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Kafentzi T, Tsounis EP, Tourkochristou E, Avramopoulou E, Aggeletopoulou I, Geramoutsos G, Sotiropoulos C, Pastras P, Thomopoulos K, Theocharis G, Triantos C. Genetic Polymorphisms (ApaI, FokI, BsmI, and TaqI) of the Vitamin D Receptor (VDR) Influence the Natural History and Phenotype of Crohn's Disease. Int J Mol Sci 2025; 26:1848. [PMID: 40076474 PMCID: PMC11899612 DOI: 10.3390/ijms26051848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 02/14/2025] [Accepted: 02/19/2025] [Indexed: 03/14/2025] Open
Abstract
Vitamin D receptor (VDR) single-nucleotide polymorphisms (SNPs) modulate vitamin D/VDR signaling, a key pathway in inflammatory bowel disease (IBD) pathogenesis. This study investigates how ApaI, BsmI, TaqI, and FokI SNPs affect IBD phenotype and progression. A total of 76 Crohn's disease (CD) and 68 ulcerative colitis (UC) patients were genotyped. On initial bivariate analysis, the AA genotype of ApaI was accompanied by higher rates of penetrating (B3) CD (36.7% vs. 8.7%; p = 0.012). The FokI SNP was associated with disease location, with the ff genotype predisposing to CD and affecting the upper GI (36.4% vs. 7.7%; p = 0.044) or the colon (90.9% vs. 50.8%; p = 0.038). Moreover, patients harboring the ApaI A allele (AA/Aa) experienced higher rates of steroid-refractory or steroid-dependent CD. In multivariate analyses, the aa genotype showed a protective effect against hospitalization (aOR = 0.17; p = 0.013) in CD, whereas the TT genotype emerged as an independent risk factor (aOR = 4.79; p = 0.044). Moreover, the aa genotype was independently associated with a decreased risk of IBD-related surgery (aOR = 0.055; p = 0.014). VDR SNPs, particularly ApaI, influence disease phenotype, progression, and treatment response in CD. The aa genotype of ApaI appears to confer protection against adverse disease outcomes.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece; (T.K.); (E.P.T.); (E.T.); (E.A.); (I.A.); (G.G.); (C.S.); (P.P.); (K.T.); (G.T.)
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Huang Z, Yuan W. Exploring genetic structures and shared sites between alcohol, cheese intake, and inflammatory bowel disease. Front Nutr 2025; 12:1468457. [PMID: 39917747 PMCID: PMC11798781 DOI: 10.3389/fnut.2025.1468457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 01/09/2025] [Indexed: 02/09/2025] Open
Abstract
Background An association has been observed between alcohol and cheese intake and the onset of inflammatory bowel disease (IBD), necessitating further exploration from a genetic structural perspective. Methods The present analysis was focused on the intake of alcohol and cheese in conjunction with IBD genome-wide association study (GWAS) data, with the objective of exploring genetic correlations and identifying common loci. Initially, overall genetic correlations were assessed employing two methodologies: linkage disequilibrium score regression (LDSC) and genetic covariance analyzer (GNOVA). Subsequently, local correlations were examined through the SUPERGNOVA method. A genetic overlap analysis between various traits was then conducted based on the statistical theory of conditional/conjunctional false discovery rate (cond/conjFDR). Ultimately, shared loci between the two traits were identified via conjFDR analysis and multi-trait analysis of GWAS (MTAG). Results Substantial overall correlations were noted at the genome-wide level between alcohol and cheese intake and both IBD and Crohn's disease (CD), whereas the association with ulcerative colitis (UC) was of lesser significance. In the local genetic analysis, chromosome 16 emerged as a key region implicated in the relationship between alcohol and cheese intake and IBD (including both CD and UC). The conjFDR analysis confirmed the genetic overlap between the two diseases. Furthermore, both conjFDR and MTAG analyses identified multiple shared genetic loci, with nine genes (Y_RNA, DENND1B, GCKR, KPNA7, CLN3, SLC39A8, FUT2, ERAP2, and SMAD3) being. Conclusion The present study provides genetic evidence supporting the comorbidity of alcohol and cheese intake with IBD, offering novel insights into potential strategies for the prevention and treatment of IBD through the modulation of alcohol and cheese consumption.
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Affiliation(s)
- Zhifang Huang
- Department of Anorectal Surgery, Jiangmen Wuyi Hospital of Traditional Chinese Medicine, Jiangmen, China
| | - Weichao Yuan
- Department of Anorectal Surgery, Affiliated Hospital of Jiujiang University, Jiujiang, China
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Farid MS, Shafique B, Xu R, Łopusiewicz Ł, Zhao C. Potential interventions and interactions of bioactive polyphenols and functional polysaccharides to alleviate inflammatory bowel disease - A review. Food Chem 2025; 462:140951. [PMID: 39213975 DOI: 10.1016/j.foodchem.2024.140951] [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: 04/25/2024] [Revised: 08/17/2024] [Accepted: 08/20/2024] [Indexed: 09/04/2024]
Abstract
Inflammatory bowel disease is a multifaceted condition that is influenced by nutritional, microbial, environmental, genetic, psychological, and immunological factors. Polyphenols and polysaccharides have gained recognition for their therapeutic potential. This review emphasizes the biological effects of polyphenols and polysaccharides, and explores their antioxidant, anti-inflammatory, and microbiome-modulating properties in the management of inflammatory bowel disease (IBD). However, polyphenols encounter challenges, such as low stability and low bioavailability in the colon during IBD treatment. Hence, polysaccharide-based encapsulation is a promising solution to achieve targeted delivery, improved bioavailability, reduced toxicity, and enhanced stability. This review also discusses the significance of covalent and non-covalent interactions, and simple and complex encapsulation between polyphenols and polysaccharides. The administration of these compounds in appropriate quantities has proven beneficial in preventing the development of Crohn's disease and ulcerative colitis, ultimately leading to the management of IBD. The use of polyphenols and polysaccharides has been found to reduce histological scores and colon injury associated with IBD, increase the abundance of beneficial microbes, inhibit the development of colitis-associated cancer, promote the production of microbial end-products, such as short-chain fatty acids (SCFAs), and improve anti-inflammatory properties. Despite the combined effects of polyphenols and polysaccharides observed in both in vitro and in vivo studies, further human clinical trials are needed to comprehend their effectiveness on inflammatory bowel disease.
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Affiliation(s)
| | - Bakhtawar Shafique
- College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China
| | - Rui Xu
- College of Food Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao 066004, China
| | - Łukasz Łopusiewicz
- School of Medical & Health Sciences, University of Economics and Human Sciences in Warsaw, 59 Okopowa Str. Warszawa, 01-043, Poland; Institute of Pharmacy, Department Pharmaceutical Biology, Greifswald University, Friedrich-Ludwig-Jahn-Str. 17, 17489 Greifswald, Germany
| | - Changhui Zhao
- College of Food Science and Engineering, Jilin University, Changchun 130062, China.
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Hasnaoui A, Trigui R, Giuffrida M. Gut microbiota and mesenteric adipose tissue interactions in shaping phenotypes and treatment strategies for Crohn's disease. World J Gastroenterol 2024; 30:4969-4976. [PMID: 39679306 PMCID: PMC11612712 DOI: 10.3748/wjg.v30.i46.4969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 10/03/2024] [Accepted: 10/29/2024] [Indexed: 11/21/2024] Open
Abstract
In this letter, we commented on the article by Wu et al. We examined the interactions between mesenteric adipose tissue, creeping fat, and gut microbiota in Crohn's disease (CD), a condition marked by chronic gastrointestinal inflammation with a rising global incidence. The pathogenesis of CD involves complex genetic, environmental, and microbial factors. Dysbiosis, which is an imbalance in gut microbial communities, is frequently observed in CD patients, highlighting the pivotal role of the gut microbiota in disease progression and the inflammatory response. Recent studies have shown that mesenteric adipose tissue and creeping fat actively contribute to inflammation by producing proinflammatory cytokines. The relationship between creeping fat and altered microbiota can shift from a potentially protective role to one that encourages bacterial translocation, further complicating disease management. Recent research has suggested that fecal microbiota transplantation could help restore microbial balance, offering a promising therapeutic strategy to improve clinical disease response.
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Affiliation(s)
- Anis Hasnaoui
- Faculty of Medicine of Tunis, Tunis El Manar University, Bab Saadoun Tunis 1007, Tunisia
- Department of General Surgery, Menzel Bourguiba Hospital, Menzel Bourguiba 7050, Bizerte, Tunisia
| | - Racem Trigui
- Department of General Surgery, Menzel Bourguiba Hospital, Menzel Bourguiba 7050, Bizerte, Tunisia
| | - Mario Giuffrida
- Department of General Surgery, Guglielmo da Saliceto Hospital, Piacenza 29100, Italy
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Shaban SF, Abdel-Fattah EA, Ali MM, Dessouky AA. The therapeutic efficacy of adipose mesenchymal stem cell-derived microvesicles versus infliximab in a dextran sodium sulfate induced ulcerative colitis rat model. Ultrastruct Pathol 2024; 48:526-549. [PMID: 39545690 DOI: 10.1080/01913123.2024.2426566] [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: 08/18/2024] [Revised: 10/25/2024] [Accepted: 11/04/2024] [Indexed: 11/17/2024]
Abstract
Ulcerative colitis (UC) is a chronic relapsing intestinal inflammation that is becoming of increasing incidence worldwide and has insufficient treatment. Therefore, finding effective therapies remains a priority. A dextran sodium sulfate colitis model was established to elucidate colonic layers alterations and compare adipose mesenchymal stem cell-derived microvesicles (MSC-MVs) versus infliximab (IFX) efficacy through biochemical, light, and electron microscope studies. Fifty-four rats were allocated to 4 groups: Control (Con), UC, UC+IFX, and UC+MSC-MVs groups. End body weights (BW) and serum malondialdehyde (MDA) levels were recorded. Colitis severity was estimated by disease activity index (DAI). Colonic specimens were processed to evaluate the histological structure, collagen content, surface mucous and goblet cells, CD44, TNF-α, and GFAP immune expression. Morphometric and statistical analyses were performed. The UC group revealed congested, stenosed colons, a significant decline in end BW, and a significant increase in serum MDA and DAI. Furthermore, disturbed histoarchitecture, inflammatory infiltration, depletion of surface mucous and goblet cells, increased collagen, and TNF-α expression and decreased GFAP expression were observed. Alterations were partially attenuated by IFX therapy, whereas MSC-MVs significantly improved all parameters. In conclusion, MSC-MVs were a superior therapeutic option, via attenuating oxidative stress and inflammatory infiltration, in addition to restoring intestinal epithelial integrity and mucosal barrier.
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Affiliation(s)
- Sahar F Shaban
- Department of Medical Histology and Cell Biology, Medicine, Faculty of medicine, Zagazig University, Zagazig city, Egypt
| | - Eman A Abdel-Fattah
- Department of Medical Histology and Cell Biology, Medicine, Faculty of medicine, Zagazig University, Zagazig city, Egypt
| | - Manar M Ali
- Department of Medical Histology and Cell Biology, Medicine, Faculty of medicine, Zagazig University, Zagazig city, Egypt
| | - Arigue A Dessouky
- Department of Medical Histology and Cell Biology, Medicine, Faculty of medicine, Zagazig University, Zagazig city, Egypt
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Cheng WW, Liu BH, Hou XT, Meng H, Wang D, Zhang CH, Yuan S, Zhang QG. Natural Products on Inflammatory Bowel Disease: Role of Gut Microbes. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2024; 52:1275-1301. [PMID: 39192679 DOI: 10.1142/s0192415x24500514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/29/2024]
Abstract
Inflammatory bowel disease (IBD) refers to long-term medical conditions that involve inflammation of the digestive tract, and the global incidence and prevalence of IBD are on the rise. Gut microbes play an important role in maintaining the intestinal health of the host, and the occurrence, development, and therapeutic effects of IBD are closely related to the structural and functional changes of gut microbes. Published studies have shown that the natural products from traditional Chinese medicine have direct or indirect regulatory impacts on the composition and metabolism of the gut microbes. In this review, we summarize the research progress of several groups of natural products, i.e., flavonoids, alkaloids, saponins, polysaccharides, polyphenols, and terpenoids, for the therapeutic activities in relieving IBD symptoms. The role of gut microbes and their intestinal metabolites in managing the IBD is presented, with focusing on the mechanism of action of those natural products. Traditional Chinese medicine alleviated IBD symptoms by regulating gut microbes, providing important theoretical and practical basis for the treatment of variable inflammatory intestinal diseases.
