25, 95% CI = 0.08–0.76), siblings' history of IBD (OR = 2.16, 95% CI = 1.92–2.43), and grandparent's history of IBD (OR = 0.22, 95% CI = 0.07–0.65). Family history of IBD showed a more significant association with CD than UC (p < 0.05). Consanguinity is strongly associated with IBD with more significant association with CD than UC and may possibly explain IBD rise in Saudi Arabia. The greatest risk of family history of IBD is in first-degree relatives, especially in siblings' rather than parents and grandparents.
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Affiliation(s)
- Mohammed Hasosah
- King Saud Bin Abdulaziz, University for Health Sciences, Jeddah, WR, Saudi Arabia
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29
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Telaku S, Veliu A, Sina M, Telaku M, Fejza H, Alidema F. Twin Brothers and a Sister With CD: A Case Report. CLINICAL MEDICINE INSIGHTS: CASE REPORTS 2022; 15:11795476221123537. [PMID: 36091422 PMCID: PMC9452804 DOI: 10.1177/11795476221123537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 08/11/2022] [Indexed: 11/16/2022] Open
Abstract
Crohn’s disease (CD) has an unknown etiology, but it has a genetic component. Many cases of familial CD have been reported. We describe a Kosovar Albanian family with 6 children, of whom 3 have CD: monozygotic twins and their sister. As far as we know, this is the first such report of CD within a Kosovar family.
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Affiliation(s)
| | - Arber Veliu
- CUCK Gastroenterology Department, Pristina, Kosovo
| | - Marsela Sina
- University Hospital Center Mother Theresa University, Tirana, Albania
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30
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Nag D, Farr D, Raychaudhuri S, Withey JH. An adult zebrafish model for adherent-invasive Escherichia coli indicates protection from AIEC infection by probiotic E. coli Nissle. iScience 2022; 25:104572. [PMID: 35769878 PMCID: PMC9234234 DOI: 10.1016/j.isci.2022.104572] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 03/02/2022] [Accepted: 06/06/2022] [Indexed: 12/30/2022] Open
Abstract
Adherent-invasive Escherichia coli (AIEC) is an opportunistic pathogen associated with major inflammatory bowel disease, Crohn disease, and ulcerative colitis. Unfavorable conditions push commensal AIEC to induce gut inflammation, sometimes progressing to inflammation-induced colon cancer. Recently, zebrafish have emerged as a useful model to study human intestinal pathogens. Here, a zebrafish model to study AIEC infection was developed. Bath inoculation with AIEC resulted in colonization and tissue disruption in the zebrafish intestine. Gene expression of pro-inflammatory markers including interleukin-1β (IL-1β), tumor necrosis factor alpha (TNFα), interferon-γ (IFNγ), and S100A-10b (akin to human calprotectin) in the zebrafish intestine was significantly induced by AIEC infection. The probiotic E. coli Nissle 1917 (EcN) was tested as a therapeutic and prophylactic against AIEC infection and reduced AIEC colonization, tissue damage, and pro-inflammatory responses in zebrafish. Furthermore, EcN diminished the propionic-acid-augmented hyperinfection of AIEC in zebrafish. Thus, this study shows the efficacy of EcN against AIEC in an AIEC-zebrafish model.
AIEC can colonize, invade, and induce inflammation in the zebrafish gut Probiotic E. coli Nissle can protect zebrafish from AIEC infection EcN is effective both prophylactically and therapeutically against AIEC-induced IBD
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Affiliation(s)
- Dhrubajyoti Nag
- Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Dustin Farr
- Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Saumya Raychaudhuri
- CSIR-Institute of Microbial Technology, Sector 39A, Chandigarh 160036, India
| | - Jeffrey H. Withey
- Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MI, USA
- Corresponding author
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Sternes PR, Brett L, Phipps J, Ciccia F, Kenna T, de Guzman E, Zimmermann K, Morrison M, Holtmann G, Klingberg E, Mauro D, McIvor C, Forsblad-d'Elia H, Brown MA. Distinctive gut microbiomes of ankylosing spondylitis and inflammatory bowel disease patients suggest differing roles in pathogenesis and correlate with disease activity. Arthritis Res Ther 2022; 24:163. [PMID: 35794662 PMCID: PMC9261041 DOI: 10.1186/s13075-022-02853-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 06/15/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Multiple studies have confirmed dysbiosis in ankylosing spondylitis (AS) and inflammatory bowel disease (IBD); however, due to methodological differences across studies, it has not been possible to determine if these diseases have similar or different gut microbiomes. RESULTS In this study, faecal and intestinal biopsies were obtained from 33 Australian AS patients (including 5 with concomitant IBD, 'AS-IBD'), 59 IBD patients and 105 healthy controls. Stool samples were also obtained from 16 Italian AS patients and 136 Swedish AS patients. Focusing on the Australian cohort, AS, AS-IBD and IBD patients differed from one another and from healthy controls in both alpha and beta diversity. AS patients with and without clinical IBD could be distinguished from one another with moderate accuracy using stool microbiome (AUC=0.754). Stool microbiome also accurately distinguished IBD patients from healthy controls (AUC=0.757). Microbiome composition was correlated with disease activity measured by BASDAI and faecal calprotectin (FCP) levels. Enrichment of potentially pathogenic Streptococcus was noted in AS, AS-IBD and IBD patients. Furthermore, enrichment of another potentially pathogenic genus, Haemophilus, was observed in AS, AS-IBD, IBD, AS patients with increased BASDAI, and IBD patients with faecal calprotectin >100 μg/mg. Apart from these genera, no other taxa were shared between AS and IBD patients. CONCLUSIONS In conclusion, the distinct gut microbiome of AS and AS-IBD patients compared to IBD patients and healthy controls is consistent with immunological and genetic evidence suggesting that the gut plays a different role in driving AS compared with IBD. However, enrichment of two potentially pathogenic genera in both diseases suggests that the presence of a shared/common microbial trigger of disease cannot be discounted.
