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Qin X. Emerging Connections Between Inflammatory Bowel Disease Subtypes and Sequential Changes in Total Serum Bilirubin. Inflamm Bowel Dis 2025; 31:1475-1478. [PMID: 39832261 DOI: 10.1093/ibd/izaf004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Indexed: 01/22/2025]
Abstract
Lay Summary
Building on my long-standing hypothesis that impaired inactivation of digestive proteases by deconjugated bilirubin may be the unifying feature and mechanism of inflammatory bowel disease (IBD), this paper explores potential connections among different subtypes of IBD through sequential changes in total serum bilirubin.
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Song L, Deng Y, Huang J, Zhu X, Zhong Y, Zhong Q, Zhou W, Liu Y, Zhao H, Ge W, Liu D. Effect of curcumin regulated memory Th7 cells in mice with DSS-induced colitis. Int Immunopharmacol 2025; 145:113770. [PMID: 39642569 DOI: 10.1016/j.intimp.2024.113770] [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: 05/11/2024] [Revised: 11/03/2024] [Accepted: 11/30/2024] [Indexed: 12/09/2024]
Abstract
Abnormal activation or dysfunction of memory helper T (mTh) cells is closely associated with the development of ulcerative colitis (UC). Curcumin (Cur), the main component of turmeric, plays a critical role in the treatment of UC due to its favorable anti-inflammatory and immunomodulatory bioactivities. However, whether Cur modulates mTh7 cells to alleviate UC is unknown. In the present study, dextran sulphate sodium (DSS) was administered to establish a colitis model in mice. Our current findings indicated that Cur effectively ameliorated the manifestations of colitis in mice, and had a significant effect in reducing disease activity index (DAI), as well as in the colonic weight and the proportion of colonic weight to colonic length. While Cur reduced the pathological injuries of the colon, restore the length of the colon, inhibited the secretion of IL-7 and IL-21, restored the secretion of IL-2, IL-4, and IL-10. Furthermore, Cur had a regulatory effect on mTh7 cells and their subpopulation status. The results of molecular docking simulations and Surface Plasmon Resonance (SPR) indicated that Cur demonstrates strong interaction capabilities with both IL-7 and IL-7R and reduced the expression levels of IL-7/IL-7R mRNA and protein. It is suggested that the alleviation of DSS-induced colitis by Cur may be achieved by reducing the level of mTh7 cells and inhibiting the activation of IL-7/IL-7R signaling.
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Affiliation(s)
- Lizhao Song
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Yifei Deng
- Clinical Medical School, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Jiaqi Huang
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Xiyan Zhu
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Youbao Zhong
- Laboratory Animal Research Center for Science and Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Qin Zhong
- School of Nursing, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Wen Zhou
- Nanchang Medical College, Nanchang 330052, Jiangxi Province, China
| | - Yali Liu
- Nanchang Medical College, Nanchang 330052, Jiangxi Province, China
| | - Haimei Zhao
- Formula-Pattern Research Center of Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China.
| | - Wei Ge
- Department of Proctology, Affiliated Hospital of Jiangxi University of Chinese Medicine, 1688 Meiling Road, Nanchang 330004, Jiangxi Province, China.
| | - Duanyong Liu
- School of Nursing, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; Formula-Pattern Research Center of Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China.