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Affiliation(s)
- Wen-Wen Cheng
- Chronic Diseases Research Center, Dalian University College of Medicine, Dalian, Liaoning 116622, P. R. China
| | - Bao-Hong Liu
- Chronic Diseases Research Center, Dalian University College of Medicine, Dalian, Liaoning 116622, P. R. China
| | - Xiao-Ting Hou
- Chronic Diseases Research Center, Dalian University College of Medicine, Dalian, Liaoning 116622, P. R. China
| | - Huan Meng
- Chronic Diseases Research Center, Dalian University College of Medicine, Dalian, Liaoning 116622, P. R. China
| | - Dan Wang
- Chronic Diseases Research Center, Dalian University College of Medicine, Dalian, Liaoning 116622, P. R. China
| | - Cheng-Hao Zhang
- Department of Oral Teaching and Research, Yanbian University College of Medicine, Yanji, Jilin Province 133002, P. R. China
| | - Shuo Yuan
- Chronic Diseases Research Center, Dalian University College of Medicine, Dalian, Liaoning 116622, P. R. China
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, P. R. China
| | - Qing-Gao Zhang
- Chronic Diseases Research Center, Dalian University College of Medicine, Dalian, Liaoning 116622, P. R. China
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Zhang Q, Liu S, Wu J, Zhu S, Wu Y, Wu S, Zhang S. Non-alcoholic fatty liver degree and long-term risk of incident inflammatory bowel disease: A large-scale prospective cohort study. Chin Med J (Engl) 2024; 137:1705-1714. [PMID: 37962217 PMCID: PMC11268827 DOI: 10.1097/cm9.0000000000002859] [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: 04/17/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD) have shown similar worsening epidemic patterns globally and shared various overlapping pathophysiological mechanisms. However, evidence on the relationship between NAFLD and IBD risk is lacking. We aimed to investigate the associations between long-term risk of incident IBD and NAFLD in a large prospective cohort. METHODS Participants from the United Kingdom Biobank cohort ( https://biobank.ndph.ox.ac.uk/ ) who were free of IBD and alcoholic liver disease at baseline were enrolled. Baseline non-alcoholic fatty liver degree was measured by the well-established fatty liver index (FLI). The outcomes of interest included incident IBD, ulcerative colitis (UC), and Crohn's disease (CD). Multivariable Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS Among 418,721 participants (mean FLI: 48.11 ± 30.11), 160,807 (38.40%) participants were diagnosed as NAFLD at baseline. During a median of 12.4 years' follow-up, 2346 incident IBD cases (1545 UC, 653 CD, and 148 IBD-unclassified) were identified. Due to limited events, those IBD-unclassified were combined in UC or CD when examining the associated risk of UC or CD, separately. Compared with the lowest quartile of FLI, the highest quartile showed a separately 36.00%, 25.00%, and 58.00% higher risk of incident IBD (HR Q4 vs.Q1 = 1.36, 95% CI: 1.19-1.55, Ptrend <0.001), UC (HR Q4 vs.Q1 = 1.25, 95% CI: 1.07-1.46, Ptrend = 0.047), and CD (HR Q4 vs.Q1 = 1.58, 95% CI: 1.26-1.97, Ptrend <0.001) after multivariable adjustment. Compared with non-NAFLD, NAFLD participants had a significantly higher risk of incident IBD (HR = 1.13, 95% CI: 1.04-1.24) and CD (HR = 1.36, 95% CI: 1.17-1.58). CONCLUSIONS Higher degree of non-alcoholic fatty liver is associated with increased risk of incident IBD. Interventions aimed at improving NAFLD may be a potential targeted strategy for the detection and treatment of IBD.
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Affiliation(s)
| | | | | | | | | | - Shanshan Wu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, China
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Diez-Martin E, Hernandez-Suarez L, Muñoz-Villafranca C, Martin-Souto L, Astigarraga E, Ramirez-Garcia A, Barreda-Gómez G. Inflammatory Bowel Disease: A Comprehensive Analysis of Molecular Bases, Predictive Biomarkers, Diagnostic Methods, and Therapeutic Options. Int J Mol Sci 2024; 25:7062. [PMID: 39000169 PMCID: PMC11241012 DOI: 10.3390/ijms25137062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 06/15/2024] [Accepted: 06/25/2024] [Indexed: 07/16/2024] Open
Abstract
In inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), the immune system relentlessly attacks intestinal cells, causing recurrent tissue damage over the lifetime of patients. The etiology of IBD is complex and multifactorial, involving environmental, microbiota, genetic, and immunological factors that alter the molecular basis of the organism. Among these, the microbiota and immune cells play pivotal roles; the microbiota generates antigens recognized by immune cells and antibodies, while autoantibodies target and attack the intestinal membrane, exacerbating inflammation and tissue damage. Given the altered molecular framework, the analysis of multiple molecular biomarkers in patients proves exceedingly valuable for diagnosing and prognosing IBD, including markers like C reactive protein and fecal calprotectin. Upon detection and classification of patients, specific treatments are administered, ranging from conventional drugs to new biological therapies, such as antibodies to neutralize inflammatory molecules like tumor necrosis factor (TNF) and integrin. This review delves into the molecular basis and targets, biomarkers, treatment options, monitoring techniques, and, ultimately, current challenges in IBD management.
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Affiliation(s)
- Eguzkiñe Diez-Martin
- Research and Development Department, IMG Pharma Biotech S.L., 48170 Zamudio, Spain
- Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
| | - Leidi Hernandez-Suarez
- Research and Development Department, IMG Pharma Biotech S.L., 48170 Zamudio, Spain
- Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
| | - Carmen Muñoz-Villafranca
- Department of Gastroenterology, University Hospital of Basurto, Avda Montevideo 18, 48013 Bilbao, Spain
| | - Leire Martin-Souto
- Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
| | - Egoitz Astigarraga
- Research and Development Department, IMG Pharma Biotech S.L., 48170 Zamudio, Spain
| | - Andoni Ramirez-Garcia
- Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
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Han A, Yang M, Chen B, Cao G, Xu J, Meng T, Liu Y, Wang Z, Zhou Y, Xu N, Han W, Sun H, Mei Q, Zhu L, Xiong M. Microbiome and its relevance to indigenous inflammatory bowel diseases in China. Gene 2024; 909:148257. [PMID: 38367851 DOI: 10.1016/j.gene.2024.148257] [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: 11/24/2023] [Revised: 01/26/2024] [Accepted: 02/05/2024] [Indexed: 02/19/2024]
Abstract
BACKGROUND Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract with an unknown etiology. Although dysbiosis is implicated in its pathogenesis, deep sequencing and oral microbiota study in Chinese IBD patients is absent. AIM To explore the role of oral / intestinal microbiota in patients with IBD and the potential associations therein. METHODS Clinical data, fecal and saliva samples were harvested from 80 patients with IBD (Crohn's disease, CD, n = 69; Ulcerative colitis, UC, n = 11) and 24 normal controls. Microbiomics (16S rRNA sequencing and 16S rRNA full-length sequencing) were used to detect and analyze the difference between IBD patients and normal control. RESULTS Compared with normal controls, a higher abundance of the intestinal Shigella spp. (Shigella flexneri and Shigella sonnei, which were positively relate to the severity of IBD), lower abundance of intestinal probiotics (Prevotella, Faecalibacterium and Roseburia), and higher abundance of oral Neisseria were present in IBD patients with microbiome. The higher inflammation-related markers, impaired hepatic and renal function, and dyslipidaemia were present in patients with IBD. A higher intake of red meat and increased abundance of Clostridium in the gut were found in CD patients, while the elevated abundance of Ruminococcus in the gut was showed in UC ones. The bacterial composition of saliva and fecal samples was completely different, yet there was some correlation in the distribution of dominant probiotics. CONCLUSION Enteric dysbacteriosis and the infections of pathogenic bacteria (Shigella) may associate with the occurrence or development of IBD.
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Affiliation(s)
- Anqi Han
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China
| | - Mingya Yang
- Department of Haematology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China
| | - Bo Chen
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China
| | - Guodong Cao
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China
| | - Junrui Xu
- Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China
| | - Tao Meng
- Department of General Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China
| | - Yu Liu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China
| | - Zhenzhen Wang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China
| | - Yangliu Zhou
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China
| | - Na Xu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China
| | - Wei Han
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China
| | - Haiyi Sun
- Clinical Medical Collage, Anhui Medical University, Hefei 230020, PR China
| | - Qiao Mei
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China.
| | - Lixin Zhu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China.
| | - Maoming Xiong
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China.
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de Síbia CDF, Quaglio AEV, de Oliveira ECS, Pereira JN, Ariede JR, Lapa RML, Severino FE, Reis PP, Sassaki LY, Saad-Hossne R. microRNA-mRNA Networks Linked to Inflammation and Immune System Regulation in Inflammatory Bowel Disease. Biomedicines 2024; 12:422. [PMID: 38398024 PMCID: PMC10886709 DOI: 10.3390/biomedicines12020422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/29/2023] [Accepted: 12/02/2023] [Indexed: 02/25/2024] Open
Abstract
UNLABELLED The molecular processes linked to the development and progression of Crohn's disease (CD) and ulcerative colitis (UC) are not completely understood. MicroRNAs (miRNAs) regulate gene expression and are indicated as diagnostic, prognostic, and predictive biomarkers in chronic degenerative diseases. Our objectives included the identification of global miRNA expression in CD and UC, as well as miRNA target genes, miRNA-mRNA interaction networks, and biological functions associated with these different forms of inflammatory bowel disease (IBD). METHODS By performing a comprehensive meta-analysis, we integrated miRNA expression data from nine studies in IBD. We obtained detailed information on significantly deregulated miRNAs (fold change, FC ≥ 2 and p < 0.05), sample type and number, and platform applied for analysis in the training and validation sets. Further bioinformatic analyses were performed to identify miRNA target genes, by using the microRNA Data Integration Portal tool. We also sought to identify statistically enriched pathways of genes regulated by miRNAs using ToppGene Suite. Additional analyses were performed to filter for genes expressed in intestinal tissue using the European Bioinformatics Institute (EBI) database. RESULTS Our findings showed the upregulation of 15 miRNAs in CD and 33 in UC. Conversely, six miRNAs were downregulated in CD, while seven were downregulated in UC. These results indicate a greater deregulation of miRNAs in UC compared to CD. Of note, miRNA target genes were enriched for immune system regulation pathways. Among significantly deregulated miRNAs with a higher number of miRNA-target gene interactions, we identified miR-199a-5p and miR-362-3p altered in CD, while among UC case patients, miRNA-target gene interactions were higher for miR-155-5p. CONCLUSIONS The identified miRNAs play roles in regulating genes associated with immune system regulation and inflammation in IBD. Such miRNAs and their target genes have the potential to serve as clinically relevant biomarkers. These findings hold promise for enhancing the accuracy of diagnoses and facilitating the development of personalized treatment strategies for individuals with various forms of IBD.
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Affiliation(s)
- Carina de F. de Síbia
- Department of Surgery and Orthopedics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (C.d.F.d.S.); (J.R.A.); (F.E.S.); (P.P.R.)
| | - Ana E. V. Quaglio
- Laboratory of Phytomedicines, Pharmacology and Biotechnology (PhytoPharmaTec), Department of Biophysics and Pharmacology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18607-440, SP, Brazil;
| | - Ellen C. S. de Oliveira
- Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (J.N.P.); (L.Y.S.)
| | - Jéssica N. Pereira
- Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (J.N.P.); (L.Y.S.)
| | - Jovita R. Ariede
- Department of Surgery and Orthopedics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (C.d.F.d.S.); (J.R.A.); (F.E.S.); (P.P.R.)
- Experimental Research Unity (UNIPEX), Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil
| | - Rainer M. L. Lapa
- Facultad de Ingeniería Zootecnista, Agronegocios y Biotecnología, Instituto de Investigación en Ganadería y Biotecnología, Universidad Nacional Toribio Rodríguez de Mendoza de Amazonas, Chachapoyas 01001, Peru;
- Facultad de Ciencias de la Salud, Instituto de Investigación de Salud Integral Intercultural, Universidad Nacional Toribio Rodríguez de Mendoza de Amazonas, Chachapoyas 01001, Peru
| | - Fábio E. Severino
- Department of Surgery and Orthopedics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (C.d.F.d.S.); (J.R.A.); (F.E.S.); (P.P.R.)
- Experimental Research Unity (UNIPEX), Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil
| | - Patricia P. Reis
- Department of Surgery and Orthopedics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (C.d.F.d.S.); (J.R.A.); (F.E.S.); (P.P.R.)
- Experimental Research Unity (UNIPEX), Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil
| | - Lígia Y. Sassaki
- Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (J.N.P.); (L.Y.S.)
| | - Rogerio Saad-Hossne
- Department of Surgery and Orthopedics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (C.d.F.d.S.); (J.R.A.); (F.E.S.); (P.P.R.)
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11
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Wang HL, Wang ZY, Tian J, Ma DR, Shi CH. Association between inflammatory bowel disease and Parkinson's disease: a prospective cohort study of 468,556 UK biobank participants. Front Aging Neurosci 2024; 15:1294879. [PMID: 38288279 PMCID: PMC10822879 DOI: 10.3389/fnagi.2023.1294879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 12/31/2023] [Indexed: 01/31/2024] Open
Abstract
Introduction Inflammatory Bowel Disease (IBD) and Parkinson's disease (PD) are both chronic, progressive disorders. As such, given the inconclusive results of extensive research on the association between IBD and PD, our study intends to examine this relationship further using the UK Biobank database. Methods We conducted a prospective cohort study using the Cox proportional hazards model, analyzing data from the UK Biobank to investigate the relationship between IBD and PD, following subjects until PD diagnosis, loss to follow up, death or study termination on 30 June, 2023. Results The results show that IBD had no effect on the risk of PD (HR: 1.356, 95% CI: 0.941-1.955, p = 0.103), and the effect remained consistent in specific Crohn's disease, ulcerative colitis or unclassified IBD populations. In addition, after sensitivity analysis using propensity matching scores and excluding patients diagnosed with PD 5 or 10 years after baseline, IBD had no effect on the risk of PD. However, in the subgroup analysis, we found that in females (HR: 1.989, 95% CI: 1.032-3.835, p = 0.040), the polygenic risk score was highest (HR: 2.476, 95% CI: 1.401-4.374, p = 0.002), and having ulcerative colitis without hypertension (HR: 2.042, 95% CI: 1.128-3.697, p = 0.018) was associated with an increased risk of PD. Conclusion In conclusion, over an average follow-up period of 13.93 years, we found no significant association between IBD and PD.