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Affiliation(s)
- P R Sternes
- Centre for Microbiome Research, Queensland University of Technology, Brisbane, Australia.
| | - L Brett
- Department of Gastroenterology, Logan Hospital, Logan, Australia
| | - J Phipps
- School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia
| | - F Ciccia
- Department of Precision Medicine, Università della Campania L. Vanvitelli, Naples, Italy
| | - T Kenna
- Centre for Microbiome Research, Queensland University of Technology, Brisbane, Australia.,Centre for Immunology and Infection Control, Queensland University of Technology, Brisbane, Australia
| | - E de Guzman
- Centre for Microbiome Research, Queensland University of Technology, Brisbane, Australia.,School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia
| | - K Zimmermann
- Centre for Immunology and Infection Control, Queensland University of Technology, Brisbane, Australia
| | - M Morrison
- School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia
| | - G Holtmann
- Faculty of Health and Behavioural Sciences, University of Queensland, Brisbane, Australia
| | - E Klingberg
- Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - D Mauro
- Department of Precision Medicine, Università della Campania L. Vanvitelli, Naples, Italy
| | - C McIvor
- Department of Gastroenterology, Logan Hospital, Logan, Australia
| | - H Forsblad-d'Elia
- Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - M A Brown
- Genomics England, London, UK.,Faculty of Life Sciences and Medicine, King's College London, London, UK
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32
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Krela-Kaźmierczak I, Zakerska-Banaszak O, Skrzypczak-Zielińska M, Łykowska-Szuber L, Szymczak-Tomczak A, Zawada A, Rychter AM, Ratajczak AE, Skoracka K, Skrzypczak D, Marcinkowska E, Słomski R, Dobrowolska A. Where Do We Stand in the Behavioral Pathogenesis of Inflammatory Bowel Disease? The Western Dietary Pattern and Microbiota-A Narrative Review. Nutrients 2022; 14:nu14122520. [PMID: 35745251 PMCID: PMC9230670 DOI: 10.3390/nu14122520] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 06/13/2022] [Accepted: 06/15/2022] [Indexed: 02/06/2023] Open
Abstract
Despite the increasing knowledge with regard to IBD (inflammatory bowel disease), including ulcerative colitis (UC) and Crohn’s disease (CD), the etiology of these conditions is still not fully understood. Apart from immunological, environmental and nutritional factors, which have already been well documented, it is worthwhile to look at the possible impact of genetic factors, as well as the composition of the microbiota in patients suffering from IBD. New technologies in biochemistry allow to obtain information that can add to the current state of knowledge in IBD etiology.
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Affiliation(s)
- Iwona Krela-Kaźmierczak
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
- Correspondence: (I.K.-K.); (O.Z.-B.); (D.S.)
| | - Oliwia Zakerska-Banaszak
- Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznań, Poland; (M.S.-Z.); (R.S.)
- Correspondence: (I.K.-K.); (O.Z.-B.); (D.S.)
| | | | - Liliana Łykowska-Szuber
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
| | - Aleksandra Szymczak-Tomczak
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
| | - Agnieszka Zawada
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
| | - Anna Maria Rychter
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
- Doctoral School, Poznan University of Medical Sciences, 61-701 Poznań, Poland
| | - Alicja Ewa Ratajczak
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
- Doctoral School, Poznan University of Medical Sciences, 61-701 Poznań, Poland
| | - Kinga Skoracka
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
- Doctoral School, Poznan University of Medical Sciences, 61-701 Poznań, Poland
| | - Dorota Skrzypczak
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
- Correspondence: (I.K.-K.); (O.Z.-B.); (D.S.)
| | - Emilia Marcinkowska
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
| | - Ryszard Słomski
- Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznań, Poland; (M.S.-Z.); (R.S.)
| | - Agnieszka Dobrowolska
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
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33
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Gordon H, Blad W, Trier Møller F, Orchard T, Steel A, Trevelyan G, Ng S, Harbord M. UK IBD Twin Registry: Concordance and Environmental Risk Factors of Twins with IBD. Dig Dis Sci 2022; 67:2444-2450. [PMID: 34097167 DOI: 10.1007/s10620-021-07080-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 05/26/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Twin studies have long been used to infer heritability. Within the 'omics era, twin cohorts have even greater research potential. This study describes the formation of the UK IBD Twin Registry and analysis of concordance and environmental factors. METHOD Twin pairs with IBD were recruited by advertising via IBD charities and social media, re-tracing a dormant IBD database and clinician referral. Details of zygosity, concordance, disease history and environmental factors were assessed. Pair concordance was calculated, and environmental factors were analysed with logistic regression models adjusted for zygosity and concordance. RESULTS Ninety-one twin pairs were included in the analysis; forty-two with CD and forty-nine with UC. More MZ twin pairs with CD were concordant compared with DZ pairs, thus inferring heritability (Chi-sq. 15.6. P < 0.001). In UC, MZ concordance was also numerically greater. Cigarette smoking was predictive of CD (OR 2.66, 95% CI 1.16 to 6.07 P = 0.02); there may be an independent association with cannabis smoking (OR 2.59 95% CI 0.89 to 7.55 P = 0.08). Breastfeeding was protective against UC (OR 0.48, 95% CI 0.25-0.93, P = 0.03), but not CD. Self-reports of less occurrences of gastroenteritis than peers were protective against future UC onset (OR 0.33 95% CI 0.15 to 0.74, P = 0.01). Method of delivery, parental attitudes towards hygiene and recall of diet did not impact future IBD concordance. CONCLUSIONS This study supports the heritability of IBD. Twin study analysis was able to elucidate environmental factors associated with IBD.
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Affiliation(s)
- Hannah Gordon
- Department of Gastroenterology, Royal London Hospital, Whitechapel Rd, Whitechapel, London, E1 1FR, UK.
| | - William Blad
- Department of Gastroenterology, Royal London Hospital, Whitechapel Rd, Whitechapel, London, E1 1FR, UK
| | - Frederik Trier Møller
- Department of Gastroenterology, Royal London Hospital, Whitechapel Rd, Whitechapel, London, E1 1FR, UK
| | - Timothy Orchard
- Department of Gastroenterology, Royal London Hospital, Whitechapel Rd, Whitechapel, London, E1 1FR, UK
| | - Alan Steel
- Department of Gastroenterology, Royal London Hospital, Whitechapel Rd, Whitechapel, London, E1 1FR, UK
| | - Gareth Trevelyan
- Department of Gastroenterology, Royal London Hospital, Whitechapel Rd, Whitechapel, London, E1 1FR, UK
| | - Siew Ng
- Department of Gastroenterology, Royal London Hospital, Whitechapel Rd, Whitechapel, London, E1 1FR, UK
| | - Marcus Harbord
- Department of Gastroenterology, Royal London Hospital, Whitechapel Rd, Whitechapel, London, E1 1FR, UK
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34
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Krovi SH, Kuchroo VK. Activation pathways that drive CD4 + T cells to break tolerance in autoimmune diseases . Immunol Rev 2022;307:161-190. [PMID: 35142369 PMCID: PMC9255211 DOI: 10.1111/imr.13071] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 01/22/2022] [Indexed: 12/11/2022]
Abstract
Autoimmune diseases are characterized by dysfunctional immune systems that misrecognize self as non-self and cause tissue destruction. Several cell types have been implicated in triggering and sustaining disease. Due to a strong association of major histocompatibility complex II (MHC-II) proteins with various autoimmune diseases, CD4+ T lymphocytes have been thoroughly investigated for their roles in dictating disease course. CD4+ T cell activation is a coordinated process that requires three distinct signals: Signal 1, which is mediated by antigen recognition on MHC-II molecules; Signal 2, which boosts signal 1 in a costimulatory manner; and Signal 3, which helps to differentiate the activated cells into functionally relevant subsets. These signals are disrupted during autoimmunity and prompt CD4+ T cells to break tolerance. Herein, we review our current understanding of how each of the three signals plays a role in three different autoimmune diseases and highlight the genetic polymorphisms that predispose individuals to autoimmunity. We also discuss the drawbacks of existing therapies and how they can be addressed to achieve lasting tolerance in patients.