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Ozaka S, Sonoda A, Kudo Y, Ito K, Kamiyama N, Sachi N, Chalalai T, Kagoshima Y, Soga Y, Ekronarongchai S, Ariki S, Mizukami K, Ishizawa S, Nishiyama M, Murakami K, Takeda K, Kobayashi T. Daikenchuto, a Japanese herbal medicine, ameliorates experimental colitis in a murine model by inducing secretory leukocyte protease inhibitor and modulating the gut microbiota. Front Immunol 2024; 15:1457562. [PMID: 39524440 PMCID: PMC11543465 DOI: 10.3389/fimmu.2024.1457562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 10/07/2024] [Indexed: 11/16/2024] Open
Abstract
Background Inflammatory bowel disease (IBD) is a refractory inflammatory disorder of the intestine, which is probably triggered by dysfunction of the intestinal epithelial barrier. Secretory leukocyte protease inhibitor (SLPI) secreted by colon epithelial cells protects against intestinal inflammation by exerting anti-protease and anti-microbial activities. Daikenchuto (DKT) is one of the most commonly prescribed Japanese traditional herbal medicines for various digestive diseases. Although several animal studies have revealed that DKT exerts anti-inflammatory effects, its detailed molecular mechanism is unclear. This study aimed to clarify the anti-inflammatory mechanism of DKT using a murine colitis model, and to evaluate its potential as a therapeutic agent for IBD. Methods Experimental colitis was induced in wild-type (WT) mice and SLPI-deficient (KO) mice by dextran sulfate sodium (DSS) after oral administration of DKT. The resultant clinical symptoms, histological changes, and pro-inflammatory cytokine levels in the colon were assessed. Expression of SLPI in the colon was detected by Western blotting and immunohistochemistry. Composition of the gut microbiota was analyzed by 16S rRNA metagenome sequencing and intestinal metabolites were measured by gas chromatography-mass spectrometry analysis. Intestinal epithelial barrier function was assessed by oral administration of FITC-dextran and immunostaining of tight junction proteins (TJPs). Results Oral administration of DKT increased the number of butyrate-producing bacteria, such as Parabacteroides, Allobaculum, and Akkermansia, enhanced the levels of short-chain fatty acids, including butyrate, in the colon, induced SLPI expression, and ameliorated DSS-induced colitis in WT mice. We found that mouse colon carcinoma cell line treatment with either DKT or butyrate significantly enhanced the expression of SLPI. Moreover, supplementation of DKT protected the intestinal epithelial barrier with augmented expression of TJPs in WT mice, but not in KO mice. Finally, the composition of the gut microbiota was changed by DKT in WT mice, but not in KO mice, suggesting that DKT alters the colonic bacterial community in an SLPI-dependent manner. Conclusion These results indicate that DKT exerts anti-inflammatory effects on the intestinal epithelial barrier by SLPI induction, due, at least in part, to increased butyrate-producing bacteria and enhanced butyrate levels in the colon. These results provide insight into the mechanism of the therapeutic effects of DKT on IBD.
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Affiliation(s)
- Sotaro Ozaka
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Akira Sonoda
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Yoko Kudo
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kanako Ito
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Naganori Kamiyama
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Nozomi Sachi
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Thanyakorn Chalalai
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Yomei Kagoshima
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Yasuhiro Soga
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | | | - Shimpei Ariki
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kazuhiro Mizukami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Shiori Ishizawa
- Tsumura Advanced Technology Research Laboratories, Research and Development Division, Tsumura & Co., Inashiki, Japan
| | - Mitsue Nishiyama
- Tsumura Advanced Technology Research Laboratories, Research and Development Division, Tsumura & Co., Inashiki, Japan
| | - Kazunari Murakami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kiyoshi Takeda
- Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan
| | - Takashi Kobayashi
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
- Research Center for GLOBAL and LOCAL Infectious Diseases, Oita University, Yufu, Japan
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Sharma S, Gilberto VS, Levens CL, Chatterjee A, Kuhn KA, Nagpal P. Microbiome- and Host Inflammasome-Targeting Inhibitor Nanoligomers Are Therapeutic in the Murine Colitis Model. ACS Pharmacol Transl Sci 2024; 7:2677-2693. [PMID: 39296260 PMCID: PMC11406689 DOI: 10.1021/acsptsci.4c00102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 07/30/2024] [Accepted: 08/20/2024] [Indexed: 09/21/2024]
Abstract
Autoimmune and autoinflammatory diseases account for more than 80 chronic conditions affecting more than 24 million people in the US. Among these autoinflammatory diseases, noninfectious chronic inflammation of the gastrointestinal (GI) tract causes inflammatory bowel diseases (IBDs), primarily Crohn's and ulcerative colitis (UC). IBD is a complex disease, and one hypothesis is that these are either caused or worsened by compounds produced by bacteria in the gut. While traditional approaches have focused on pan immunosuppressive techniques (e.g., steroids), low remission rates, prolonged illnesses, and an increased frequency of surgical procedures have prompted the search for more targeted and precision therapeutic approaches. IBD is a complex disease resulting from both genetic and environmental factors, but several recent studies have highlighted the potential pivotal contribution of gut microbiota dysbiosis. Gut microbiota are known to modulate the immune status of the gut by producing metabolites that are encoded in biosynthetic gene clusters (BGCs) of the bacterial genome. Here, we show a targeted and high-throughput screening of more than 90 biosynthetic genes in 41 gut anaerobes, through downselection using available bioinformatics tools, targeted gene manipulation in these genetically intractable organisms using the Nanoligomer platform, and identification and synthesis of top microbiome targets as a Nanoligomer BGC cocktail (SB_BGC_CK1, abbreviated as CK1) as a feasible precision therapeutic approach. Further, we used a host-directed immune target screening to identify the NF-κB and NLRP3 cocktail SB_NI_112 (or NI112 for short) as a targeted inflammasome inhibitor. We used these top two microbe- and host-targeted Nanoligomer cocktails in acute and chronic dextran sulfate sodium (DSS) mouse colitis and in TNFΔARE/+ transgenic mice that develop spontaneous Crohn's like ileitis. The mouse microbiome was humanized to replicate that in human IBD through antibiotic treatment, followed by mixed fecal gavage from 10 human donors and spiked with IBD-inducing microbial species. Following colonization, colitis was induced in mice using 1 week of 3% DSS (acute) or 6 weeks of 3 rounds of 2.5% DSS induction for a week followed by 1 week of no DSS (chronic colitis model). Both Nanoligomer cocktails (CK1 and NI112) showed a strong reduction in disease severity, significant improvement in disease histopathology, and profound downregulation of disease biomarkers in colon tissue, as assessed by multiplexed ELISA. Further, we used two different formulations of intraperitoneal injections (IP) and Nanoligomer pills in the chronic DSS colitis model. Although both formulations were highly effective, the oral pill formulation demonstrated a greater reduction in biochemical markers compared to IP. A similar therapeutic effect was observed in the TNFΔARE/+ model. Overall, these results point to the potential for further development and testing of this inflammasome-targeting host-directed therapy (NI112) and more personalized microbiome cocktails (CK1) for patients with recalcitrant IBD.