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Affiliation(s)
- Hai-li Wang
- Department of Surgery ICU, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China
| | - Zhi-yun Wang
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China
| | - Jie Tian
- Zhengzhou Railway Vocational and Technical College, Zhengzhou, Henan, China
| | - Dong-rui Ma
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China
| | - Chang-he Shi
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China
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12
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Migliorisi G, Vella G, Dal Buono A, Gabbiadini R, Busacca A, Loy L, Bezzio C, Vinciguerra P, Armuzzi A. Ophthalmological Manifestations in Inflammatory Bowel Diseases: Keep an Eye on It. Cells 2024; 13:142. [PMID: 38247834 PMCID: PMC10814681 DOI: 10.3390/cells13020142] [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: 12/15/2023] [Revised: 12/31/2023] [Accepted: 01/09/2024] [Indexed: 01/23/2024] Open
Abstract
BACKGROUND AND AIMS Inflammatory bowel diseases (IBD) are multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. However, a broad spectrum of extraintestinal manifestations (EIMs) is associated with IBD, affecting several organs and systems, such as the skin, musculoskeletal and hepatobiliary systems, and, not least, the eye. Approximately 10% of IBD patients can develop ocular EIMs (O-EIMs) with a higher prevalence in Crohn's disease (CD). Eye-redness, photophobia, pain, and blurred vision are the common symptoms, with a wide rate of severity and clinical impact on the quality of life. This narrative review aims to summarize the prevalence, pathogenesis, and current evidence-based management of O-EIMs, underlying the importance of a holistic approach and specialties collaboration for a prompt diagnosis and treatment. METHODS PubMed was searched up to December 2023 to identify relevant studies investigating the pathogenesis, epidemiology, and treatment of O-EIMs in IBD patients. RESULTS The mechanisms underlying O-EIMs are partially unknown, encompassing immune dysregulation, shared antigens between the eye and the gut, genetic predisposition, and systemic inflammation driven by high levels of interleukins and cytokines in IBD patients. The complexity of O-EIMs' pathogenesis reflects in the management of these conditions, varying from topical and systemic steroids to immunomodulatory molecules and biologic therapy, such as anti-tumor necrosis factor (TNF)-alpha. A multidisciplinary approach is the backbone of the management of O-EIMs.
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Affiliation(s)
- Giulia Migliorisi
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (G.M.); (A.D.B.); (R.G.); (A.B.); (L.L.); (C.B.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy;
| | - Giovanna Vella
- Department of Ophtalmology, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy;
| | - Arianna Dal Buono
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (G.M.); (A.D.B.); (R.G.); (A.B.); (L.L.); (C.B.)
| | - Roberto Gabbiadini
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (G.M.); (A.D.B.); (R.G.); (A.B.); (L.L.); (C.B.)
| | - Anita Busacca
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (G.M.); (A.D.B.); (R.G.); (A.B.); (L.L.); (C.B.)
| | - Laura Loy
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (G.M.); (A.D.B.); (R.G.); (A.B.); (L.L.); (C.B.)
| | - Cristina Bezzio
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (G.M.); (A.D.B.); (R.G.); (A.B.); (L.L.); (C.B.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy;
| | - Paolo Vinciguerra
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy;
- Department of Ophtalmology, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy;
| | - Alessandro Armuzzi
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (G.M.); (A.D.B.); (R.G.); (A.B.); (L.L.); (C.B.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy;
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13
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Vebr M, Pomahačová R, Sýkora J, Schwarz J. A Narrative Review of Cytokine Networks: Pathophysiological and Therapeutic Implications for Inflammatory Bowel Disease Pathogenesis. Biomedicines 2023; 11:3229. [PMID: 38137450 PMCID: PMC10740682 DOI: 10.3390/biomedicines11123229] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 10/11/2023] [Accepted: 11/22/2023] [Indexed: 12/24/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a lifelong inflammatory immune mediated disorder, encompassing Crohn's disease (CD) and ulcerative colitis (UC); however, the cause and specific pathogenesis of IBD is yet incompletely understood. Multiple cytokines produced by different immune cell types results in complex functional networks that constitute a highly regulated messaging network of signaling pathways. Applying biological mechanisms underlying IBD at the single omic level, technologies and genetic engineering enable the quantification of the pattern of released cytokines and new insights into the cytokine landscape of IBD. We focus on the existing literature dealing with the biology of pro- or anti-inflammatory cytokines and interactions that facilitate cell-based modulation of the immune system for IBD inflammation. We summarize the main roles of substantial cytokines in IBD related to homeostatic tissue functions and the remodeling of cytokine networks in IBD, which may be specifically valuable for successful cytokine-targeted therapies via marketed products. Cytokines and their receptors are validated targets for multiple therapeutic areas, we review the current strategies for therapeutic intervention and developing cytokine-targeted therapies. New biologics have shown efficacy in the last few decades for the management of IBD; unfortunately, many patients are nonresponsive or develop therapy resistance over time, creating a need for novel therapeutics. Thus, the treatment options for IBD beyond the immune-modifying anti-TNF agents or combination therapies are expanding rapidly. Further studies are needed to fully understand the immune response, networks of cytokines, and the direct pathogenetic relevance regarding individually tailored, safe and efficient targeted-biotherapeutics.
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Affiliation(s)
- Marek Vebr
- Departments of Pediatrics, Faculty Hospital, Faculty of Medicine in Pilsen, Charles University of Prague, 323 00 Pilsen, Czech Republic; (R.P.); (J.S.); (J.S.)
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14
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Tang YZ, Liu Y, Chen YP, Feng TT, Liu YY, Wang Y, Zhang JP, Xu WH. Citropten alleviates acute and recurrent colitis via blockage of NF-κB and JAK/STAT3 pathways. Int Immunopharmacol 2023; 125:111102. [PMID: 37922567 DOI: 10.1016/j.intimp.2023.111102] [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: 08/16/2023] [Revised: 10/10/2023] [Accepted: 10/18/2023] [Indexed: 11/07/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory bowel disease, which is characterized by inflammation, with many symptoms including diarrhea, abdominal pain, bloody stool, and weight loss. It is difficult to completely cure and promising therapeutic drug candidates are urgently needed. Citropten, a coumarin-like compound found in traditional Chinese medicine such as Finger Citron Fruit, notopterygium root and citrus peel, has been shown to inhibit the proliferation of tumor cells, protect against depression and suppress the production of inflammatory mediators. In this study, we demonstrated that citropten could alleviate dextran sulfate sodium (DSS)-induced acute and recurrent colitis in mice, with significant improvement in body weight loss, disease activity index, shortened colon length and histological changes. Moreover, citropten dramatically decreased the production of pro-inflammatory mediators in colon tissues and effectively suppressed the proportion of Th17 cells in spleen. Mechanism investigations revealed that citropten significantly inhibited the activation of NF-κB and JAK/STAT3 signaling pathways, thus leading to decreased inflammation, Th17 cells and alleviative colitis. These findings provide novel insights into the anti-colitis effect of citropten, which may be a promising drug candidate for treatment of IBD.
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Affiliation(s)
- Yu Zhen Tang
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China
| | - Ying Liu
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, PR China
| | - Ya Ping Chen
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China
| | - Ting Ting Feng
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China
| | - Ya Yi Liu
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China
| | - Yan Wang
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China; School of Pharmacy, Second Military Medical University, Shanghai 200433, PR China
| | - Jun Ping Zhang
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China; School of Pharmacy, Second Military Medical University, Shanghai 200433, PR China.
| | - Wei Heng Xu
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China; School of Pharmacy, Second Military Medical University, Shanghai 200433, PR China.
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15
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Eiberg H, Olsson JB, Bak M, Bang-Berthelsen CH, Troelsen JT, Hansen L. A family with ulcerative colitis maps to 7p21.1 and comprises a region with regulatory activity for the aryl hydrocarbon receptor gene. Eur J Hum Genet 2023; 31:1440-1446. [PMID: 36732664 PMCID: PMC10689720 DOI: 10.1038/s41431-023-01298-9] [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: 08/16/2022] [Revised: 11/16/2022] [Accepted: 01/18/2023] [Indexed: 02/04/2023] Open
Abstract
We have mapped a locus on chromosome 7p22.3-7p15.3 spanning a 22.4 Mb region for ulcerative colitis (UC) by whole genome linkage analyses of a large Danish family. The family represent three generations with UC segregating as an autosomal dominant trait with variable expressivity. The whole-genome scan resulted in a logarithm of odds score (LOD score) of Z = 3.31, and a whole genome sequencing (WGS) of two affected excluded disease-causing mutations in the protein coding genes. Two rare heterozygote variants, rs182281985:G>A and rs541426369:G>A, both with low allele frequencies (MAF A:0.0001, gnomAD ver3.1.2), were found in clusters of ChiP-seq transcription factors binding sites close to the AHR (aryl hydrocarbon receptor) gene and the UC associated SNP rs1077773:G>A. Testing the two SNPs in a promoter reporter assay for regulatory activity revealed that rs182281985:G>A influenced the AHR promoter. These results suggest a regulatory region that include rs182281985:G>A close to the UC GWAS SNP rs1077773:G>A and further demonstrate evidence that the AHR gene on the 7p-tel region is a candidate susceptible gene for UC.
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Affiliation(s)
- Hans Eiberg
- RCLINK, Department of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark.
| | - Josephine B Olsson
- Department of Science and Environment, Roskilde University, Roskilde, Denmark
- Department of Clinical Immunology, Zealand University Hospital, Naestved, Denmark
| | - Mads Bak
- Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Claus Heiner Bang-Berthelsen
- Research Group for Microbial Biotechnology and Biorefining, National Food Institute, Technical University of Denmark, Kemitorvet building 202, 2800 Kgs, Lyngby, Denmark
| | - Jesper T Troelsen
- Department of Science and Environment, Roskilde University, Roskilde, Denmark
| | - Lars Hansen
- Department of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark
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16
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Minjoz S, Sinniger V, Hot P, Bonaz B, Pellissier S. The burden of early life stress in chronic inflammatory bowel diseases. J Health Psychol 2023; 28:1204-1216. [PMID: 37203800 DOI: 10.1177/13591053231173918] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/20/2023] Open
Abstract
The aim of this study was to evaluate the prevalence of early life stress (ELS) in a population with inflammatory bowel diseases (IBD) and to estimate its burden on mental, physical, and digestive health. Ninety-three participants with IBD were asked to anonymously complete questionnaires (Childhood Trauma Questionnaire-Short Form, Early Life Event Scale, Perceived Stress Scale, Hospital Anxiety and Depression Scale, Ways of Coping Checklist, Gastro-Intestinal Quality of Life Index questionnaire, and ad hoc questions about symptoms). The prevalence of patients with IBD who were exposed to at least one childhood abuse was 53%. Mental health and quality of life were significantly poorer in patients with IBD who were exposed to early abuse than in those who were not. Patients exposed to ELS had also more digestive perturbations and fatigue. These results suggest that early abuse should be considered a component of IBD care.
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Affiliation(s)
- Séphora Minjoz
- Université Savoie Mont Blanc, Université Grenoble Alpes, LIP/PC2S, France
- Université Savoie Mont Blanc, Université Grenoble Alpes, LPNC, France
| | - Valérie Sinniger
- Université Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, France
| | - Pascal Hot
- Université Savoie Mont Blanc, Université Grenoble Alpes, LPNC, France
- Institut Universitaire de France, France
| | - Bruno Bonaz
- Université Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, France
| | - Sonia Pellissier
- Université Savoie Mont Blanc, Université Grenoble Alpes, LIP/PC2S, France
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17
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Dvornikova KA, Platonova ON, Bystrova EY. Inflammatory Bowel Disease: Crosstalk between Histamine, Immunity, and Disease. Int J Mol Sci 2023; 24:9937. [PMID: 37373085 DOI: 10.3390/ijms24129937] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 05/30/2023] [Accepted: 06/07/2023] [Indexed: 06/29/2023] Open
Abstract
Inflammatory bowel disease (IBD) is increasingly recognized as a serious, worldwide public health concern. It is generally acknowledged that a variety of factors play a role in the pathogenesis of this group of chronic inflammatory diseases. The diversity of molecular actors involved in IBD does not allow us to fully assess the causal relationships existing in such interactions. Given the high immunomodulatory activity of histamine and the complex immune-mediated nature of inflammatory bowel disease, the role of histamine and its receptors in the gut may be significant. This paper has been prepared to provide a schematic of the most important and possible molecular signaling pathways related to histamine and its receptors and to assess their relevance for the development of therapeutic approaches.
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Affiliation(s)
| | - Olga N Platonova
- I.P. Pavlov Institute of Physiology RAS, St. Petersburg 199034, Russia
| | - Elena Y Bystrova
- I.P. Pavlov Institute of Physiology RAS, St. Petersburg 199034, Russia
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18
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Sun M, Ju J, Xu H, Wang Y. Intestinal fungi and antifungal secretory immunoglobulin A in Crohn's disease. Front Immunol 2023; 14:1177504. [PMID: 37359518 PMCID: PMC10285161 DOI: 10.3389/fimmu.2023.1177504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 05/30/2023] [Indexed: 06/28/2023] Open
Abstract
The human gastrointestinal tract harbors trillions of commensal microorganisms. Emerging evidence points to a possible link between intestinal fungal dysbiosis and antifungal mucosal immunity in inflammatory bowel disease, especially in Crohn's disease (CD). As a protective factor for the gut mucosa, secretory immunoglobulin A (SIgA) prevents bacteria from invading the intestinal epithelium and maintains a healthy microbiota community. In recent years, the roles of antifungal SIgA antibodies in mucosal immunity, including the regulation of intestinal immunity binding to hyphae-associated virulence factors, are becoming increasingly recognized. Here we review the current knowledge on intestinal fungal dysbiosis and antifungal mucosal immunity in healthy individuals and in patients with CD, discuss the factors governing antifungal SIgA responses in the intestinal mucosa in the latter group, and highlight potential antifungal vaccines targeting SIgA to prevent CD.