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Affiliation(s)
- Sai Harsha Krovi
- Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
| | - Vijay K Kuchroo
- Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
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35
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Kopper JJ, Iennarella-Servantez C, Jergens AE, Sahoo DK, Guillot E, Bourgois-Mochel A, Martinez MN, Allenspach K, Mochel JP. Harnessing the Biology of Canine Intestinal Organoids to Heighten Understanding of Inflammatory Bowel Disease Pathogenesis and Accelerate Drug Discovery: A One Health Approach. FRONTIERS IN TOXICOLOGY 2022; 3:773953. [PMID: 35295115 PMCID: PMC8915821 DOI: 10.3389/ftox.2021.773953] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 10/07/2021] [Indexed: 12/13/2022] Open
Abstract
In a recent issue of the Lancet, the prevalence of Inflammatory Bowel Disease (IBD) was estimated at 7 million worldwide. Overall, the burden of IBD is rising globally, with direct and indirect healthcare costs ranging between $14.6 and $31.6 billion in the U.S. alone in 2014. There is currently no cure for IBD, and up to 40% of patients do not respond to medical therapy. Although the exact determinants of the disease pathophysiology remain unknown, the prevailing hypothesis involves complex interplay among host genetics, the intestinal microenvironment (primarily bacteria and dietary constituents), and the mucosal immune system. Importantly, multiple chronic diseases leading to high morbidity and mortality in modern western societies, including type II diabetes, IBD and colorectal cancer, have epidemiologically been linked to the consumption of high-calorie, low-fiber, high monosaccharide, and high-fat diets (HFD). More specifically, data from our laboratory and others have shown that repeated consumption of HFD triggers dysbiotic changes of the gut microbiome concomitant with a state of chronic intestinal inflammation and increased intestinal permeability. However, progress in our understanding of the effect of dietary interventions on IBD pathogenesis has been hampered by a lack of relevant animal models. Additionally, current in vitro cell culture systems are unable to emulate the in vivo interplay between the gut microbiome and the intestinal epithelium in a realistic and translatable way. There remains, therefore, a critical need to develop translatable in vitro and in vivo models that faithfully recapitulate human gut-specific physiological functions to facilitate detailed mechanistic studies on the impact of dietary interventions on gut homeostasis. While the study of murine models has been pivotal in advancing genetic and cellular discoveries, these animal systems often lack key clinical signs and temporal pathological changes representative of IBD. Specifically, some limitations of the mouse model are associated with the use of genetic knockouts to induce immune deficiency and disease. This is vastly different from the natural course of IBD developing in immunologically competent hosts, as is the case in humans and dogs. Noteworthily, abundant literature suggests that canine and human IBD share common clinical and molecular features, such that preclinical studies in dogs with naturally occurring IBD present an opportunity to further our understanding on disease pathogenesis and streamline the development of new therapeutic strategies. Using a stepwise approach, in vitro mechanistic studies investigating the contribution of dietary interventions to chronic intestinal inflammation and "gut leakiness" could be performed in intestinal organoids and organoid derived monolayers. The biologic potential of organoids stems from the method's ability to harness hard-wired cellular programming such that the complexity of the disease background can be reflected more accurately. Likewise, the effect of therapeutic drug candidates could be evaluated in organoids prior to longitudinal studies in dog and human patients with IBD. In this review, we will discuss the value (and limitations) of intestinal organoids derived from a spontaneous animal disease model of IBD (i.e., the dog), and how it can heighten understanding of the interplay between dietary interventions, the gut microbiota and intestinal inflammation. We will also review how intestinal organoids could be used to streamline the preclinical development of therapeutic drug candidates for IBD patients and their best four-legged friends.
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Affiliation(s)
- Jamie J Kopper
- Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States.,SMART Translational Medicine, Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States
| | - Chelsea Iennarella-Servantez
- SMART Pharmacology, Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States.,SMART Translational Medicine, Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States
| | - Albert E Jergens
- Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States
| | - Dipak K Sahoo
- Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States.,SMART Translational Medicine, Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States
| | - Emilie Guillot
- 3D Health Solutions, Inc., ISU Research Park, Ames, IA, United States
| | - Agnes Bourgois-Mochel
- Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States
| | - Marilyn N Martinez
- Office of New Animal Drug Evaluation, Center for Veterinary Medicine, Food and Drug Administration, Rockville, MD, United States
| | - Karin Allenspach
- Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States.,SMART Translational Medicine, Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States.,3D Health Solutions, Inc., ISU Research Park, Ames, IA, United States
| | - Jonathan P Mochel
- SMART Pharmacology, Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States.,SMART Translational Medicine, Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States.,3D Health Solutions, Inc., ISU Research Park, Ames, IA, United States
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36
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Boye TL, Steenholdt C, Jensen KB, Nielsen OH. Molecular manipulations and intestinal stem cell-derived organoids in inflammatory bowel disease. Stem Cells 2022; 40:447-457. [DOI: 10.1093/stmcls/sxac014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 02/15/2022] [Indexed: 11/13/2022]
Abstract
Abstract
The pathogenesis of inflammatory bowel diseases (IBD) involves genetic predisposition, environmental factors, and a broadly dysregulated intestinal immune response to the commensal intestinal microflora. The interface between genetic predisposition and environmental factors is reflected in the epigenetic regulation at the transcriptional level. Treatment targets now involve mucosal and histological healing, but the future might additionally include normalization of intestinal cellular functions also at the molecular level, for example comprising complete restoration of phenotypic, genotypic, and epigenetic states. Recent developments in patient-derived epithelial intestinal stem cell (ISC) organoid technologies have opened exciting new therapeutic opportunities to potentially attain molecular healing by combining stem cell therapy with molecular manipulations using (epi)drugs and/or CRISPR/Cas9 genome editing. Here, we are the first to discuss the possibility for phenotypic, genotypic, and epigenetic restoration via molecular manipulations and stem cell therapy in IBD from a clinical perspective.