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Affiliation(s)
- Sadhana Sharma
- Sachi Bio, Colorado Technology Center, 685 S Arthur Avenue, Louisville, Colorado 8002, United States
| | - Vincenzo S Gilberto
- Sachi Bio, Colorado Technology Center, 685 S Arthur Avenue, Louisville, Colorado 8002, United States
| | - Cassandra L Levens
- Division of Rheumatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, United States
| | - Anushree Chatterjee
- Sachi Bio, Colorado Technology Center, 685 S Arthur Avenue, Louisville, Colorado 8002, United States
| | - Kristine A Kuhn
- Division of Rheumatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, United States
| | - Prashant Nagpal
- Sachi Bio, Colorado Technology Center, 685 S Arthur Avenue, Louisville, Colorado 8002, United States
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Danese S, Fiorino G, Vicaut E, Paridaens K, Ugur A, Clark B, Vanasek T, Stepek D, D'Amico F, West R, Gilissen LPL, Wisniewska Jarosinka M, Drobinski P, Fronik G, Fic M, Walczak M, Kowalski M, Korczowski B, Wiatr M, Peyrin-Biroulet L. Clinical Trial: A Pragmatic Randomised Controlled Study to Assess the Effectiveness of Two Patient Management Strategies in Mild to Moderate Ulcerative Colitis-The OPTIMISE Study. J Clin Med 2024; 13:5147. [PMID: 39274360 PMCID: PMC11395821 DOI: 10.3390/jcm13175147] [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: 07/24/2024] [Revised: 08/15/2024] [Accepted: 08/27/2024] [Indexed: 09/16/2024] Open
Abstract
Background: Current management of mild-to-moderate ulcerative colitis (UC) involves monitoring clinical markers of disease activity, such as stool frequency (SF) and rectal bleeding (RB), and adjusting treatment accordingly. Our aim was to assess whether targeting treatment based on faecal calprotectin (FC) levels (treat-to-target; T2T) provides greater UC disease control versus a symptom-based approach. Methods: This was a pragmatic, randomised (1:1) controlled study of patients with mild-to-moderate UC (global Mayo score 2-6) treated with ≤2.4 g/day 5-aminosalicylic acid that compared the effectiveness of two management strategies with (interventional arm) and without (reference arm) FC home monitoring over 12 months of follow-up. Treatment was optimised in the interventional arm using FC values and clinical symptoms (PRO-2), while the reference arm used only PRO-2. Results: 193 patients completed the study. No significant difference was found for the primary endpoint (Mayo Endoscopic Subscore [MES] = 0 at 12 months). A numerical advantage for the interventional arm over the reference arm for the primary endpoint (37.0% vs. 33.4%, respectively) and for MES ≤ 1, RB = 0, and SF ≤ 1 at 12 months was found following imputation for missing data. The composite endpoint of MES = 0, RB = 0, and SF ≤ 1 at 12 months was achieved at a significantly higher rate in the interventional arm than the reference arm (effect size [ES]: 0.17, 95% CI 0.02-0.32; p < 0.05). A similar result was obtained for MES ≤ 1, RB = 0 and SF ≤ 1 (ES: 0.22; 95% CI 0.07-0.37; p < 0.05). Conclusions: T2T using FC monitoring was effective in patients with mild-to-moderate UC at 12 months. Further longer-term studies are required to confirm the results.