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19
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Zhu Y, Wang Y, Xia G, Zhang X, Deng S, Zhao X, Xu Y, Chang G, Tao Y, Li M, Li H, Huang X, Chan HF. Oral Delivery of Bioactive Glass-Loaded Core-Shell Hydrogel Microspheres for Effective Treatment of Inflammatory Bowel Disease. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2207418. [PMID: 37092589 PMCID: PMC10288274 DOI: 10.1002/advs.202207418] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 03/13/2023] [Indexed: 05/03/2023]
Abstract
Resolving inflammation and promoting intestinal tissue regeneration are critical for inflammatory bowel disease (IBD) treatment. Bioactive glass (BG) is a clinically approved bone graft material and has been shown to modulate inflammatory response, but it is unknown whether BG can be applied to treat IBD. Here, it is reported that BG attenuates pro-inflammatory response of lipopolysaccharide (LPS)-stimulated macrophages and hence reduces inflammatory damage to intestinal organoids in vitro. In addition, zein/sodium alginate-based core-shell microspheres (Zein/SA/BG) are developed for oral delivery of BG, which helps prevent premature dissolution of BG in the stomach. The results show that Zein/SA/BG protects BG from a gastric-simulated environment while dissolved in an intestinal-simulated environment. When administered to acute and chronic colitis mice model, Zein/SA/BG significantly reduces intestinal inflammation, promotes epithelial tissue regeneration, and partially restores microbiota homeostasis. These findings are the first to reveal the therapeutic efficacy of BG against IBD, which may provide a new therapeutic approach at low cost for effective IBD treatment.
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Affiliation(s)
- Yanlun Zhu
- Key Laboratory for Regenerative Medicine of the Ministry of Education of ChinaSchool of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongShatinHong Kong SAR999077China
- Institute for Tissue Engineering and Regenerative MedicineThe Chinese University of Hong KongShatinHong Kong SAR999077China
| | - Yiwei Wang
- Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine600 Yishan RdShanghai200233China
| | - Guanggai Xia
- Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine600 Yishan RdShanghai200233China
| | - Xuerao Zhang
- Key Laboratory for Regenerative Medicine of the Ministry of Education of ChinaSchool of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongShatinHong Kong SAR999077China
- Institute for Tissue Engineering and Regenerative MedicineThe Chinese University of Hong KongShatinHong Kong SAR999077China
| | - Shuai Deng
- Key Laboratory for Regenerative Medicine of the Ministry of Education of ChinaSchool of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongShatinHong Kong SAR999077China
- Institute for Tissue Engineering and Regenerative MedicineThe Chinese University of Hong KongShatinHong Kong SAR999077China
- Cell Therapy and Cell Drugs of Luzhou Key LaboratorySchool of PharmacySouthwest Medical UniversityLuzhouSichuan646000China
| | - Xiaoyu Zhao
- Key Laboratory for Regenerative Medicine of the Ministry of Education of ChinaSchool of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongShatinHong Kong SAR999077China
- Institute for Tissue Engineering and Regenerative MedicineThe Chinese University of Hong KongShatinHong Kong SAR999077China
| | - Yanteng Xu
- Laboratory of Biomaterials and Translational MedicineCenter for NanomedicineThe Third Affiliated HospitalSun Yat‐sen UniversityGuangzhou510630China
| | - Guozhu Chang
- Key Laboratory for Regenerative Medicine of the Ministry of Education of ChinaSchool of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongShatinHong Kong SAR999077China
- Institute for Tissue Engineering and Regenerative MedicineThe Chinese University of Hong KongShatinHong Kong SAR999077China
| | - Yu Tao
- Laboratory of Biomaterials and Translational MedicineCenter for NanomedicineThe Third Affiliated HospitalSun Yat‐sen UniversityGuangzhou510630China
| | - Mingqiang Li
- Laboratory of Biomaterials and Translational MedicineCenter for NanomedicineThe Third Affiliated HospitalSun Yat‐sen UniversityGuangzhou510630China
- Guangdong Provincial Key Laboratory of Liver DiseaseGuangzhou510630China
| | - Haiyan Li
- Chemical and Environmental EngineeringSchool of EngineeringRMIT University124 La Trobe StMelbourneVIC3000Australia
| | - Xinyu Huang
- Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine600 Yishan RdShanghai200233China
| | - Hon Fai Chan
- Key Laboratory for Regenerative Medicine of the Ministry of Education of ChinaSchool of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongShatinHong Kong SAR999077China
- Institute for Tissue Engineering and Regenerative MedicineThe Chinese University of Hong KongShatinHong Kong SAR999077China
- Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics999077Hong Kong SARChina
- Center for Neuromusculoskeletal Restorative MedicineHong Kong Science ParkHong Kong SAR999077China
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20
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BASOGLU IA, KARAKOYUN B. Crohn’s disease: Etiology, pathogenesis and treatment strategies. MARMARA MEDICAL JOURNAL 2023; 36:249-254. [DOI: 10.5472/marumj.1307982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Crohn’s disease (CD), which can be localized in any part of the gastrointestinal tract, is a disease characterized by an irregular immune
response to normal and/or abnormal microbial antigens. Recent studies show many extensive data about the roles of genetic and
environmental factors, immune function, and gut microbiota in CD. Although, less invasive biomarkers are currently being developed,
the diagnosis of the disease is still based on the endoscopy and histological evaluation of biopsy samples. The most common symptoms
are diarrhea, abdominal pain, weight loss, and fatigue. Despite the improvements in the treatment methods in the last decade, there
is no definitive treatment since the etiology of CD is not known exactly. Therapeutic strategies focus on reducing inflammation and
symptoms, maintaining clinical remission, and improving quality of life.
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21
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Tian CM, Yang MF, Xu HM, Zhu MZ, Zhang Y, Yao J, Wang LS, Liang YJ, Li DF. Mesenchymal Stem Cell-derived Exosomes: Novel Therapeutic Approach for Inflammatory Bowel Diseases. Stem Cells Int 2023; 2023:4245704. [PMID: 37056457 PMCID: PMC10089786 DOI: 10.1155/2023/4245704] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 02/19/2023] [Accepted: 03/22/2023] [Indexed: 04/07/2023] Open
Abstract
As double membrane-encapsulated nanovesicles (30-150 nm), exosomes (Exos) shuttle between different cells to mediate intercellular communication and transport active cargoes of paracrine factors. The anti-inflammatory and immunomodulatory activities of mesenchymal stem cell (MSC)-derived Exos (MSC-Exos) provide a rationale for novel cell-free therapies for inflammatory bowel disease (IBD). Growing evidence has shown that MSC-Exos can be a potential candidate for treating IBD. In the present review, we summarized the most critical advances in the properties of MSC-Exos, provided the research progress of MSC-Exos in treating IBD, and discussed the molecular mechanisms underlying these effects. Collectively, MSC-Exos had great potential for cell-free therapy in IBD. However, further studies are required to understand the full dimensions of the complex Exo system and how to optimize its effects.
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Affiliation(s)
- Cheng-mei Tian
- Department of Gastroenterology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China
- Department of Emergency, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020 Guangdong, China
| | - Mei-feng Yang
- Department of Hematology, Yantian District People's Hospital, Shenzhen, Guangdong, China
| | - Hao-ming Xu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Min-zheng Zhu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Yuan Zhang
- Department of Medical Administration, Huizhou Institute of Occupational Diseases Control and Prevention, Huizhou, Guangdong, China
| | - Jun Yao
- Department of Gastroenterology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China
| | - Li-sheng Wang
- Department of Gastroenterology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China
| | - Yu-jie Liang
- Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen, Guangdong, China
| | - De-feng Li
- Department of Gastroenterology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China
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22
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Liang J, Li X, Lei W, Tan P, Han M, Li H, Yue T, Wang Z, Gao Z. Serum metabolomics combined with 16S rRNA sequencing to reveal the effects of Lycium barbarum polysaccharide on host metabolism and gut microbiota. Food Res Int 2023; 165:112563. [PMID: 36869545 DOI: 10.1016/j.foodres.2023.112563] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 01/18/2023] [Accepted: 01/29/2023] [Indexed: 02/05/2023]
Abstract
Gut microbes and microbial metabolites derived from polysaccharides mediate beneficial effects related to polysaccharides consumption. Lycium barbarum polysaccharide (LBP) is the main bioactive components in L. barbarum fruits and possesses considerable health-promoting effects. In the present study, we aimed to investigate whether LBP supplementation influenced host metabolic responses and gut microbiota in healthy mice, and to identify bacterial taxa associated with the observed beneficial effects. Our results indicated that mice supplied with LBP at 200 mg/kg BW showed lower serum total cholesterol (TC), triglyceride (TG), and liver TG levels. LBP supplementation strengthened the antioxidant capacity of liver, supported the growth of Lactobacillus and Lactococcus, and stimulated short-chain fatty acids (SCFAs) production. Serum metabolomic analysis revealed that fatty acid degradation pathways were enriched, and RT-PCR further confirmed that LBP up-regulated the expression of liver genes involved in fatty acid oxidation. The Spearman's correlation analysis indicated that some serum and liver lipid profiles and hepatic SOD activity were associated with Lactobacillus, Lactococcus, Ruminococcus, Allobaculum and AF12. Collectively, these findings provide new evidence for the potential preventive effect of LBP consumption on hyperlipidemia and nonalcoholic fatty liver disease.
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Affiliation(s)
- Jingjing Liang
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China
| | - Xiaohan Li
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China
| | - Wenzhi Lei
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China
| | - Pei Tan
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China
| | - Mengzhen Han
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China
| | - Hongcai Li
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China
| | - Tianli Yue
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China
| | - Zhouli Wang
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China
| | - Zhenpeng Gao
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China.
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23
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Laurindo LF, de Maio MC, Minniti G, de Góes Corrêa N, Barbalho SM, Quesada K, Guiguer EL, Sloan KP, Detregiachi CRP, Araújo AC, de Alvares Goulart R. Effects of Medicinal Plants and Phytochemicals in Nrf2 Pathways during Inflammatory Bowel Diseases and Related Colorectal Cancer: A Comprehensive Review. Metabolites 2023; 13:243. [PMID: 36837862 PMCID: PMC9966918 DOI: 10.3390/metabo13020243] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 02/02/2023] [Accepted: 02/06/2023] [Indexed: 02/10/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are related to nuclear factor erythroid 2-related factor 2 (Nrf2) dysregulation. In vitro and in vivo studies using phytocompounds as modulators of the Nrf2 signaling in IBD have already been published. However, no existing review emphasizes the whole scenario for the potential of plants and phytocompounds as regulators of Nrf2 in IBD models and colitis-associated colorectal carcinogenesis. For these reasons, this study aimed to build a review that could fill this void. The PubMed, EMBASE, COCHRANE, and Google Scholar databases were searched. The literature review showed that medicinal plants and phytochemicals regulated the Nrf2 on IBD and IBD-associated colorectal cancer by amplifying the expression of the Nrf2-mediated phase II detoxifying enzymes and diminishing NF-κB-related inflammation. These effects improve the bowel environment, mucosal barrier, colon, and crypt disruption, reduce ulceration and microbial translocation, and consequently, reduce the disease activity index (DAI). Moreover, the modulation of Nrf2 can regulate various genes involved in cellular redox, protein degradation, DNA repair, xenobiotic metabolism, and apoptosis, contributing to the prevention of colorectal cancer.
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Affiliation(s)
- Lucas Fornari Laurindo
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, São Paulo, Brazil
- Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Marília (FAMEMA), Avenida Monte Carmelo, 800, Marília 17519-030, São Paulo, Brazil
| | - Mariana Canevari de Maio
- Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Marília (FAMEMA), Avenida Monte Carmelo, 800, Marília 17519-030, São Paulo, Brazil
| | - Giulia Minniti
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, São Paulo, Brazil
| | - Natália de Góes Corrêa
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, São Paulo, Brazil
| | - Sandra Maria Barbalho
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, São Paulo, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, São Paulo, Brazil
- Department of Biochemistry and Nutrition, School of Food and Technology of Marília (FATEC), Avenida Castro Alves, 62, Marília 17500-000, São Paulo, Brazil
| | - Karina Quesada
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, São Paulo, Brazil
- Department of Biochemistry and Nutrition, School of Food and Technology of Marília (FATEC), Avenida Castro Alves, 62, Marília 17500-000, São Paulo, Brazil
| | - Elen Landgraf Guiguer
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, São Paulo, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, São Paulo, Brazil
- Department of Biochemistry and Nutrition, School of Food and Technology of Marília (FATEC), Avenida Castro Alves, 62, Marília 17500-000, São Paulo, Brazil
| | | | - Claudia R. P. Detregiachi
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, São Paulo, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, São Paulo, Brazil
| | - Adriano Cressoni Araújo
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, São Paulo, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, São Paulo, Brazil
| | - Ricardo de Alvares Goulart
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, São Paulo, Brazil
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24
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HIURA K, MARUYAMA T, WATANABE M, NAKANO K, OKAMURA T, SASAKI H, SASAKI N. Mitotic spindle positioning protein (MISP) deficiency exacerbates dextran sulfate sodium (DSS)-induced colitis in mice. J Vet Med Sci 2023; 85:167-174. [PMID: 36596561 PMCID: PMC10017287 DOI: 10.1292/jvms.22-0483] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 12/07/2022] [Indexed: 12/31/2022] Open
Abstract
Inflammatory bowel disease (IBD) is classified into two types: Crohn's disease and ulcerative colitis. In IBD, the imbalance between the pro-inflammatory and anti-inflammatory cytokines prevents recovery from the inflammatory state, resulting in chronic inflammation in the colon. The mitotic spindle positioning protein (MISP) is localized to the apical membrane in the colon. In this study, we observed increased expression of MISP in the intestinal epithelial cells in dextran sulfate sodium (DSS)-induced colitis in mice. MISP-deficient mice receiving DSS showed significant exacerbation of colitis (e.g., weight loss, loss of the crypts). The intestinal epithelial cells of the MISP-deficient mice showed a trend towards decreased cell proliferation after DSS treatment. Reverse transcription followed by quantitative polymerase chain reaction revealed that the expression levels of Tgfb1, an anti-inflammatory cytokine, were significantly reduced in the colon of MISP-deficient mice compared with the wild-type mice regardless of DSS treatment. These findings indicate that MISP may play a role in the recovery of the colon after inflammation through its anti-inflammatory and proliferative activities, suggesting that MISP may be a new therapeutic target for IBD.