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Affiliation(s)
- Theresa Louise Boye
- Department of Gastroenterology, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark
| | - Casper Steenholdt
- Department of Gastroenterology, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark
| | - Kim Bak Jensen
- Novo Nordisk Foundation Center for Stem Cell Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen N, Denmark
- Biotech Research and Innovation Centre (BRIC), University of Copenhagen, DK-2200 Copenhagen N, Denmark
| | - Ole Haagen Nielsen
- Department of Gastroenterology, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark
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37
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Correia B, Fernandes J, Botica MJ, Ferreira C, Quintas A. Novel Psychoactive Substances: The Razor's Edge between Therapeutical Potential and Psychoactive Recreational Misuse. MEDICINES (BASEL, SWITZERLAND) 2022; 9:medicines9030019. [PMID: 35323718 PMCID: PMC8950629 DOI: 10.3390/medicines9030019] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 02/23/2022] [Accepted: 02/25/2022] [Indexed: 12/16/2022]
Abstract
BACKGROUND Novel psychoactive substances (NPS) are compounds of natural and synthetic origin, similar to traditional drugs of abuse. NPS are involved in a contemporary trend whose origin lies in a thinner balance between legitimate therapeutic drug research and legislative control. The contemporary NPS trend resulted from the replacement of MDMA by synthetic cathinones in 'ecstasy' during the 2000s. The most common NPS are synthetic cannabinoids and synthetic cathinones. Interestingly, during the last 50 years, these two classes of NPS have been the object of scientific research for a set of health conditions. METHODS Searches were conducted in the online database PubMed using boolean equations. RESULTS Synthetic cannabinoids displayed protective and therapeutic effects for inflammatory, neurodegenerative and oncologic pathologies, activating the immune system and reducing inflammation. Synthetic cathinones act similarly to amphetamine-type stimulants and can be used for depression and chronic fatigue. CONCLUSIONS Despite the scientific advances in this field of research, pharmacological application of NPS is being jeopardized by fatalities associated with their recreational use. This review addresses the scientific achievements of these two classes of NPS and the toxicological data, ending with a reflection on Illicit and NPS control frames.
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Affiliation(s)
- Beatriz Correia
- Laboratório de Ciências Forenses e Psicológicas Egas Moniz, Campus Universitário—Quinta da Granja, Monte de Caparica, 2825-084 Caparica, Portugal; (B.C.); (J.F.); (C.F.)
| | - Joana Fernandes
- Laboratório de Ciências Forenses e Psicológicas Egas Moniz, Campus Universitário—Quinta da Granja, Monte de Caparica, 2825-084 Caparica, Portugal; (B.C.); (J.F.); (C.F.)
| | - Maria João Botica
- Instituto Português de Oncologia de Lisboa Francisco Gentil (IPO), Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal;
| | - Carla Ferreira
- Laboratório de Ciências Forenses e Psicológicas Egas Moniz, Campus Universitário—Quinta da Granja, Monte de Caparica, 2825-084 Caparica, Portugal; (B.C.); (J.F.); (C.F.)
- Molecular Pathology and Forensic Biochemistry Laboratory, Centro de Investigação Interdisciplinar Egas Moniz, 2825-084 Caparica, Portugal
- Faculty of Medicine of Porto University, Rua Professor Lima Basto, 1099-023 Lisboa, Portugal
| | - Alexandre Quintas
- Laboratório de Ciências Forenses e Psicológicas Egas Moniz, Campus Universitário—Quinta da Granja, Monte de Caparica, 2825-084 Caparica, Portugal; (B.C.); (J.F.); (C.F.)
- Molecular Pathology and Forensic Biochemistry Laboratory, Centro de Investigação Interdisciplinar Egas Moniz, 2825-084 Caparica, Portugal
- Correspondence:
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Zhang Z, Yu PF, Gu GL, Zhang YH, Wang YM, Dong ZW, Yang HR. Diffuse invasive signet ring cell carcinoma in total colorectum caused by ulcerative colitis: A case report and review of literature. World J Clin Cases 2022; 10:1729-1737. [PMID: 35211616 PMCID: PMC8855258 DOI: 10.12998/wjcc.v10.i5.1729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 12/05/2021] [Accepted: 12/28/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Diffuse invasive signet ring cell carcinoma of the colorectum is extremely rare clinically. This type of colorectal cancer has certain clinical, pathological and biological characteristics that are different from ordinary colorectal cancer. CASE SUMMARY A 31-year-old young woman was admitted to the hospital for nearly 1 wk due to recurrent symptoms of mucopurulent bloody stools and abdominal distension. Preoperative colonoscopy showed a ring-shaped intestinal wall mass 10 cm from the rectum to the anus. Three pieces of tumor tissue were removed for examination. The pathological results showed rectal mucinous adenocarcinoma. The patient underwent laparoscopic exploration under general anesthesia, and then laparoscopic total colorectal resection, ileal pouch-anal anastomosis and ileostomy were performed. The patient was switched to a FOLFOX + cetuximab regimen. After the fifth cycle, the patient was unable to tolerate further treatment due to tumor progression and multiple organ dysfunction, and died at the end of May 2020. Overall survival was 7 mo. CONCLUSION Carcinogenesis of ulcerative colitis is different from sporadic colon cancer, and the overall prognosis is extremely poor.