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Affiliation(s)
- Silvio Danese
- Department of Gastroenterology and Digestive Endoscopy, San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Gionata Fiorino
- IBD Unit, Department of Gastroenterology and Digestive Endoscopy, San Camillo-Forlanini Hospital, 00152 Rome, Italy
| | - Eric Vicaut
- Clinical Trial Unit, Hospital Lariboisière APHP, 75010 Paris, France
| | | | - Asiya Ugur
- Ferring Pharmaceuticals A/S, 2770 Kastrup, Denmark
| | - Brian Clark
- Ferring Pharmaceuticals A/S, 2770 Kastrup, Denmark
| | - Tomas Vanasek
- Hepato-Gastroenterologie HK, s.r.o., 50012 Hradec Králové, Czech Republic
| | - David Stepek
- Internal Department, Military Hospital Brno, 61500 Brno, Czech Republic
| | - Ferdinando D'Amico
- Department of Gastroenterology and Digestive Endoscopy, San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Rachel West
- Department of Gastroenterology and Hepatology, Franciscus Gasthuis & Vlietland, 3045 PM Rotterdam, The Netherlands
| | - Lennard P L Gilissen
- Department of Gastroenterology and Hepatology, Catharina Hospital Eindhoven, 5623 EJ Eindhoven, The Netherlands
| | | | - Piotr Drobinski
- Centrum Medyczne Lukamed in Chojnice, 89-600 Chojnice, Poland
| | - Grzegorz Fronik
- Melita Medical-Centrum Proktologii, Onkologii i Chorób Jelit, 50-449 Wrocław, Poland
| | - Mirosław Fic
- Polish Society of Gastroenterology, 58-521 Jezów Sudecki, Poland
| | - Michał Walczak
- Institute of Human Genetics, Polish Academy of Sciences, 61-772 Poznan, Poland
| | - Maciej Kowalski
- Department of Gastroenterology, Centrum Diagnostyczno-Lecznicze Barska, 87-806 Włocławek, Poland
| | - Bartosz Korczowski
- Institute of Medical Sciences, Medical College, University of Rzeszów, 35-310 Rzeszów, Poland
| | - Michal Wiatr
- Ośrodek Badań Klinicznych CLINSANTE S.C. Ewa Galczak-Nowak Małgorzata Trzaska, Chałubińskiego, 85-004 Bydgoszcz, Poland
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, 54000 Vandoeuvre-lès-Nancy, France
- Department of Gastroenterology, Nancy University Hospital, 54500 Vandœuvre-lès-Nancy, France
- INFINY Institute, Nancy University Hospital, 54500 Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, 54500 Vandœuvre-lès-Nancy, France
- Groupe Hospitalier Privé Ambroise Paré-Hartmann, Paris IBD Center, 92200 Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
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Sävilammi T, Alakangas RR, Häyrynen T, Uusi-Heikkilä S. Gut Microbiota Profiling as a Promising Tool to Detect Equine Inflammatory Bowel Disease (IBD). Animals (Basel) 2024; 14:2396. [PMID: 39199930 PMCID: PMC11350833 DOI: 10.3390/ani14162396] [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: 06/28/2024] [Revised: 08/06/2024] [Accepted: 08/08/2024] [Indexed: 09/01/2024] Open
Abstract
Gastrointestinal disorders are common and debilitating in horses, but their diagnosis is often difficult and invasive. Fecal samples offer a non-invasive alternative to assessing the gastrointestinal health of horses by providing information about the gut microbiota and inflammation. In this study, we used 16S sequencing to compare the fecal bacterial diversity and composition of 27 healthy horses and 49 horses diagnosed with inflammatory bowel disease (IBD). We also measured fecal calprotectin concentration, a marker of intestinal inflammation, in healthy horses and horses with IBD. We found that microbiota composition differed between healthy horses and horses with IBD, although less than five percent of the variation in microbiota composition was explained by individual health status and age. Several differentially abundant bacterial taxa associated with IBD, age, or body condition were depleted from the most dominant Firmicutes phylum and enriched with the Bacteroidota phylum. An artificial neural network model predicted the probability of IBD among the test samples with 100% accuracy. Our study is the first to demonstrate the association between gut microbiota composition and chronic forms of IBD in horses and highlights the potential of using fecal samples as a non-invasive source of biomarkers for equine IBD.
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Affiliation(s)
- Tiina Sävilammi
- Department of Biological and Environmental Science, University of Jyväskylä, P.O. Box 35, 40014 Jyväskylä, Finland; (T.S.); (R.-R.A.)