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Affiliation(s)
- Koki HIURA
- Laboratory of Laboratory Animal Science and Medicine, School
of Veterinary Medicine, Kitasato University, Aomori, Japan
| | - Takumi MARUYAMA
- Laboratory of Laboratory Animal Science and Medicine, School
of Veterinary Medicine, Kitasato University, Aomori, Japan
- Department of Laboratory Animal Medicine, Research
Institute, National Center for Global Health and Medicine, Tokyo, Japan
| | - Masaki WATANABE
- Laboratory of Laboratory Animal Science and Medicine, School
of Veterinary Medicine, Kitasato University, Aomori, Japan
| | - Kenta NAKANO
- Department of Laboratory Animal Medicine, Research
Institute, National Center for Global Health and Medicine, Tokyo, Japan
| | - Tadashi OKAMURA
- Department of Laboratory Animal Medicine, Research
Institute, National Center for Global Health and Medicine, Tokyo, Japan
| | - Hayato SASAKI
- Laboratory of Laboratory Animal Science and Medicine, School
of Veterinary Medicine, Kitasato University, Aomori, Japan
| | - Nobuya SASAKI
- Laboratory of Laboratory Animal Science and Medicine, School
of Veterinary Medicine, Kitasato University, Aomori, Japan
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25
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Kumar A, Rani P. A Quick Visible Spectrophotometry Approach For The Assessment Of Mesalazine In Pharmaceutical Preparations. Pharm Chem J 2023. [DOI: 10.1007/s11094-023-02806-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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26
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Muacevic A, Adler JR, Zambrana-Valenzuela R, Iglesias-Escabi IM, Arciniegas-Medina NJ. Development of Very-Early-Onset Inflammatory Bowel Disease After Multiple Early-Life Antibiotic Exposures: A Case Report and Literature Review. Cureus 2023; 15:e33813. [PMID: 36819429 PMCID: PMC9930002 DOI: 10.7759/cureus.33813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/15/2023] [Indexed: 01/17/2023] Open
Abstract
The use of antibiotics has increased drastically over the last few decades. Many antibiotics can target the commensal microbiota and promote gut dysbiosis. These alterations contribute to disease onset and exacerbation. Although the etiology of inflammatory bowel disease (IBD) is mostly unknown, it involves a complex interaction among host genetics, microbiota, environmental factors, and aberrant immune responses. Studies have shown a relationship between very-early-onset inflammatory bowel disease (VEO-IBD) and microbiota alterations. The case discussed in this report endorses the current clinical evidence for this interaction. This is an anonymous record review with no identifiers involving a 23-month-old female patient who was brought to the emergency department by her parents due to persistent bloody diarrhea. Eight days before the presentation, she had experienced watery diarrhea that progressed to bloody stools. The patient had a history of acute otitis media, acute enteritis, and right-arm cutaneous abscess, for which she had received multiple antibiotic therapies. Strategies to manipulate the microbiome through diet, probiotics, antibiotics, or fecal microbiota transplantation (FMT) may be used therapeutically to modulate disease activity. A high index of clinical suspicion for VEO-IBD should be maintained for patients with a history of multiple, recurrent antibiotic use. We believe this case report will raise awareness about the issue of early anaerobic antibiotic exposure and help prevent its unnecessary use and, consequently, prevent gut microbiota dysbiosis that can lead to VEO-IBD. Also, our literature review will hopefully prompt clinicians to consider alternative therapeutic options for this patient population, such as rebuilding intestinal microbiota composition to improve VEO-IBD activity.
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27
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Wang K, Mao T, Lu X, Wang M, Yun Y, Jia Z, Shi L, Jiang H, Li J, Shi R. A potential therapeutic approach for ulcerative colitis: targeted regulation of macrophage polarization through phytochemicals. Front Immunol 2023; 14:1155077. [PMID: 37197668 PMCID: PMC10183582 DOI: 10.3389/fimmu.2023.1155077] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 03/20/2023] [Indexed: 05/19/2023] Open
Abstract
Ulcerative colitis (UC), a type of inflammatory bowel disease characterized by recurring and incurable symptoms, causes immense suffering and economic burden for patients due to the limited treatment options available. Therefore, it is imperative to develop novel and promising strategies, as well as safe and effective drugs, for the clinical management of UC. Macrophages play a critical role as the initial line of defense in maintaining intestinal immune homeostasis, and their phenotypic transformation significantly influences the progression of UC. Scientific studies have demonstrated that directing macrophage polarization toward the M2 phenotype is an effective strategy for the prevention and treatment of UC. Phytochemicals derived from botanical sources have garnered the interest of the scientific community owing to their distinct bioactivity and nutritional value, which have been shown to confer beneficial protective effects against colonic inflammation. In this review, we explicated the influence of macrophage polarization on the development of UC and collated data on the significant potential of natural substances that can target the macrophage phenotype and elucidate the possible mechanism of action for its treatment. These findings may provide novel directions and references for the clinical management of UC.
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Affiliation(s)
- Ke Wang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Tangyou Mao
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Xinyu Lu
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Muyuan Wang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yifei Yun
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Zeyu Jia
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Lei Shi
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Haoxi Jiang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Junxiang Li
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
- *Correspondence: Junxiang Li, ; Rui Shi,
| | - Rui Shi
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
- *Correspondence: Junxiang Li, ; Rui Shi,
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28
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Pytrus W, Akutko K, Pytrus T, Turno-Kręcicka A. A Review of Ophthalmic Complications in Inflammatory Bowel Diseases. J Clin Med 2022; 11:7457. [PMID: 36556071 PMCID: PMC9781961 DOI: 10.3390/jcm11247457] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 11/27/2022] [Accepted: 12/11/2022] [Indexed: 12/23/2022] Open
Abstract
Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic immune-mediated conditions caused by various polygenic and environmental factors. Clinical manifestations of IBD primarily occur in the gastrointestinal tract, but many patients are affected by extraintestinal complications, including eye diseases. Ocular disorders are the third most common extraintestinal manifestation (EIM), following musculoskeletal and mucocutaneous involvement. Episcleritis, frequently occurring in IBD patients, may be associated with exacerbation of the intestinal disease. Uveitis does not correlate with IBD activity but may be related to the presence of other EIMs, particularly erythema nodosum and peripheral arthritis. Early detection and specific therapy of ocular manifestations of IBD are fundamental to avoiding sight-threatening complications. Therefore, ophthalmic evaluation should be performed in all IBD patients. Systemic corticosteroids or immunosuppressants may be inevitable in severe cases to control ocular inflammation. Persistent and relapsing conditions usually respond well to TNF-α-inhibitors. Interdisciplinary cooperation between gastroenterologists and ophthalmologists is fundamental in initiating the appropriate treatment for patients.
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Affiliation(s)
- Wiktoria Pytrus
- Ophthalmonology Clinical Centre SPEKTRUM, 53-334 Wroclaw, Poland
| | - Katarzyna Akutko
- 2nd Department and Clinic of Paediatrics, Gastroenterology and Nutrition, Wroclaw Medical University, 50-369 Wroclaw, Poland
| | - Tomasz Pytrus
- 2nd Department and Clinic of Paediatrics, Gastroenterology and Nutrition, Wroclaw Medical University, 50-369 Wroclaw, Poland
| | - Anna Turno-Kręcicka
- Clinical Department of Ophthalmology, Wroclaw Medical University, 50-556 Wroclaw, Poland
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29
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González Delgado S, Garza-Veloz I, Trejo-Vazquez F, Martinez-Fierro ML. Interplay between Serotonin, Immune Response, and Intestinal Dysbiosis in Inflammatory Bowel Disease. Int J Mol Sci 2022; 23:ijms232415632. [PMID: 36555276 PMCID: PMC9779345 DOI: 10.3390/ijms232415632] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/05/2022] [Accepted: 12/06/2022] [Indexed: 12/14/2022] Open
Abstract
Inflammatory Bowel Disease (IBD) is a chronic gastrointestinal disorder characterized by periods of activity and remission. IBD includes Crohn's disease (CD) and ulcerative colitis (UC), and even though IBD has not been considered as a heritable disease, there are genetic variants associated with increased risk for the disease. 5-Hydroxytriptamine (5-HT), or serotonin, exerts a wide range of gastrointestinal effects under both normal and pathological conditions. Furthermore, Serotonin Transporter (SERT) coded by Solute Carrier Family 6 Member 4 (SLC6A4) gene (located in the 17q11.1-q12 chromosome), possesses genetic variants, such as Serotonin Transporter Gene Variable Number Tandem Repeat in Intron 2 (STin2-VNTR) and Serotonin-Transporter-linked promoter region (5-HTTLPR), which have an influence over the functionality of SERT in the re-uptake and bioavailability of serotonin. The intestinal microbiota is a crucial actor in normal human gut physiology, exerting effects on serotonin, SERT function, and inflammatory processes. As a consequence of abnormal serotonin signaling and SERT function under these inflammatory processes, the use of selective serotonin re-uptake inhibitors (SSRIs) has been seen to improve disease activity and extraintestinal manifestations, such as depression and anxiety. The aim of this study is to integrate scientific data linking the intestinal microbiota as a regulator of gut serotonin signaling and re-uptake, as well as its role in the pathogenesis of IBD. We performed a narrative review, including a literature search in the PubMed database of both review and original articles (no date restriction), as well as information about the SLC6A4 gene and its genetic variants obtained from the Ensembl website. Scientific evidence from in vitro, in vivo, and clinical trials regarding the use of selective serotonin reuptake inhibitors as an adjuvant therapy in patients with IBD is also discussed. A total of 194 articles were used between reviews, in vivo, in vitro studies, and clinical trials.
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30
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Koustas E, Trifylli EM, Sarantis P, Papadopoulos N, Aloizos G, Tsagarakis A, Damaskos C, Garmpis N, Garmpi A, Papavassiliou AG, Karamouzis MV. Implication of gut microbiome in immunotherapy for colorectal cancer. World J Gastrointest Oncol 2022; 14:1665-1674. [PMID: 36187397 PMCID: PMC9516653 DOI: 10.4251/wjgo.v14.i9.1665] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Revised: 05/09/2022] [Accepted: 07/31/2022] [Indexed: 02/05/2023] Open
Abstract
Colorectal cancer (CRC) constitutes the third most frequently reported malignancy in the male population and the second most common in women in the last two decades. Colon carcinogenesis is a complex, multifactorial event, resulting from genetic and epigenetic aberrations, the impact of environmental factors, as well as the disturbance of the gut microbial ecosystem. The relationship between the intestinal microbiome and carcinogenesis was relatively undervalued in the last decade. However, its remarkable effect on metabolic and immune functions on the host has been in the spotlight as of recent years. There is a strong relationship between gut microbiome dysbiosis, bowel pathogenicity and responsiveness to anti-cancer treatment; including immunotherapy. Modifications of bacteriome consistency are closely associated with the immunologic response to immunotherapeutic agents. This condition that implies the necessity of gut microbiome manipulation. Thus, creatingan optimal response for CRC patients to immunotherapeutic agents. In this paper, we will review the current literature observing how gut microbiota influence the response of immunotherapy on CRC patients.
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Affiliation(s)
- Evangelos Koustas
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Eleni-Myrto Trifylli
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Panagiotis Sarantis
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Nikolaos Papadopoulos
- 1st Department of Internal Medicine, 417 Army Share Fund Hospital of Athens, Athens 11521, Attica, Greece
| | - Georgios Aloizos
- 1st Department of Internal Medicine, 417 Army Share Fund Hospital of Athens, Athens 11521, Attica, Greece
| | | | - Christos Damaskos
- N.S. Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Nikolaos Garmpis
- Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Anna Garmpi
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Athanasios G Papavassiliou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Michalis V Karamouzis
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
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31
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Human umbilical cord-derived mesenchymal stem cells ameliorate experimental colitis by normalizing the gut microbiota. STEM CELL RESEARCH & THERAPY 2022; 13:475. [PMID: 36104756 PMCID: PMC9476645 DOI: 10.1186/s13287-022-03118-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 08/04/2022] [Indexed: 11/26/2022]
Abstract
Background Crohn's disease (CD) is a chronic non-specific inflammatory bowel disease. Current CD therapeutics cannot fundamentally change the natural course of CD. Therefore, it is of great significance to find new treatment strategies for CD. Preclinical and clinical studies have shown that mesenchymal stromal cells (MSCs) are a promising therapeutic approach. However, the mechanism by which MSCs alleviate CD and how MSCs affect gut microbes are still unclear and need further elucidation. Methods We used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis in mice and analysed the microbiota in faecal samples from the control group, the TNBS group and the TNBS + MSC group with faecal 16S rDNA sequencing. Subsequent analyses of alpha and beta diversity were all performed based on the rarified data. PICRUStII analysis was performed on the 16S rRNA gene sequences to infer the gut microbiome functions. Results MSC Treatment improved TNBS-induced colitis by increasing survival rates and relieving symptoms. A distinct bacterial signature was found in the TNBS group that differed from the TNBS + MSC group and controls. MSCs prevented gut microbiota dysbiosis, including increasing α-diversity and the amount of Bacteroidetes Firmicutes and Tenericutes at the phylum level and decreasing the amount of Proteobacteria at the phylum level. MSCs alleviated the increased activities of sulphur and riboflavin metabolism. Meanwhile some metabolic pathways such as biosynthesis of amino acids lysine biosynthesis sphingolipid metabolism and secondary bile acid biosynthesis were decreased in the TNBS group compared with the control group and the TNBS + MSC group Conclusions Overall, our findings preliminarily confirmed that colitis in mice is closely related to microbial and metabolic dysbiosis. MSC treatment could modulate the dysregulated metabolism pathways in mice with colitis, restoring the abnormal microbiota function to that of the normal control group. This study provides insight into specific intestinal microbiota and metabolism pathways linked with MSC treatment, suggesting a new approach to the treatment of CD. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-03118-1.