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Affiliation(s)
- Zhi Zhang
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
| | - Peng-Fei Yu
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
| | - Guo-Li Gu
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
| | - Yu-Hui Zhang
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
- Graduate School, Hebei North University, Zhangjiakou 075000, Hebei Province, China
| | - Yu-Ming Wang
- Health Team, 93656 Troop of Chinese People's Liberation Army, Beijing 101113, China
| | - Zhi-Wei Dong
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
| | - Hai-Rui Yang
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
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Ogundepo S, Chiamaka AM, Olatinwo M, Adepoju D, Aladesanmi MT, Celestine UO, Ali KC, Umezinwa OJ, Olasore J, Alausa A. The role of diosgenin in crohn’s disease. CLINICAL PHYTOSCIENCE 2022. [DOI: 10.1186/s40816-022-00338-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
AbstractInflammatory bowel disease (IBD) is a chronic idiopathic inflammation that can grossly affect the entire gastrointestinal tract (GIT) from the mouth to the anus. Crohn’s disease is the most known type of IBD and has been the focus of attention due to its increase in prevalence worldwide. Although the etiology is yet to be elucidated, recent studies have pointed out Crohn’s disease to arise from a complex interaction between environmental influences, genetic predisposition, and altered gut microbiota, resulting in dysregulated adaptive and innate responses. The presenting hallmarks of Crohn’s disease may include weight loss, nausea, vomiting, abdominal pain, diarrhea, fever, or chills. Treatment is usually done with many approved immunosuppressive drugs and surgery. However, a promising avenue from natural compounds is a safer therapy due to its safe natural active ingredients and the strong activity it shows in the treatment and management of diseases. Diosgenin, “a major biologically active natural steroidal sapogenin found in Chinese yam,” has been widely reported as a therapeutic agent in the treatment of various classes of disorders such as hyperlipidemia, inflammation, diabetes, cancer, infection, and immunoregulation. In this review, an analysis of literature data on diosgenin employed as a therapeutic agent for the treatment of Crohn’s disease is approached, to strengthen the scientific database and curtail the dreadful impact of Crohn’s disease.
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40
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Ruban M, Slavick A, Amir A, Ben-Tov A, Moran-Lev H, Weintraub Y, Anafy A, Cohen S, Yerushalmy-Feler A. Increasing rate of a positive family history of inflammatory bowel disease (IBD) in pediatric IBD patients. Eur J Pediatr 2022; 181:745-751. [PMID: 34568966 DOI: 10.1007/s00431-021-04269-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 08/21/2021] [Accepted: 09/18/2021] [Indexed: 11/30/2022]
Abstract
The role of a positive family history in pediatric inflammatory bowel disease (IBD) in the era of biologic therapy has not been elucidated. We retrospectively reviewed the medical records of children with IBD and retrieved demographic and clinical characteristics, including the presence of a positive family history of IBD, IBD phenotype, disease course, and therapy. Overall, 325 children (age range at diagnosis 11-15 years) were included, of whom 82 (25.2%) had a positive family history. Children diagnosed during 2016-2020 had a higher frequency of positive family history compared to those diagnosed during 2010-2015 (31.8% versus 20.7%, respectively, p = 0.024). Children with a positive family history had a higher risk for a stricturing phenotype than those with a negative family history (11.3% versus 2.8%, respectively, p = 0.052). They more often received nutritional therapy (53.7% versus 36.6%, p = 0.007) and less often received corticosteroids (36.6% versus 52.7%, p = 0.012). More children with a negative family history needed intensification of biologic therapy (p = 0.041).Conclusion: The rate of a positive family history of IBD in the pediatric IBD population is increasing. A positive family history may have some impact upon IBD phenotype but none on IBD outcome. What is Known: •Familial clustering of inflammatory bowel disease (IBD) has been reported in 5%-15% of IBD patients. •The investigation of the impact of a positive family history upon IBD characteristics and severity revealed conflicting results. What is New: •In this cohort of 325 children with IBD, 25.2% had a positive family history. •The rate of a positive family history of IBD in the pediatric IBD population is increasing. •A positive family history may have some impact upon IBD phenotype but none on IBD outcome.
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Affiliation(s)
- Maya Ruban
- Pediatric Gastroenterology Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, 6423906, Tel Aviv, Israel
| | - Adam Slavick
- Pediatric Gastroenterology Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, 6423906, Tel Aviv, Israel
| | - Achiya Amir
- Pediatric Gastroenterology Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, 6423906, Tel Aviv, Israel
| | - Amir Ben-Tov
- Pediatric Gastroenterology Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, 6423906, Tel Aviv, Israel
| | - Hadar Moran-Lev
- Pediatric Gastroenterology Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, 6423906, Tel Aviv, Israel
| | - Yael Weintraub
- Pediatric Gastroenterology Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, 6423906, Tel Aviv, Israel
| | - Adi Anafy
- Pediatric Gastroenterology Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, 6423906, Tel Aviv, Israel
| | - Shlomi Cohen
- Pediatric Gastroenterology Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, 6423906, Tel Aviv, Israel.
| | - Anat Yerushalmy-Feler
- Pediatric Gastroenterology Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, 6423906, Tel Aviv, Israel
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Snyder EF, Davis S, Aldrich K, Veerabagu M, Larussa T, Abenavoli L, Boccuto L. Crohn disease: Identification, diagnosis, and clinical management. Nurse Pract 2021; 46:22-30. [PMID: 34808643 DOI: 10.1097/01.npr.0000798212.61425.4f] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
ABSTRACT Crohn disease is an inflammatory bowel disorder affecting children and adults. With its increasing prevalence, healthcare providers need adequate resources to assist with diagnosis and management. This article discusses early diagnosis, disease severity and classification, familial predisposition and genomics, and clinical management in the primary care setting.
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Malibary NH, Ezzat MA, Mogharbel AM, Kouzaba KA, Alkadi AA, Malki UH, Gharib SM, Altowairqi FM, Saadah OI, Mosli MH. Factors Affecting Ulcerative Colitis Flare-Ups: Associations With Smoking Habits and Other Patient Characteristics. Cureus 2021; 13:e19834. [PMID: 34824952 PMCID: PMC8610210 DOI: 10.7759/cureus.19834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/23/2021] [Indexed: 12/03/2022] Open
Abstract
Background and study aims Currently, there are no studies conducted in the Kingdom of Saudi Arabia (KSA) that have assessed the relationship between ulcerative colitis (UC) flare-ups and smoking. The present study aims to assess the risk of UC flare-ups and evaluate the relationship between UC flare-ups and smoking in adult patients following up at King Abdulaziz University Hospital in Jeddah, KSA. Patients and methods This was a retrospective study involving patients with confirmed UC between January 2015 and December 2020. Various information was examined, including demographic, clinical, endoscopic, radiologic, and laboratory data. Descriptive statistics were used for summarizing findings and a logistic regression analysis was applied to test for possible associations. Results Eighty-nine patients with UC were included in the study. Almost half (48.3%) had recurrent UC flare-ups during follow-up. A non-significant relationship was found between recurrent UC flares and all types of smoking habits (cigarette smoking, P = 0.15; shisha smoking, P = 0.88; and vape smoking, P = 0.09). Participants who were underweight (P = 0.041), had family history of UC (P = 0.013), depression (P = 0.033), fecal incontinence (P = 0.003), iron deficiency anemia (P = 0.009), or a malignancy (P = 0.039) had a significantly higher probability of experiencing recurrent flares. Binary logistic regressions revealed that family history of UC (OR = 5.3, P = 0.007) and fecal incontinence (OR = 4.7, P = 0.006) were associated significantly with recurrent flares. Conclusion There was no clear association between smoking and recurrent UC flares identified in this cohort. Of the variables considered, UC patients with fecal incontinence or family history of UC were at the highest risk of developing recurrent flares.