- Department of Biology, University of Turku, 20014 Turku, Finland
| | - Rinna-Riikka Alakangas
- Department of Biological and Environmental Science, University of Jyväskylä, P.O. Box 35, 40014 Jyväskylä, Finland; (T.S.); (R.-R.A.)
| | - Tuomas Häyrynen
- Laukaa Horse Hospital, Ravitie 4, 41330 Vihtavuori, Finland;
| | - Silva Uusi-Heikkilä
- Department of Biological and Environmental Science, University of Jyväskylä, P.O. Box 35, 40014 Jyväskylä, Finland; (T.S.); (R.-R.A.)
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Qin X. Antibacterial Agents May Have Shifted Impacts on Inflammatory Bowel Diseases Along with Decrease in Gut Bacteria. Inflamm Bowel Dis 2024; 30:1228-1231. [PMID: 38457489 DOI: 10.1093/ibd/izae043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Indexed: 03/10/2024]
Abstract
Lay Summary
This article discussed the likely bell-shaped complicated impacts of antibacterial agents such as food additives like some artificial sweeteners on inflammatory bowel diseases including ulcerative colitis and Crohn’s disease along with decrease in gut bacteria.
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Affiliation(s)
- Xiaofa Qin
- GI Biopharam Inc, 918 Willow Grove Road, Westfield, NJ 07090, USA
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8
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Whelan K, Bancil AS, Lindsay JO, Chassaing B. Ultra-processed foods and food additives in gut health and disease. Nat Rev Gastroenterol Hepatol 2024; 21:406-427. [PMID: 38388570 DOI: 10.1038/s41575-024-00893-5] [Citation(s) in RCA: 52] [Impact Index Per Article: 52.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/05/2024] [Indexed: 02/24/2024]
Abstract
Ultra-processed foods (UPFs) and food additives have become ubiquitous components of the modern human diet. There is increasing evidence of an association between diets rich in UPFs and gut disease, including inflammatory bowel disease, colorectal cancer and irritable bowel syndrome. Food additives are added to many UPFs and have themselves been shown to affect gut health. For example, evidence shows that some emulsifiers, sweeteners, colours, and microparticles and nanoparticles have effects on a range of outcomes, including the gut microbiome, intestinal permeability and intestinal inflammation. Broadly speaking, evidence for the effect of UPFs on gut disease comes from observational epidemiological studies, whereas, by contrast, evidence for the effect of food additives comes largely from preclinical studies conducted in vitro or in animal models. Fewer studies have investigated the effect of UPFs or food additives on gut health and disease in human intervention studies. Hence, the aim of this article is to critically review the evidence for the effects of UPF and food additives on gut health and disease and to discuss the clinical application of these findings.
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Affiliation(s)
- Kevin Whelan
- Department of Nutritional Sciences, King's College London, London, UK.
| | - Aaron S Bancil
- Department of Nutritional Sciences, King's College London, London, UK
| | - James O Lindsay
- Blizard Institute, Queen Mary University of London, Barts and the London School of Medicine, London, UK
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9
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Jain S, Safo SE. DeepIDA-GRU: a deep learning pipeline for integrative discriminant analysis of cross-sectional and longitudinal multiview data with applications to inflammatory bowel disease classification. Brief Bioinform 2024; 25:bbae339. [PMID: 39007595 PMCID: PMC11771283 DOI: 10.1093/bib/bbae339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 02/29/2024] [Accepted: 06/28/2024] [Indexed: 07/16/2024] Open
Abstract
Biomedical research now commonly integrates diverse data types or views from the same individuals to better understand the pathobiology of complex diseases, but the challenge lies in meaningfully integrating these diverse views. Existing methods often require the same type of data from all views (cross-sectional data only or longitudinal data only) or do not consider any class outcome in the integration method, which presents limitations. To overcome these limitations, we have developed a pipeline that harnesses the power of statistical and deep learning methods to integrate cross-sectional and longitudinal data from multiple sources. In addition, it identifies key variables that contribute to the association between views and the separation between classes, providing deeper biological insights. This pipeline includes variable selection/ranking using linear and nonlinear methods, feature extraction using functional principal component analysis and Euler characteristics, and joint integration and classification using dense feed-forward networks for cross-sectional data and recurrent neural networks for longitudinal data. We applied this pipeline to cross-sectional and longitudinal multiomics data (metagenomics, transcriptomics and metabolomics) from an inflammatory bowel disease (IBD) study and identified microbial pathways, metabolites and genes that discriminate by IBD status, providing information on the etiology of IBD. We conducted simulations to compare the two feature extraction methods.