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32
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Wang S, Godschalk R, Spooren C, de Graaf M, Jonkers D, van Schooten FJ. The role of diet in genotoxicity of fecal water derived from IBD patients and healthy controls. Food Chem Toxicol 2022; 168:113393. [PMID: 36049593 DOI: 10.1016/j.fct.2022.113393] [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: 04/21/2022] [Revised: 07/27/2022] [Accepted: 08/24/2022] [Indexed: 11/17/2022]
Abstract
Certain dietary factors with anti-inflammatory and/or anti-cancer properties would be a promising preventive strategy for inflammatory bowel disease (IBD) patients against developing colitis-associated colorectal cancer (CAC). In this study, fecal water (FW) was obtained from 80 IBD patients and 20 healthy controls (HCs). The comet assay was applied to determine the DNA damage induced by FW, and the protective potential of FW against hydrogen peroxide (H2O2) induced DNA damage in Caco-2 cells. Information on diet was obtained via food frequency questionnaires. The results showed that FW from IBD patients, especially patients with flares, induced higher levels of direct DNA damage in Caco-2 cells and showed less protection against H2O2-induced DNA damage, when compared to HCs. The DNA damage induced by FW was positively associated with consumption of processed meat and sugary foods, and nutrient intakes including heme iron and added sugars, whereas negatively correlated to intakes of soy products, and a dietary pattern characterized by high consumption of potatoes, white meat, nuts and seeds, eggs, legumes and soy products. FW from subjects with high coffee consumption protected against H2O2-induced DNA damage. These results can help to develop potential preventive strategies for IBD patients to reduce the CAC risk.
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Affiliation(s)
- Shan Wang
- Department of Pharmacology and Toxicology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
| | - Roger Godschalk
- Department of Pharmacology and Toxicology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
| | - Corinne Spooren
- Department of Internal Medicine, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands; Division of Gastroenterology-Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Marlijne de Graaf
- Department of Internal Medicine, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands; Division of Gastroenterology-Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Daisy Jonkers
- Department of Internal Medicine, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands; Division of Gastroenterology-Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Frederik-Jan van Schooten
- Department of Pharmacology and Toxicology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands.
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Malesza IJ, Bartkowiak-Wieczorek J, Winkler-Galicki J, Nowicka A, Dzięciołowska D, Błaszczyk M, Gajniak P, Słowińska K, Niepolski L, Walkowiak J, Mądry E. The Dark Side of Iron: The Relationship between Iron, Inflammation and Gut Microbiota in Selected Diseases Associated with Iron Deficiency Anaemia—A Narrative Review. Nutrients 2022; 14:nu14173478. [PMID: 36079734 PMCID: PMC9458173 DOI: 10.3390/nu14173478] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 08/18/2022] [Accepted: 08/19/2022] [Indexed: 12/21/2022] Open
Abstract
Iron is an indispensable nutrient for life. A lack of it leads to iron deficiency anaemia (IDA), which currently affects about 1.2 billion people worldwide. The primary means of IDA treatment is oral or parenteral iron supplementation. This can be burdened with numerous side effects such as oxidative stress, systemic and local-intestinal inflammation, dysbiosis, carcinogenic processes and gastrointestinal adverse events. Therefore, this review aimed to provide insight into the physiological mechanisms of iron management and investigate the state of knowledge of the relationship between iron supplementation, inflammatory status and changes in gut microbiota milieu in diseases typically complicated with IDA and considered as having an inflammatory background such as in inflammatory bowel disease, colorectal cancer or obesity. Understanding the precise mechanisms critical to iron metabolism and the awareness of serious adverse effects associated with iron supplementation may lead to the provision of better IDA treatment. Well-planned research, specific to each patient category and disease, is needed to find measures and methods to optimise iron treatment and reduce adverse effects.
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Affiliation(s)
- Ida J. Malesza
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | | | - Jakub Winkler-Galicki
- Department of Physiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Aleksandra Nowicka
- Department of Physiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | | | - Marta Błaszczyk
- Department of Physiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Paulina Gajniak
- Department of Physiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Karolina Słowińska
- Department of Physiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Leszek Niepolski
- Department of Physiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Jarosław Walkowiak
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Edyta Mądry
- Department of Physiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland
- Correspondence:
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Younis NK, Roumieh R, Bassil EP, Ghoubaira JA, Kobeissy F, Eid AH. Nanoparticles: attractive tools to treat colorectal cancer. Semin Cancer Biol 2022; 86:1-13. [DOI: 10.1016/j.semcancer.2022.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 08/17/2022] [Accepted: 08/19/2022] [Indexed: 10/31/2022]
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Chatterjee K, Dutta AK, Goel A, Aaron R, Balakrishnan V, Thomas A, John A, Jaleel R, David D, Kurien RT, Chowdhury SD, Simon EG, Joseph AJ, Premkumar P, Pulimood AB. Common polymorphisms of protein tyrosine phosphate non-receptor type 2 gene are not associated with risk of Crohn’s disease in Indian. World J Gastrointest Pathophysiol 2022; 13:114-123. [PMID: 36161231 PMCID: PMC9350595 DOI: 10.4291/wjgp.v13.i4.114] [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: 01/17/2022] [Revised: 03/18/2022] [Accepted: 05/23/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Multiple genetic risk factors for Crohn’s disease (CD) have been identified. However, these observations are not consistent across different populations. The protein tyrosine phosphate non-receptor type 2 (PTPN2) gene plays a role in various aspects of host defense including epithelial barrier function, autophagy, and innate and adaptive immune response. Two common polymorphisms in the PTPN2 gene (rs2542151 and rs7234029) have been associated with risk of CD in Western countries.
AIM To evaluate the association of PTPN2 gene polymorphisms with risk of CD in Indian population.
METHODS We conducted a prospective case-control study. Patients with CD were recruited, and their clinical and investigation details were noted. Controls were patients without organic gastrointestinal disease or other comorbid illnesses. Two common polymorphisms in the PTPN2 gene (rs2542151 and rs7234029) were assessed. DNA was extracted from peripheral blood samples of cases and controls and target DNA was amplified using specific sets of primers. The amplified fragments were digested with restriction enzymes and the presence of polymorphism was detected by restriction fragment length polymorphism. The frequency of alleles was determined. The frequencies of genotypes and alleles were compared between cases and controls to look for significant differences.
RESULTS A total of 108 patients with CD (mean age 37.5 ± 12.7 years, females 42.6%) and 100 controls (mean age 39.9 ± 13.5 years, females 37%) were recruited. For the single nucleotide polymorphism (SNP) rs7234029, the overall frequency of G variant genotype (AG or GG) was noted to be significantly lower in the cases compared to controls (35.2% vs 50%, P = 0.05). For the SNP rs2542151, the overall frequency of G variant genotype (GT or GG) was noted to be similar in cases compared to controls (43.6% vs 47%, P = 0.73). There were no significant differences in minor allele (G) frequency for both polymorphisms between the cases and controls. Both the SNPs had no significant association with age of onset of illness, gender, disease location, disease behaviour, perianal disease, or extraintestinal manifestations of CD.
CONCLUSION Unlike observation form the West, polymorphisms in the PTPN2 gene (rs7234029 and rs2542151) are not associated with an increased risk of developing CD in Indian patients.
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Affiliation(s)
- Kaushik Chatterjee
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Amit Kumar Dutta
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Ashish Goel
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Rekha Aaron
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Vijayalekshmi Balakrishnan
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Ajith Thomas
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Anoop John
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Rajeeb Jaleel
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Deepu David
- Department of Gastroenterology, Christian Medical College, Vellore 632004, Tamil Nadu, India
| | - Reuben Thomas Kurien
- Department of Gastroenterology, Christian Medical College, Vellore 632004, Tamil Nadu, India
| | - SD Chowdhury
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Ebby George Simon
- Department of Gastroenterology, Christian Medical College, Vellore 632004, Tamil Nadu, India
| | - AJ Joseph
- Department of Gastroenterology, Christian Medical College, Vellore 632004, Tamil Nadu, India
| | - Prasanna Premkumar
- Departments of Biostatistics, Christian Medical College, Vellore 632004, Tamil Nadu, India
| | - Anna B Pulimood
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
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Study of Correlation between Intestinal Microbiota and Traditional Chinese Medicine Syndrome of Patients with Colon Cancer. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:2989456. [PMID: 35859998 PMCID: PMC9293549 DOI: 10.1155/2022/2989456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 06/07/2022] [Indexed: 12/24/2022]
Abstract
Objective This research aims to study the material basis of the formation and specific bacteria of traditional Chinese medicine (TCM) syndrome from the characteristics of the intestinal microbiota of patients with colon cancer (CC) before and after the operation. Methods A cross-sectional study was conducted on 84 patients with CC and 24 healthy controls. A total of 168 and 24 stool samples were collected from CC patients before and after the operation and healthy controls. DNA was extracted from 192 stool samples and then amplified using PCR. The V3-V4 high variable areas were analyzed by 16s rDNA sequencing. Results The community diversity, in descending order, was the healthy control group and postoperative and preoperative groups of CC patients. The abundance of beneficial bacteria was postoperative group of CC patients > healthy control group > preoperative group of CC patients. Among the comparisons of the intestinal microbiota of preoperative groups of CC patients with different TCM syndromes, the community diversity in descending order was damp heat accumulation (DHA), spleen deficiency and dampness (SDD), spleen and kidney yang deficiency (SKYD), liver and kidney yin deficiency (LKYD), and deficiency of qi and blood (QBD), respectively. Specific microbiome analysis showed that the differences in the abundance of 42 taxons were statistically significant among the preoperative groups of CC patients with the five TCM syndromes and the healthy control group. While comparing the intestinal microbiota of postoperative groups with the five TCM syndromes, the community diversity in descending order is DHA, SDD, LKYD, SKYD, and QBD. Specific microbiome analysis showed that the differences in the abundance of 46 taxons were statistically significant among the postoperative groups of CC patients with the five TCM syndromes and the healthy control group. Streptococcus and Streptococcus mutans showed no statistical significance between the preoperative group and postoperative groups of CC with DHA syndrome (P > 0.05). Bacteroides at phylum and genus levels showed that there was no statistical significance between the preoperative group and the postoperative group of CC with SKYD syndrome (P > 0.05). Conclusions Before and after surgery, with the deterioration of TCM syndrome: DHA ⟶ SDD ⟶ SKYD ⟶ LKYD ⟶ QBD, the number of beneficial bacteria in CC patients' intestines decreased while the number of pathogenic bacteria increased, and the community structure of intestinal microbiota tends to be unitized, indicating a serious intestinal microbiological disorder. After radical surgery and perioperative intervention, the intestinal microbiota diversity and community structure of postoperative CC patients were closer to those of healthy people than preoperative. However, they were still imbalanced. The intestinal microbiota of CC patients with different TCM syndromes differs significantly, which is important for understanding the pathogenesis of CC in TCM. The DHA and SKYD syndromes in CC patients before and after surgery showed significant differences in the microbial structure. Streptococcus and Streptococcus mutans were the specific species with a significant difference in CC patients with DHA syndrome, while bacteroides were the specific species in CC patients with SKYD syndrome.
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Akiyama S, Fukuda S, Steinberg JM, Suzuki H, Tsuchiya K. Characteristics of inflammatory bowel diseases in patients with concurrent immune-mediated inflammatory diseases. World J Gastroenterol 2022; 28:2843-2853. [PMID: 35978883 PMCID: PMC9280738 DOI: 10.3748/wjg.v28.i25.2843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 03/10/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
Patients with inflammatory bowel disease (IBD) are more likely to have concurrent immune-mediated inflammatory diseases (IMIDs) than those without IBD. IMIDs have been observed to alter the phenotype and outcomes of IBD in recent studies. Several studies have found that IBD patients with concurrent IMIDs may have more extensive or severe disease phenotypes, and are considered to be at increased risk of requiring biologics and IBD-related surgeries, suggesting that having multiple IMIDs is a poor prognostic factor for IBD. Furthermore, IBD patients with primary sclerosing cholangitis and Takayasu arteritis are reported to have unique endoscopic phenotypes, suggesting concurrent IMIDs can influence IBD phenotype with specific intestinal inflammatory distributions. In this review, we discuss the pathogenesis, disease phenotypes, and clinical outcomes in IBD patients with concomitant IMIDs.