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Affiliation(s)
- Nadim H Malibary
- Visceral and General Surgery, Hautepierre Hospital, Strasbourg, FRA.,Surgery, King Abdulaziz University Hospital, Jeddah, SAU
| | | | | | | | | | - Usama H Malki
- Medicine, King Abdulaziz University Hospital, Jeddah, SAU
| | | | | | - Omar I Saadah
- Pediatric Gastroenterology, King Abdulaziz University Hospital, Jeddah, SAU
| | - Mahmoud H Mosli
- Gastroenterology, King Abdulaziz University Hospital, Jeddah, SAU
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Yao L, Guo J, Gui J, Bai F, Xin R, Deng Y, Wang S, Li H. ICOS + follicular regulatory T cells are implicated in the pathogenesis of ulcerative colitis. Clin Exp Pharmacol Physiol 2021; 48:1566-1575. [PMID: 34363223 DOI: 10.1111/1440-1681.13568] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 08/03/2021] [Accepted: 08/04/2021] [Indexed: 01/14/2023]
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) with a rising incidence worldwide. The precise aetiology is unclear, but aberrant regulatory T cell (Treg) responses have been documented in active UC patients. Follicular regulatory T cell (Tfr) is a recently identified subset of Treg cells. In this study, the role of ICOS in Tfr cells, which is a costimulatory molecule shown to stabilize and promote Treg differentiation, was investigated in UC patients. We found that with increasing UC severity, the frequency of ICOS+ CD4 T cells was increased, but the level of ICOS expression by ICOS+ CD4 T cells was decreased. ICOS+ cells were highly enriched in follicular regulatory T cells (Tfr), which is a subset of Treg cells characterized by CD25+ CD127- CXCR5+ Foxp3+ phenotype. Anti-CD3, anti-CD3/CD28, or anti-CD3/ICOS had all significantly increased the expression of Foxp3 and IL-10, and among the three stimulation methods, anti-CD3/ICOS was most effective at enhancing Foxp3 and IL-10 expression. Moreover, anti-CD3/ICOS-stimulated Tfr cells could suppress conventional T cell proliferation in an IL-10-dependent manner. Interestingly, anti-CD3/ICOS stimulation was less effective in UC-Mild and UC-Active patients compared to that in healthy and UC-Remission patients. In addition, UC patients presented impairment in ICOS upregulation following anti-CD3 stimulation. Overall, these data indicated that ICOS+ Tfr cells were dysregulated in UC patients and the level of dysregulation was associated with the severity of UC, suggesting that ICOS+ Tfr cells could serve as a biomarker of the progression of UC.
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Affiliation(s)
- Li Yao
- Department of Gastroenterology, Ningxia People's Hospital, The First Affiliated Hospital of Northwest Minzu University, Yinchuan, China
| | - Jianyang Guo
- Department of Gastroenterology, Ningxia People's Hospital, The First Affiliated Hospital of Northwest Minzu University, Yinchuan, China
| | - Juan Gui
- Department of Gynaecology and Obstetrics, Yinchuan Hospital of Traditional Chinese Medicine, Yinchuan, China
| | - Feihu Bai
- Department of Gastroenterology, Ningxia People's Hospital, The First Affiliated Hospital of Northwest Minzu University, Yinchuan, China
| | - Ruijuan Xin
- Department of Gastroenterology, Ningxia People's Hospital, The First Affiliated Hospital of Northwest Minzu University, Yinchuan, China
| | - Yanhong Deng
- Department of Gastroenterology, Ningxia People's Hospital, The First Affiliated Hospital of Northwest Minzu University, Yinchuan, China
| | - Shaoxuan Wang
- Department of Gastroenterology, Jining No.1 People's Hospital, Jining, China
| | - Haitao Li
- Department of Urology, The First Affiliated Hospital of Northwest Minzu University Ningxia People's Hospital, Yinchuan, China
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Pierre N, Salée C, Vieujean S, Bequet E, Merli AM, Siegmund B, Meuwis MA, Louis E. Review article: distinctions between ileal and colonic Crohn's disease: from physiology to pathology. Aliment Pharmacol Ther 2021; 54:779-791. [PMID: 34297423 DOI: 10.1111/apt.16536] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 05/15/2021] [Accepted: 07/05/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Ileal and colonic Crohn's disease seem to be two separate entities. AIMS To describe the main physiological distinctions between the small and the large intestine and to analyse the differences between ileal and colonic Crohn's disease. METHODS The relevant literature was critically examined and synthesised. RESULTS The small and large intestine have fundamental distinctions (anatomy, cellular populations, immune defence, microbiota). The differences between ileal and colonic Crohn's disease are highlighted by a heterogeneous body of evidence including clinical features (natural history of the disease, efficacy of treatments, and monitoring), epidemiological data (smoking status, age, gender) and biological data (genetics, microbiota, immunity, mesenteric fat). However, the contribution of these factors to disease location remains poorly understood. CONCLUSION The classification of ileal and colonic Crohn's disease as distinct subphenotypes is well supported by the literature. Understanding of these differences could be exploited to develop more individualised patient care.