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Affiliation(s)
- Sarthak Jain
- Department of Electrical Engineering, University of
Minnesota, Minneapolis, MN 55455, United States
| | - Sandra E Safo
- Division of Biostatistics and Health Data Science, University of
Minnesota, Minneapolis, MN 55455, United States
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10
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Harwansh RK, Chauhan S, Deshmukh R, Mazumder R. Recent Insight into Herbal Bioactives-based Novel Approaches for Chronic Intestinal Inflammatory Disorders Therapy. Curr Pharm Biotechnol 2024; 25:1835-1857. [PMID: 38310453 DOI: 10.2174/0113892010282432231222060355] [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: 09/27/2023] [Revised: 12/12/2023] [Accepted: 12/15/2023] [Indexed: 02/05/2024]
Abstract
Inflammatory bowel disease (IBD) is a life-threatening complex disease. It causes chronic intestinal inflammation in GIT. IBD significantly affects people's lifestyles and carries a high risk of colon cancer. IBD involves the rectum, ileum, and colon, with clinical manifestations of bloody stools, weight loss, diarrhea, and abdominal pain. The prevalence of inflammatory disease is increasing dramatically worldwide. Over 16 million people are affected annually in India, with an economic burden of $6.8- $8.8 billion for treatment. Modern medicine can manage IBD as immunosuppressive agents, corticosteroids, tumor necrosis factor antagonists, integrin blockers, and amino-salicylates. However, these approaches are allied with limitations such as limited efficacy, drug resistance, undesired side effects, and overall cost, which cannot be ignored. Hence, the herbal bioactives derived from various plant resources can be employed in managing IBD. Science Direct, PubMed, Google, and Scopus databases have been searched for conclusively relevant herbal plant-based anti-inflammatory agent compositions. Studies were screened through analysis of previously published review articles. Eminent herbal bioactives, namely curcumin, resveratrol, ellagic acid, silybin, catechin, kaempferol, icariin, glycyrrhizin acid, berberine, quercetin, rutin, and thymol are reported to be effective against IBD. Herbal leads are promising treatment options for IBD; they have been shown to display antiinflammatory and antioxidant properties by targeting enzymes and regulating the expressions of various inflammatory mediators. Natural products have been reported to have anti-inflammatory properties in various clinical and preclinical studies, and some are available as herbal preparations. Herbal medicine would be promising in association with the implication of a novel drug delivery system for managing IBD.
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Affiliation(s)
- Ranjit K Harwansh
- Institute of Pharmaceutical Research, GLA University, Mathura, 281406, India
| | - Sonia Chauhan
- Institute of Pharmaceutical Research, GLA University, Mathura, 281406, India
- NIET Pharmacy Institute, Greater Noida, 201310, India
| | - Rohitas Deshmukh
- Institute of Pharmaceutical Research, GLA University, Mathura, 281406, India
| | - Rupa Mazumder
- NIET Pharmacy Institute, Greater Noida, 201310, India
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Jia Z, Wang Y, Li S, Yang M, Liu Z, Zhang H. MICDnet: Multimodal information processing networks for Crohn's disease diagnosis. Comput Biol Med 2024; 168:107790. [PMID: 38042104 DOI: 10.1016/j.compbiomed.2023.107790] [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: 09/04/2023] [Revised: 11/22/2023] [Accepted: 11/28/2023] [Indexed: 12/04/2023]
Abstract
Crohn's disease (CD) is a chronic inflammatory disease with increasing incidence worldwide and unclear etiology. Its clinical manifestations vary depending on location, extent, and severity of the lesions. In order to diagnose Crohn's disease, medical professionals need to comprehensively analyze patients' multimodal examination data, which includes medical imaging such as colonoscopy, pathological, and text information from clinical records. The processes of multimodal data analysis require collaboration among medical professionals from different departments, which wastes a lot of time and human resources. Therefore, a multimodal medical assisted diagnosis system for Crohn's disease is particularly significant. Existing network frameworks find it hard to effectively capture multimodal patient data for diagnosis, and multimodal data for Crohn's disease is currently lacking. In addition,a combination of data from patients with similar symptoms could serve as an effective reference for disease diagnosis. Thus, we propose a multimodal information diagnosis network (MICDnet) to learn CD feature representations by integrating colonoscopy, pathology images and clinical texts. Specifically, MICDnet first preprocesses each modality data, then uses encoders to extract image and text features separately. After that, multimodal feature fusion is performed. Finally, CD classification and diagnosis are conducted based on the fused features. Under the authorization, we build a dataset of 136 hospitalized inspectors, with colonoscopy images of seven areas, pathology images, and clinical record text for each individual. Training MICDnet on this dataset shows that multimodal diagnosis can improve the diagnostic accuracy of CD, and the diagnostic performance of MICDnet is superior to other models.