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Affiliation(s)
- Shintaro Akiyama
- Department of Gastroenterology, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
| | - Soma Fukuda
- Department of Gastroenterology, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
| | - Joshua M Steinberg
- Inflammatory Bowel Disease, Gastroenterology of the Rockies, Denver, CO 80218, United States
| | - Hideo Suzuki
- Department of Gastroenterology, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
| | - Kiichiro Tsuchiya
- Department of Gastroenterology, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
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Xu X, Ocansey DKW, Hang S, Wang B, Amoah S, Yi C, Zhang X, Liu L, Mao F. The gut metagenomics and metabolomics signature in patients with inflammatory bowel disease. Gut Pathog 2022; 14:26. [PMID: 35729658 PMCID: PMC9215062 DOI: 10.1186/s13099-022-00499-9] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 05/17/2022] [Indexed: 12/26/2022] Open
Abstract
Inflammatory bowel disease (IBD), a chronic gut immune dysregulation and dysbiosis condition is rapidly increasing in global incidence. Regardless, there is a lack of ideal diagnostic markers, while conventional treatment provides scarce desired results, thus, the exploration for better options. Changes in the gut microbial composition and metabolites either lead to or are caused by the immune dysregulation that characterizes IBD. This study examined the fecal metagenomics and metabolomic changes in IBD patients. A total of 30 fecal samples were collected from 15 IBD patients and 15 healthy controls for 16S rDNA gene sequencing and UHPLC/Q-TOF-MS detection of metabolomics. Results showed that there was a severe perturbation of gut bacteria community composition, diversity, metabolites, and associated functions and metabolic pathways in IBD. This included a significantly decreased abundance of Bacteroidetes and Firmicutes, increased disease-associated phyla such as Proteobacteria and Actinobacteria, and increased Escherichiacoli and Klebsiellapneumoniae in IBD. A total of 3146 metabolites were detected out of which 135 were differentially expressed between IBD and controls. Metabolites with high sensitivity and specificity in differentiating IBD from healthy individuals included 6,7,4′-trihydroxyisoflavone and thyroxine 4′-o-.beta.-d-glucuronide (AUC = 0.92), normorphine and salvinorin a (AUC = 0.90), and trichostachine (AUC = 0.91). Moreover, the IBD group had significantly affected pathways including primary bile acid biosynthesis, vitamin digestion and absorption, and carbohydrate metabolism. This study reveals that the combined evaluation of metabolites and fecal microbiome can be useful to discriminate between healthy subjects and IBD patients and consequently serve as therapeutic and diagnostic targets.
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Affiliation(s)
- Xinwei Xu
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, People's Republic of China
| | - Dickson Kofi Wiredu Ocansey
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, People's Republic of China.,Directorate of University Health Services, University of Cape Coast, PMB, Cape Coast, Ghana
| | - Sanhua Hang
- The People's Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Zhenjiang, 212300, Jiangsu, People's Republic of China
| | - Bo Wang
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, People's Republic of China
| | - Samuel Amoah
- Directorate of University Health Services, University of Cape Coast, PMB, Cape Coast, Ghana
| | - Chengxue Yi
- School of Medical Technology, Zhenjiang College, Zhenjiang, 212028, Jiangsu, People's Republic of China
| | - Xu Zhang
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, People's Republic of China
| | - Lianqin Liu
- Huai'an Maternity and Children Hospital, Huaian, 223002, Jiangsu, People's Republic of China.
| | - Fei Mao
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, People's Republic of China.
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Chen HM, MacDonald JA. Molecular Network Analyses Implicate Death-Associated Protein Kinase 3 (DAPK3) as a Key Factor in Colitis-Associated Dysplasia Progression. Inflamm Bowel Dis 2022; 28:1485-1496. [PMID: 35604388 PMCID: PMC9527615 DOI: 10.1093/ibd/izac098] [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] [Received: 10/31/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Ulcerative colitis (UC) is a progressive disorder that elevates the risk of colon cancer development through a colitis-dysplasia-carcinoma sequence. Gene expression profiling of colitis-associated lesions obtained from patients with varied extents of UC can be mined to define molecular panels associated with colon cancer development. METHODS Differential gene expression profiles of 3 UC clinical subtypes and healthy controls were developed for the GSE47908 microarray data set of healthy controls, left-sided colitis, pancolitis, and colitis-associated dysplasia (CAD) using limma R. RESULTS A gene ontology enrichment analysis of differentially expressed genes (DEGs) revealed a shift in the transcriptome landscape as UC progressed from left-sided colitis to pancolitis to CAD, from being immune-centric to being cytoskeleton-dependent. Hippo signaling (via Yes-associated protein [YAP]) and Ephrin receptor signaling were the top canonical pathways progressively altered in concert with the pathogenic progression of UC. A molecular interaction network analysis of DEGs in left-sided colitis, pancolitis, and CAD revealed 1 pairwise line, or edge, that was topologically important to the network structure. This edge was found to be highly enriched in actin-based processes, and death-associated protein kinase 3 (DAPK3) was a critical member and sole protein kinase member of this network. Death-associated protein kinase 3 is a regulator of actin-cytoskeleton reorganization that controls proliferation and apoptosis. Differential correlation analyses revealed a negative correlation for DAPK3-YAP in healthy controls that flipped to positive in left-sided colitis. With UC progression to CAD, the DAPK3-YAP correlation grew progressively more positive. CONCLUSION In summary, DAPK3 was identified as a candidate gene involved in UC progression to dysplasia.
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Affiliation(s)
- Huey-Miin Chen
- Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Justin A MacDonald
- Address correspondence to: Justin A. MacDonald, PhD, Department of Biochemistry & Molecular Biology, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6 ()
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Le Naour J, Sztupinszki Z, Carbonnier V, Casiraghi O, Marty V, Galluzzi L, Szallasi Z, Kroemer G, Vacchelli E. A loss-of-function polymorphism in ATG16L1 compromises therapeutic outcome in head and neck carcinoma patients. Oncoimmunology 2022; 11:2059878. [PMID: 35481288 PMCID: PMC9037530 DOI: 10.1080/2162402x.2022.2059878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
The anticancer immune response is shaped by immunogenic cell stress and death pathways. Thus, cancer cells can release danger-associated molecular patterns that act on pattern recognition receptors expressed by dendritic cells and their precursors to elicit an antitumor immune response. Here, we investigated the impact of single nucleotide polymorphisms (SNPs) in genes affecting this cancer-immunity dialogue in the context of head and neck squamous cell carcinoma (HNSCC). We observed that homozygosity for a loss-of-function SNP (rs2241880, leading to the substitution of a threonine residue in position 300 by an alanine) affecting autophagy related 16 like 1 (ATG16L1) is coupled to poor progression-free survival in platinum-treated HNSCC patients. This result was obtained on a cohort of patients enrolled at the Gustave Roussy Cancer Campus and was validated on an independent cohort of The Cancer Genome Atlas (TCGA). Homozygosity in rs2241880 is well known to predispose to Crohn’s disease, and epidemiological associations between Crohn’s disease and HNSCC have been reported at the levels of cancer incidence and prognosis. We speculate that rs2241880 might be partially responsible for this association.
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Affiliation(s)
- Julie Le Naour
- Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, Institut Universitaire de France, Paris, France
- Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
- Université Paris Sud, Paris Saclay, Faculty of Medicine Kremlin Bicêtre, France
| | - Zsofia Sztupinszki
- Computational Health Informatics Program (CHIP), Boston Children’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
- Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Vincent Carbonnier
- Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, Institut Universitaire de France, Paris, France
- Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
- Université Paris Sud, Paris Saclay, Faculty of Medicine Kremlin Bicêtre, France
| | - Odile Casiraghi
- Department of Head and Neck Surgical and Medical Oncology, Gustave Roussy Cancer Campus, Paris-Saclay University, Villejuif, France
| | - Virginie Marty
- Experimental and Translational Pathology Platform (PETRA), AMMICa Inserm US23/UMS CNRS3655, Gustave Roussy Cancer Campus, Villejuif, France
| | - Lorenzo Galluzzi
- Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA
- Sandra and Edward Meyer Cancer Center, New York, NY, USA
- Caryl and Israel Englander Institute for Precision Medicine, New York, NY, USA
| | - Zoltan Szallasi
- Computational Health Informatics Program (CHIP), Boston Children’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
- Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Guido Kroemer
- Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, Institut Universitaire de France, Paris, France
- Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
- Institut du Cancer Paris CARPEMAP-HP, Hôpital Européen Georges Pompidou, Pôle de Biologie, Paris, France
- Department of Cancer Medicine, Gustave Roussy Cancer Campus, Villejuif, France
| | - Erika Vacchelli
- Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, Institut Universitaire de France, Paris, France
- Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
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Protective Effects of Fermented Soybeans ( Cheonggukjang) on Dextran Sodium Sulfate (DSS)-Induced Colitis in a Mouse Model. Foods 2022; 11:foods11060776. [PMID: 35327199 PMCID: PMC8947378 DOI: 10.3390/foods11060776] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 03/04/2022] [Accepted: 03/07/2022] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease, and the incidence of IBD is increasing every year owing to changes in dietary structure. Although the exact pathogenesis of IBD is still unclear, recent evidence suggests that gut dysbiosis is closely associated with IBD pathogenesis. Cheonggukjang is a traditional Korean fermented soybean paste produced using traditional and industrial methods, and contains probiotics, which affect the gut microbiota composition. However, the protective effect of Cheonggukjang against IBD is unknown. In this study, we investigated the bacterial community structure of traditional and commercial Cheonggukjang samples, as well as the protective effect of Cheonggukjang on a dextran sulfate sodium (DSS)-induced colitis mouse model. Traditional and commercial Cheonggukjang were found to contain various type of useful probiotics in their bacterial community structure. Cheonggukjang reduced the progression of DSS-induced symptoms, such as body weight loss, colonic shortening, disease activity index, and histological changes. Further, Cheonggukjang improved the intestinal epithelial barrier integrity on DSS-induced colitis mice. In addition, Cheonggukjang suppressed the expression of proinflammatory cytokines and inflammatory mediators through the inactivation of NF-κB and MAPK signaling pathways. These results indicate that Cheonggukjang exerts protective effects against DSS-induced colitis, suggesting its possible application as a functional food for improving inflammatory diseases.
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Wang CPJ, Byun MJ, Kim SN, Park W, Park HH, Kim TH, Lee JS, Park CG. Biomaterials as therapeutic drug carriers for inflammatory bowel disease treatment. J Control Release 2022; 345:1-19. [DOI: 10.1016/j.jconrel.2022.02.028] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 02/20/2022] [Accepted: 02/21/2022] [Indexed: 12/13/2022]
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Association of Interleukin Genes IL10 and IL10RB with Parameters of Overweight in Military Students. Genes (Basel) 2022; 13:genes13020291. [PMID: 35205336 PMCID: PMC8871646 DOI: 10.3390/genes13020291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 01/29/2022] [Accepted: 01/29/2022] [Indexed: 02/01/2023] Open
Abstract
Background: To date, nearly 300 single-nucleotide polymorphisms (SNPs) associated with BMI, waist-to-hip ratio, and other adiposity traits have been identified by GWAS. With regards to IL10, at least 49 IL10-associated polymorphisms have been reported. However, little is known regarding the relationship between SNPs of the IL10 gene and the risk of obesity in young men. The aim of the present study was to investigate the relationship between SNPs of the IL10 and IL10RB genes and the risk of obesity in young men. Methods: A cohort of 139 male students were enrolled and the following IL10 and IL10RB SNPs were analyzed: IL10 (rs1518110), IL10 (rs3024491), IL10RB (rs2834167). The subjects were divided into groups depending on obesity parameters: body mass index (BMI), fat mass index (FMI) and fat percentage (Fat%). Statistical analysis was conducted for a single locus and haplotypes, an association between SNPs and body composition parameters was tested with four genetic models: dominant, recessive, codominant and overdominant mode of inheritance (MOI). Results: Significant association was found for interaction IL10 (rs1518110) × IL10RB (rs2834167) with Fat% value exceeding 20 in codominant (p-value = 0.03, OR = 0.34, 95% CI 0.08 1.44) and dominant model (p-value = 0.03, OR = 0.34, 95% CI 0.08 1.44) Conclusion: Our study shows for the first time that there is a correlation between the occurrence of specific polymorphisms of IL10 gene (rs1518110, rs3024491 and rs2834167) and the possibility of obesity.
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Markandey M, Bajaj A, Ilott NE, Kedia S, Travis S, Powrie F, Ahuja V. Gut microbiota: sculptors of the intestinal stem cell niche in health and inflammatory bowel disease. Gut Microbes 2022; 13:1990827. [PMID: 34747326 PMCID: PMC8583176 DOI: 10.1080/19490976.2021.1990827] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Intestinal epithelium represents a dynamic and diverse cellular system that continuously interacts with gut commensals and external cues. Intestinal stem cells, which lie at the heart of epithelial renewal and turnover, proliferate to maintain a steady stem cell population and differentiate to form functional epithelial cell types. This rather sophisticated assembly-line is maintained by an elaborate micro-environment, sculpted by a myriad of host and gut microbiota-derived signals, forming an intestinal stem cell niche. This complex, yet crucial signaling niche undergoes dynamic changes during homeostasis and chronic intestinal inflammation. Inflammatory bowel disease refers to a chronic inflammatory response toward pathogenic or commensal microbiota, in a genetically susceptible host. Compositional and functional alterations in gut microbiota are pathognomonic of IBD.The present review highlights the modulatory role of gut microbiota on the intestinal stem cell niche during homeostasis and inflammatory bowel disease. We discuss the mechanisms of direct action of gut commensals (through microbiota-derived or microbiota-influenced metabolites) on ISCs, followed by their effects via other epithelial and immune cell types.