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Affiliation(s)
- Nicolas Pierre
- Laboratory of Translational Gastroenterology, GIGA-Institute, University of Liège, Liège, Belgium
| | - Catherine Salée
- Laboratory of Translational Gastroenterology, GIGA-Institute, University of Liège, Liège, Belgium
| | - Sophie Vieujean
- Laboratory of Translational Gastroenterology, GIGA-Institute, University of Liège, Liège, Belgium.,Hepato-Gastroenterology and Digestive Oncology Department, Liège University Hospital, Liège, Belgium
| | - Emeline Bequet
- Laboratory of Translational Gastroenterology, GIGA-Institute, University of Liège, Liège, Belgium.,Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Liège University Hospital, Liège, Belgium
| | - Angela-Maria Merli
- Laboratory of Translational Gastroenterology, GIGA-Institute, University of Liège, Liège, Belgium
| | - Britta Siegmund
- Division of Gastroenterology, Infectiology and Rheumatology, Medical Department, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - Marie-Alice Meuwis
- Laboratory of Translational Gastroenterology, GIGA-Institute, University of Liège, Liège, Belgium.,Hepato-Gastroenterology and Digestive Oncology Department, Liège University Hospital, Liège, Belgium
| | - Edouard Louis
- Laboratory of Translational Gastroenterology, GIGA-Institute, University of Liège, Liège, Belgium.,Hepato-Gastroenterology and Digestive Oncology Department, Liège University Hospital, Liège, Belgium
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Jergens AE, Parvinroo S, Kopper J, Wannemuehler MJ. Rules of Engagement: Epithelial-Microbe Interactions and Inflammatory Bowel Disease. Front Med (Lausanne) 2021; 8:669913. [PMID: 34513862 PMCID: PMC8432614 DOI: 10.3389/fmed.2021.669913] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 08/05/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex, multifactorial disorders that lead to chronic and relapsing intestinal inflammation. The exact etiology remains unknown, however multiple factors including the environment, genetic, dietary, mucosal immunity, and altered microbiome structure and function play important roles in disease onset and progression. Supporting this notion that the gut microbiota plays a pivotal role in IBD pathogenesis, studies in gnotobiotic mice have shown that mouse models of intestinal inflammation require a microbial community to develop colitis. Additionally, antimicrobial therapy in some IBD patients will temporarily induce remission further demonstrating an association between gut microbes and intestinal inflammation. Finally, a dysfunctional intestinal epithelial barrier is also recognized as a key pathogenic factor in IBD. The intestinal epithelium serves as a barrier between the luminal environment and the mucosal immune system and guards against harmful molecules and microorganisms while being permeable to essential nutrients and solutes. Beneficial (i.e., mutualists) bacteria promote mucosal health by strengthening barrier integrity, increasing local defenses (mucin and IgA production) and inhibiting pro-inflammatory immune responses and apoptosis to promote mucosal homeostasis. In contrast, pathogenic bacteria and pathobionts suppress expression and localization of tight junction proteins, cause dysregulation of apoptosis/proliferation and increase pro-inflammatory signaling that directly damages the intestinal mucosa. This review article will focus on the role of intestinal epithelial cells (IECs) and the luminal environment acting as mediators of barrier function in IBD. We will also share some of our translational observations of interactions between IECs, immune cells, and environmental factors contributing to maintenance of mucosal homeostasis, as it relates to GI inflammation and IBD in different animal models.
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Affiliation(s)
- Albert E. Jergens
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - Shadi Parvinroo
- Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - Jamie Kopper
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - Michael J. Wannemuehler
- Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
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Miller MO, Kashyap PC, Becker SL, Thomas RM, Hodin RA, Miller G, Hundeyin M, Pushalkar S, Cohen D, Saxena D, Shogan BD, Morris-Stiff GJ. SSAT State-of-the-Art Conference: Advancements in the Microbiome. J Gastrointest Surg 2021; 25:1885-1895. [PMID: 32989690 DOI: 10.1007/s11605-020-04551-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The microbiome plays a major role in human physiology by influencing obesity, inducing inflammation, and impacting cancer therapies. During the 60th Annual Meeting of the Society of the Alimentary Tract (SSAT) at the State-of-the-Art Conference, experts in the field discussed the influence of the microbiome. This paper is a summary of the influence of the microbiome on obesity, inflammatory bowel disease, pancreatic cancer, cancer therapies, and gastrointestinal optimization. This review shows how the microbiome plays an important role in the development of diseases and surgical complications. Future studies are needed in targeting the gut microbiome to develop individualized therapies.
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Affiliation(s)
- Miquell O Miller
- Department of General Surgery, Stanford University, 300 Pasteur Dr, Stanford, CA, 94305, USA.
| | - Purna C Kashyap
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Sarah L Becker
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Ryan M Thomas
- Departments of Surgery, Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, 32610, USA
| | - Richard A Hodin
- Department of Surgery, Massachusetts General Hospital, Boston, MA, 02114, USA
| | - George Miller
- Departments of Surgery and Cell Biology, New York University School of Medicine, New York, NY, 10016, USA
| | - Mautin Hundeyin
- Departments of Surgery and Cell Biology, New York University School of Medicine, New York, NY, 10016, USA
| | - Smruti Pushalkar
- Department of Medicine, New York University School of Medicine, New York, NY, 10016, USA
| | - Deirdre Cohen
- Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY, 10010, USA
| | - Deepak Saxena
- Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY, 10010, USA
| | - Benjamin D Shogan
- Department of Surgery, University of Chicago, Chicago, IL, 60637, USA
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Jung H, Kim JS, Lee KH, Tizaoui K, Terrazzino S, Cargnin S, Smith L, Koyanagi A, Jacob L, Li H, Hong SH, Yon DK, Lee SW, Kim MS, Wasuwanich P, Karnsakul W, Shin JI, Kronbichler A. Roles of microRNAs in inflammatory bowel disease. Int J Biol Sci 2021; 17:2112-2123. [PMID: 34131410 PMCID: PMC8193269 DOI: 10.7150/ijbs.59904] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 05/08/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract that mainly affects young people. IBD is associated with various gastrointestinal symptoms, and thus, affects the quality of life of patients. Currently, the pathogenesis of IBD is poorly understood. Although intestinal bacteria and host immune response are thought to be major factors in its pathogenesis, a sufficient explanation of their role in its pathophysiologic mechanism has not been presented. MicroRNAs (miRNAs), which are small RNA molecules that regulate gene expression, have gained attention as they are known to participate in the molecular interactions of IBD. Recent studies have confirmed the important role of miRNAs in targeting certain molecules in signaling pathways that regulate the homeostasis of the intestinal barrier, inflammatory reactions, and autophagy of the intestinal epithelium. Several studies have identified the specific miRNAs associated with IBD from colon tissues or serum samples of IBD patients and have attempted to use them as useful diagnostic biomarkers. Furthermore, some studies have attempted to treat IBD through intracolonic administration of specific miRNAs in the form of nanoparticle. This review summarizes the latest findings on the role of miRNAs in the pathogenesis, diagnosis, and treatment of IBD.