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Affiliation(s)
- Zixi Jia
- Faculty of Robot Science and Engineering, Northeastern University, Shenyang, Liaoning, 110169, China
| | - Yilu Wang
- Faculty of Robot Science and Engineering, Northeastern University, Shenyang, Liaoning, 110169, China
| | - Shengming Li
- Faculty of Robot Science and Engineering, Northeastern University, Shenyang, Liaoning, 110169, China
| | - Meiqi Yang
- Department of Endoscopy, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, China
| | - Zhongyuan Liu
- Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China.
| | - Huijing Zhang
- Department of Endoscopy, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, China.
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Posta E, Fekete I, Gyarmati E, Stündl L, Zold E, Barta Z. The Effects of Artificial Sweeteners on Intestinal Nutrient-Sensing Receptors: Dr. Jekyll or Mr. Hyde? Life (Basel) 2023; 14:10. [PMID: 38276259 PMCID: PMC10817473 DOI: 10.3390/life14010010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 12/14/2023] [Accepted: 12/15/2023] [Indexed: 01/27/2024] Open
Abstract
The consumption of artificial and low-calorie sweeteners (ASs, LCSs) is an important component of the Western diet. ASs play a role in the pathogenesis of metabolic syndrome, dysbiosis, inflammatory bowel diseases (IBDs), and various inflammatory conditions. Intestinal nutrient-sensing receptors act as a crosstalk between dietary components, the gut microbiota, and the regulation of immune, endocrinological, and neurological responses. This narrative review aimed to summarize the possible effects of ASs and LCSs on intestinal nutrient-sensing receptors and their related functions. Based on the findings of various studies, long-term AS consumption has effects on the gut microbiota and intestinal nutrient-sensing receptors in modulating incretin hormones, antimicrobial peptides, and cytokine secretion. These effects contribute to the regulation of glucose metabolism, ion transport, gut permeability, and inflammation and modulate the gut-brain, and gut-kidney axes. Based on the conflicting findings of several in vitro, in vivo, and randomized and controlled studies, artificial sweeteners may have a role in the pathogenesis of IBDs, functional bowel diseases, metabolic syndrome, and cancers via the modulation of nutrient-sensing receptors. Further studies are needed to explore the exact mechanisms underlying their effects to decide the risk/benefit ratio of sugar intake reduction via AS and LCS consumption.
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Affiliation(s)
- Edit Posta
- GI Unit, Department of Infectology, Faculty of Medicine, University of Debrecen, Bartok Bela Street 2-26, 4031 Debrecen, Hungary; (E.G.); (Z.B.)
| | - Istvan Fekete
- Institute of Food Technology, Faculty of Agricultural and Food Sciences and Environmental Management, University of Debrecen, Böszörményi út 138, 4032 Debrecen, Hungary; (I.F.); (L.S.)
| | - Eva Gyarmati
- GI Unit, Department of Infectology, Faculty of Medicine, University of Debrecen, Bartok Bela Street 2-26, 4031 Debrecen, Hungary; (E.G.); (Z.B.)
- Doctoral School of Clinical Immunology and Allergology, Faculty of Medicine, University of Debrecen, Nagyerdei Blvd. 98, 4032 Debrecen, Hungary
| | - László Stündl
- Institute of Food Technology, Faculty of Agricultural and Food Sciences and Environmental Management, University of Debrecen, Böszörményi út 138, 4032 Debrecen, Hungary; (I.F.); (L.S.)
| | - Eva Zold
- Department of Clinical Immunology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, Móricz Zsigmond Str. 22, 4032 Debrecen, Hungary;
| | - Zsolt Barta
- GI Unit, Department of Infectology, Faculty of Medicine, University of Debrecen, Bartok Bela Street 2-26, 4031 Debrecen, Hungary; (E.G.); (Z.B.)