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Affiliation(s)
- Manasvini Markandey
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Aditya Bajaj
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | | | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Simon Travis
- Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Fiona Powrie
- Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India,CONTACT Vineet Ahuja Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India, 110029
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Pareek S, Sanchenkova X, Sakaguchi T, Murakami M, Okumura R, Kayama H, Kawauchi S, Motooka D, Nakamura S, Okuzaki D, Kishimoto T, Takeda K. Epithelial miR‐215 negatively modulates Th17‐dominant inflammation by inhibiting CXCL12 production in the small intestine. Genes Cells 2022; 27:243-253. [DOI: 10.1111/gtc.12922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/17/2022] [Accepted: 01/20/2022] [Indexed: 11/27/2022]
Affiliation(s)
- Siddhika Pareek
- Regenerative Medicine Institute Cedars‐Sinai Medical Center Los Angeles CA 90048 USA
| | - Xenia Sanchenkova
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
| | - Taiki Sakaguchi
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Laboratory of Immune Regulation Department of Microbiology and Immunology Graduate School of Medicine Osaka University Osaka 5650871 Japan
| | - Mari Murakami
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Laboratory of Immune Regulation Department of Microbiology and Immunology Graduate School of Medicine Osaka University Osaka 5650871 Japan
| | - Ryu Okumura
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Laboratory of Immune Regulation Department of Microbiology and Immunology Graduate School of Medicine Osaka University Osaka 5650871 Japan
| | - Hisako Kayama
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Laboratory of Immune Regulation Department of Microbiology and Immunology Graduate School of Medicine Osaka University Osaka 5650871 Japan
- Institute for Advanced Co‐Creation Studies Osaka University Osaka 5650871 Japan
| | - Saya Kawauchi
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Laboratory of Immune Regulation Department of Microbiology and Immunology Graduate School of Medicine Osaka University Osaka 5650871 Japan
| | - Daisuke Motooka
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Genome Information Research Center Research Institute for Microbial Diseases Osaka University Osaka 5650871 Japan
| | - Shota Nakamura
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Genome Information Research Center Research Institute for Microbial Diseases Osaka University Osaka 5650871 Japan
| | - Daisuke Okuzaki
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Genome Information Research Center Research Institute for Microbial Diseases Osaka University Osaka 5650871 Japan
| | - Tadamitsu Kishimoto
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
| | - Kiyoshi Takeda
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Laboratory of Immune Regulation Department of Microbiology and Immunology Graduate School of Medicine Osaka University Osaka 5650871 Japan
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El-Sahhar S, Varga-Weisz P. The gut microbiome in health and disease: Inflammatory bowel diseases. ADV ECOL RES 2022. [DOI: 10.1016/bs.aecr.2022.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Exosomes as a New Delivery Vehicle in Inflammatory Bowel Disease. Pharmaceutics 2021; 13:pharmaceutics13101644. [PMID: 34683937 PMCID: PMC8539337 DOI: 10.3390/pharmaceutics13101644] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 09/29/2021] [Accepted: 10/01/2021] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a type of chronic relapsing inflammatory disease. The pathogenesis of IBD is still unclear, which may involve environmental factors, genetic factors, intestinal microbiota disorder, and abnormal immune responses. Exosomes (30–150 nm) are found in various body fluids, including blood, saliva, urine, and cerebrospinal fluid. Exosomes mediate intercellular communication and regulate cell biological activity by carrying non-coding RNAs, proteins, and lipids. There is evidence that exosomes are involved in the pathogenesis of IBD. In view of the important roles of exosomes in the pathogenesis of IBD, this work systematically reviews the latest research progress of exosomes in IBD, especially the roles of exosomes as non-coding RNA delivery systems in the pathogenesis of IBD, including a disordered immune response, barrier function, and intestinal microbiota. The review will help to clarify the pathogenesis of IBD and explore new diagnostic markers and therapeutic targets for patients with IBD.
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Zou J, Liu C, Jiang S, Qian D, Duan J. Cross Talk between Gut Microbiota and Intestinal Mucosal Immunity in the Development of Ulcerative Colitis. Infect Immun 2021; 89:e0001421. [PMID: 33526559 PMCID: PMC8370674 DOI: 10.1128/iai.00014-21] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis (UC), a nonspecific inflammatory disease, is characterized by inflammation and mucosal damage in the colon, and its prevalence in the world is increasing. Nevertheless, the exact pathogenesis of UC is still unclear. Accumulating data have suggested that its pathogenesis is multifactorial, involving genetic predisposition, environmental factors, microbial dysbiosis, and dysregulated immune responses. Generally, UC is aroused by inappropriate immune activation based on the interaction of host and intestinal microbiota. The relationship between microbiota and host immune system in the pathogenesis of UC is complicated. However, increasing evidence indicates that the shift of microbiota composition can substantially influence intestinal immunity. In this review, we primarily focus on the delicate balance between microbiota and gut mucosal immunity during UC progression.
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Affiliation(s)
- Junfeng Zou
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Chen Liu
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Shu Jiang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Dawei Qian
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Jinao Duan
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
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Antunes JC, Seabra CL, Domingues JM, Teixeira MO, Nunes C, Costa-Lima SA, Homem NC, Reis S, Amorim MTP, Felgueiras HP. Drug Targeting of Inflammatory Bowel Diseases by Biomolecules. NANOMATERIALS 2021; 11:nano11082035. [PMID: 34443866 PMCID: PMC8401460 DOI: 10.3390/nano11082035] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 07/29/2021] [Accepted: 08/05/2021] [Indexed: 02/06/2023]
Abstract
Inflammatory bowel disease (IBD) is a group of disabling, destructive and incurable immune-mediated inflammatory diseases comprising Crohn’s disease (CD) and ulcerative colitis (UC), disorders that are highly prevalent worldwide and demand a large investment in healthcare. A persistent inflammatory state enables the dysfunction and destruction of healthy tissue, hindering the initiation and endurance of wound healing. Current treatments are ineffective at counteracting disease progression. Further, increased risk of serious side effects, other comorbidities and/or opportunistic infections highlight the need for effective treatment options. Gut microbiota, the key to preserving a healthy state, may, alternatively, increase a patient’s susceptibility to IBD onset and development given a relevant bacterial dysbiosis. Hence, the main goal of this review is to showcase the main conventional and emerging therapies for IBD, including microbiota-inspired untargeted and targeted approaches (such as phage therapy) to infection control. Special recognition is given to existing targeted strategies with biologics (via monoclonal antibodies, small molecules and nucleic acids) and stimuli-responsive (pH-, enzyme- and reactive oxygen species-triggered release), polymer-based nanomedicine that is specifically directed towards the regulation of inflammation overload (with some nanosystems additionally functionalized with carbohydrates or peptides directed towards M1-macrophages). The overall goal is to restore gut balance and decrease IBD’s societal impact.
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Affiliation(s)
- Joana Costa Antunes
- Centre for Textile Science and Technology (2C2T), Campus de Azurém, University of Minho, 4800-058 Guimarães, Portugal; (J.M.D.); (M.O.T.); (N.C.H.); (M.T.P.A.); (H.P.F.)
- Correspondence: ; Tel.: +351-253-510-289
| | - Catarina Leal Seabra
- Laboratório Associado para a Química Verde (LAQV), Network of Chemistry and Technology (REQUIMTE), Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal; (C.L.S.); (C.N.); (S.A.C.-L.); (S.R.)
| | - Joana Margarida Domingues
- Centre for Textile Science and Technology (2C2T), Campus de Azurém, University of Minho, 4800-058 Guimarães, Portugal; (J.M.D.); (M.O.T.); (N.C.H.); (M.T.P.A.); (H.P.F.)
| | - Marta Oliveira Teixeira
- Centre for Textile Science and Technology (2C2T), Campus de Azurém, University of Minho, 4800-058 Guimarães, Portugal; (J.M.D.); (M.O.T.); (N.C.H.); (M.T.P.A.); (H.P.F.)
| | - Cláudia Nunes
- Laboratório Associado para a Química Verde (LAQV), Network of Chemistry and Technology (REQUIMTE), Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal; (C.L.S.); (C.N.); (S.A.C.-L.); (S.R.)
| | - Sofia Antunes Costa-Lima
- Laboratório Associado para a Química Verde (LAQV), Network of Chemistry and Technology (REQUIMTE), Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal; (C.L.S.); (C.N.); (S.A.C.-L.); (S.R.)
| | - Natália Cândido Homem
- Centre for Textile Science and Technology (2C2T), Campus de Azurém, University of Minho, 4800-058 Guimarães, Portugal; (J.M.D.); (M.O.T.); (N.C.H.); (M.T.P.A.); (H.P.F.)
| | - Salette Reis
- Laboratório Associado para a Química Verde (LAQV), Network of Chemistry and Technology (REQUIMTE), Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal; (C.L.S.); (C.N.); (S.A.C.-L.); (S.R.)
| | - Maria Teresa Pessoa Amorim
- Centre for Textile Science and Technology (2C2T), Campus de Azurém, University of Minho, 4800-058 Guimarães, Portugal; (J.M.D.); (M.O.T.); (N.C.H.); (M.T.P.A.); (H.P.F.)
| | - Helena Prado Felgueiras
- Centre for Textile Science and Technology (2C2T), Campus de Azurém, University of Minho, 4800-058 Guimarães, Portugal; (J.M.D.); (M.O.T.); (N.C.H.); (M.T.P.A.); (H.P.F.)
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华 慧, 董 昕, 张 雨, 方 凡, 张 蓓, 李 向, 于 倩, 郑 葵, 颜 超. [rCsHscB derived from Clonorchis sinensis has therapeutic effect on dextran sodium sulfate-induced chronic ulcerative colitis in mice]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2021; 41:664-670. [PMID: 34134952 PMCID: PMC8214966 DOI: 10.12122/j.issn.1673-4254.2021.05.05] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To investigate the therapeutic effect of rCsHscB derived from Clonorchis sinensis on dextran sodium sulfate (DSS)-induced chronic ulcerative colitis in mice. OBJECTIVE C57BL/6 mice were randomized into negative control (NC) group (n= 10), rCsHscB group (n=10), DSS group (n=15), and DSS+rCsHscB group (n=15), and in the latter two groups, chronic ulcerative colitis was induced in the mice using 2% DSS. In rCsHscB and DSS+ rCsHscB groups, the mice received intraperitoneal injections of 125 μg/mL rCsHscB on the 4th and 7th day following DSS administration, and PBS was injected in the other two groups. The mice were euthanized on the 84th day, and pathological changes of the colon were evaluated by HE and Masson staining. The levels of CD4+ and CD8+ T cells in the peripheral blood and lamina propria gastric lymphocytes (LPL) were analyzed by flow cytometer; the levels of IL-6, MCP-1 and IL-10 in colon homogenate were determined using ELISA, and the phosphorylation of ERK1/2, JNK and P38 was detected with Western blotting. OBJECTIVE Compared with those in NC group, the mice in rCsHscB group exhibited no adverse responses to the treatment. The mice in DSS group had severe pathologies in the colon with significantly increased ratios of CD4+ and CD4+/CD8+ T cells in peripheral blood and LPL, increased levels of IL-6 and MCP-1 but no obvious changes in IL-10 in colon homogenate, and significantly augmented phosphorylation levels of ERK1/2, JNK and P38. Compared with those in DSS group, the mice in DSS+ rCsHscB group showed ameliorated colon pathologies with decreased CD4+T/CD8+T cell ratio in the peripheral blood and LPL, significantly decreased IL-6 and MCP-1 levels and increased IL-10 in colon homogenate, and lowered phosphorylation levels of ERK1/2, JNK and P38. OBJECTIVE rCsHscB can produce therapeutic effect on DSS-induced chronic ulcerative colitis in mice possibly by inhibiting the production of pro-inflammatory factors and regulating the balance of CD4+/CD8+T cells through the MAPK pathway.
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Affiliation(s)
- 慧 华
- />徐州医科大学病原生物学与免疫学教研室，江苏省免疫与代谢重点实验室，徐州市感染与免疫重点实验室，江苏 徐州 221004Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Key Laboratory of Infection and Immunity, Department of Pathogen and Immunology, Xuzhou Medical University, Xuzhou 221004, China
| | - 昕 董
- />徐州医科大学病原生物学与免疫学教研室，江苏省免疫与代谢重点实验室，徐州市感染与免疫重点实验室，江苏 徐州 221004Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Key Laboratory of Infection and Immunity, Department of Pathogen and Immunology, Xuzhou Medical University, Xuzhou 221004, China
| | - 雨钊 张
- />徐州医科大学病原生物学与免疫学教研室，江苏省免疫与代谢重点实验室，徐州市感染与免疫重点实验室，江苏 徐州 221004Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Key Laboratory of Infection and Immunity, Department of Pathogen and Immunology, Xuzhou Medical University, Xuzhou 221004, China
| | - 凡 方
- />徐州医科大学病原生物学与免疫学教研室，江苏省免疫与代谢重点实验室，徐州市感染与免疫重点实验室，江苏 徐州 221004Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Key Laboratory of Infection and Immunity, Department of Pathogen and Immunology, Xuzhou Medical University, Xuzhou 221004, China
| | - 蓓蓓 张
- />徐州医科大学病原生物学与免疫学教研室，江苏省免疫与代谢重点实验室，徐州市感染与免疫重点实验室，江苏 徐州 221004Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Key Laboratory of Infection and Immunity, Department of Pathogen and Immunology, Xuzhou Medical University, Xuzhou 221004, China
| | - 向阳 李
- />徐州医科大学病原生物学与免疫学教研室，江苏省免疫与代谢重点实验室，徐州市感染与免疫重点实验室，江苏 徐州 221004Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Key Laboratory of Infection and Immunity, Department of Pathogen and Immunology, Xuzhou Medical University, Xuzhou 221004, China
| | - 倩 于
- />徐州医科大学病原生物学与免疫学教研室，江苏省免疫与代谢重点实验室，徐州市感染与免疫重点实验室，江苏 徐州 221004Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Key Laboratory of Infection and Immunity, Department of Pathogen and Immunology, Xuzhou Medical University, Xuzhou 221004, China
| | - 葵阳 郑
- />徐州医科大学病原生物学与免疫学教研室，江苏省免疫与代谢重点实验室，徐州市感染与免疫重点实验室，江苏 徐州 221004Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Key Laboratory of Infection and Immunity, Department of Pathogen and Immunology, Xuzhou Medical University, Xuzhou 221004, China
| | - 超 颜
- />徐州医科大学病原生物学与免疫学教研室，江苏省免疫与代谢重点实验室，徐州市感染与免疫重点实验室，江苏 徐州 221004Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Key Laboratory of Infection and Immunity, Department of Pathogen and Immunology, Xuzhou Medical University, Xuzhou 221004, China
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