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Affiliation(s)
- HyunTaek Jung
- Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jae Seok Kim
- Department of Nephrology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Keum Hwa Lee
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kalthoum Tizaoui
- Laboratory Microorganisms and Active Biomolecules, Sciences Faculty of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Salvatore Terrazzino
- Department of Pharmaceutical Sciences and Interdepartmental Research Center of Pharmacogenetics and Pharmacogenomics (CRIFF), University of Piemonte Orientale, Novara, Italy
| | - Sarah Cargnin
- Department of Pharmaceutical Sciences and Interdepartmental Research Center of Pharmacogenetics and Pharmacogenomics (CRIFF), University of Piemonte Orientale, Novara, Italy
| | - Lee Smith
- The Cambridge Centre for Sport and Exercise Science, Anglia Ruskin University, Cambridge, CB1 1PT, UK
| | - Ai Koyanagi
- Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, 08830 Barcelona, Spain.,ICREA, Pg. Lluis Companys 23, 08010 Barcelona, Spain
| | - Louis Jacob
- Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, 08830 Barcelona, Spain.,Faculty of Medicine, University of Versailles Saint-Quentin-en-Yvelines, 78000 Versailles, France
| | - Han Li
- University of Florida College of Medicine, Gainesville, FL 32610, USA
| | - Sung Hwi Hong
- Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Dong Keon Yon
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Seung Won Lee
- Department of Data Science, Sejong University College of Software Convergence, Seoul, Republic of Korea
| | - Min Seo Kim
- Korea University, College of Medicine, Seoul, Republic of Korea
| | - Paul Wasuwanich
- University of Florida College of Medicine, Gainesville, FL 32610, USA
| | - Wikrom Karnsakul
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Jae Il Shin
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Andreas Kronbichler
- Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria
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48
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Kitani T, Maddipatla SC, Madupuri R, Greco C, Hartmann J, Baraniuk JN, Vasudevan S. In Search of Newer Targets for Inflammatory Bowel Disease: A Systems and a Network Medicine Approach. NETWORK AND SYSTEMS MEDICINE 2021. [DOI: 10.1089/nsm.2020.0012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Takashi Kitani
- Department of Neurology, Molecular and Cellular Biology, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Sushma C. Maddipatla
- Department of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Ramya Madupuri
- Department of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Christopher Greco
- Department of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Jonathan Hartmann
- Dahlgren Memorial Library, Graduate Health and Life Sciences Research Library, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - James N. Baraniuk
- Division of Rheumatology, Immunology and Allergy, Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Sona Vasudevan
- Department of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, Washington, District of Columbia, USA
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49
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Villanacci V, Reggiani-Bonetti L, Salviato T, Leoncini G, Cadei M, Albarello L, Caputo A, Aquilano MC, Battista S, Parente P. Histopathology of IBD Colitis. A practical approach from the pathologists of the Italian Group for the study of the gastrointestinal tract (GIPAD). Pathologica 2021; 113:39-53. [PMID: 33686309 PMCID: PMC8138698 DOI: 10.32074/1591-951x-235] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 12/03/2020] [Indexed: 12/13/2022] Open
Abstract
Inflammatory bowel diseases (IBDs) are lifelong disorders in which an interaction between genetic and environmental factors is involved. IBDs include two entities: Crohn's disease (CD) and ulcerative colitis (UC); these can be adequately diagnosed and distinguished with a correct methodological approach based on communicating exhaustive clinical, endoscopic and laboratory information to the pathologist and performing adequate bioptic sampling and precise morphological signs including crypt architecture, distribution of inflammation and granulomas, when present. IBD needs to be distinguished from non-IBD colitis, mostly at its onset. Moreover, IBDs are associated with an increased risk of developing colorectal adenocarcinoma. In daily pathological practice, correct diagnosis of IBD and its subclassification as well as a correct detection of dysplasia is imperative to establish the best therapeutic approach.
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Affiliation(s)
- Vincenzo Villanacci
- Institute of Pathology, Spedali Civili, Brescia, Italy
- Correspondence Vincenzo Villanacci Institute of Pathology Spedali Civili, Brescia, Italy E-mail:
| | - Luca Reggiani-Bonetti
- Department of Diagnostic, Clinic and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Tiziana Salviato
- Department of Diagnostic, Clinic and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | | | - Moris Cadei
- Institute of Pathology, Spedali Civili, Brescia, Italy
| | - Luca Albarello
- Pathology Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy
| | - Alessandro Caputo
- University Hospital “San Giovanni di Dio e Ruggi D’Aragona”, Salerno, Italy
| | | | - Serena Battista
- Institute of Pathology S. Maria della Misericordia Hospital, Udine, Italy
| | - Paola Parente
- Unit of Pathology, Fondazione IRCCS Ospedale Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), Italy
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50
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Hemida M, Vuori KA, Moore R, Anturaniemi J, Hielm-Björkman A. Early Life Modifiable Exposures and Their Association With Owner Reported Inflammatory Bowel Disease Symptoms in Adult Dogs. Front Vet Sci 2021; 8:552350. [PMID: 33598486 PMCID: PMC7882719 DOI: 10.3389/fvets.2021.552350] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 01/04/2021] [Indexed: 12/04/2022] Open
Abstract
Background: Inflammatory bowel disease (IBD) is an idiopathic multifactorial disease in humans and dogs, usually assigned to the interactions between genes, gut microbiota, diet, environment, and the immune system. We aimed to investigate the modifiable early life exposures associated with IBD in dogs. Materials and Methods: The study data was extracted from the validated owner-reported DogRisk food frequency questionnaire. This was a cross-sectional questionnaire-based study that tested 21 different early life dietary and environmental, demographic and genetic variables for their association with IBD or not, in adult dogs. A total of 7,015 dogs participated in this study. The study covered early life periods; prenatal, neonatal, early, and late postnatal periods. Two feeding patterns, a non-processed meat-based diet (NPMD) and an ultra-processed carbohydrate-based diet (UPCD) were studied. Data was analyzed using logistic regression analysis with a backward stepwise deletion. Results: From the final models we found that the NPMD during early and late postnatal periods were significantly associated with lower IBD risk later in life. The UPCD during the same periods was associated with a higher risk of IBD incidence. Also, the maternal diet during the neonatal period showed a non-significant trend of lower IBD risk in the offspring with the NPMD and a higher IBD risk with the UPCD. Additionally, the normal body weight of puppies during the first 6 months of age was associated with a lower risk of IBD in adulthood while, slim puppies associated significantly with IBD in adulthood. From the non-modifiable background variables, we identified the maternal history of IBD as the strongest risk factor for later incidence of IBD. Furthermore, male dogs were twice as likely to develop IBD as female dogs were. Conclusions: It is reassuring for owners to know that they themselves can have an impact on their dog's health. A high-fat, low-carbohydrate NPMD exposure during early life, and a normal body condition in puppyhood were significantly associated with less IBD in adult dogs. The opposite was true for UPCD exposure and abnormal body condition score in 6 month old puppies.
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Affiliation(s)
- Manal Hemida
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.,Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Kristiina A Vuori
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Robin Moore
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Johanna Anturaniemi
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Anna Hielm-Björkman
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
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