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Pasternak G, Chrzanowski G, Aebisher D, Myśliwiec A, Dynarowicz K, Bartusik-Aebisher D, Sosna B, Cieślar G, Kawczyk-Krupka A, Filip R. Crohn's Disease: Basic Characteristics of the Disease, Diagnostic Methods, the Role of Biomarkers, and Analysis of Metalloproteinases: A Review. Life (Basel) 2023; 13:2062. [PMID: 37895443 PMCID: PMC10608618 DOI: 10.3390/life13102062] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 10/10/2023] [Accepted: 10/12/2023] [Indexed: 10/29/2023] Open
Abstract
Crohn's disease is a chronic inflammatory bowel disease that affects the ileum and/or large intestine. At the same time, it can also affect any other part of the human body, i.e., from the mouth to the anus. In Crohn's disease, the physiology and functioning of the epithelial barrier are inhibited due to the correlation of various factors, such as the environment, genetic susceptibility or intestinal microbiota. The symptoms are very troublesome and cause a significant reduction in quality of life, sometimes occurring with paralyzing permanent damage to the digestive tract, requiring enteral or parenteral nutrition throughout life. In order to make a proper and accurate diagnosis, an appropriately selected diagnostic path in a given clinical entity is necessary. Standard diagnostic methods are: laboratory examination, histopathological examination, endoscopic examination, X-ray, computed tomography, ultrasound examination and magnetic resonance imaging. Medical biology and the analysis of metalloproteinases have also proved helpful in diagnosing changes occurring as a result of Crohn's disease. Here we provide a thorough review of the latest reports on Crohn's disease and its genetic conditions, symptoms, morphology, diagnosis (including the analysis of Crohn's disease biomarkers, i.e., metalloproteinases) and treatment.
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Affiliation(s)
- Grzegorz Pasternak
- Department of General Surgery, Provincial Clinical Hospital No. 2 in Rzeszów, 35-301 Rzeszów, Poland;
| | - Grzegorz Chrzanowski
- Department of Biology, College of Natural Sciences, University of Rzeszów, 35-310 Rzeszów, Poland
| | - David Aebisher
- Department of Photomedicine and Physical Chemistry, Medical College, University of Rzeszów, 35-310 Rzeszów, Poland
| | - Angelika Myśliwiec
- Center for Innovative Research in Medical and Natural Sciences, Medical College, University of Rzeszów, 35-310 Rzeszów, Poland; (A.M.); (K.D.)
| | - Klaudia Dynarowicz
- Center for Innovative Research in Medical and Natural Sciences, Medical College, University of Rzeszów, 35-310 Rzeszów, Poland; (A.M.); (K.D.)
| | - Dorota Bartusik-Aebisher
- Department of Biochemistry and General Chemistry, Medical College, University of Rzeszów, 35-310 Rzeszów, Poland;
| | - Barbara Sosna
- Department of Internal Medicine, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia in Katowice, Batorego 15 Street, 41-902 Bytom, Poland; (B.S.); (G.C.); (A.K.-K.)
| | - Grzegorz Cieślar
- Department of Internal Medicine, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia in Katowice, Batorego 15 Street, 41-902 Bytom, Poland; (B.S.); (G.C.); (A.K.-K.)
| | - Aleksandra Kawczyk-Krupka
- Department of Internal Medicine, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia in Katowice, Batorego 15 Street, 41-902 Bytom, Poland; (B.S.); (G.C.); (A.K.-K.)
| | - Rafał Filip
- Department of Internal Medicine, Medical College, University of Rzeszów, 35-310 Rzeszów, Poland;
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Swastha D, Varsha N, Aravind S, Samyuktha KB, Yokesh MM, Balde A, Ayilya BL, Benjakul S, Kim SK, Nazeer RA. Alginate-based drug carrier systems to target inflammatory bowel disease: A review. Int J Biol Macromol 2023:125472. [PMID: 37336375 DOI: 10.1016/j.ijbiomac.2023.125472] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Revised: 06/06/2023] [Accepted: 06/16/2023] [Indexed: 06/21/2023]
Abstract
Inflammatory bowel disease (IBD) is an inflammatory disorder that affects the gastrointestinal tract. IBD has become an increasingly common condition in both developed and developing nations over the last few decades, owing to a variety of factors like a rising population and diets packed with processed and junk foods. While the root pathophysiology of IBD is unknown, treatments are focused on medications aimed to mitigate symptoms. Alginate (AG), a marine-derived polysaccharide, is extensively studied for its biocompatibility, pH sensitivity, and crosslinking nature. This polymer is thoroughly researched in drug delivery systems for IBD treatment, as it is naturally available, non-toxic, cost effective, and can be easily and safely cross-linked with other polymers to form an interconnected network, which helps in controlling the release of drugs over an extended period. There are various types of drug delivery systems developed from AG to deliver therapeutic agents; among them, nanotechnology-based systems and hydrogels are popular due to their ability to facilitate targeted drug delivery, reduce dosage, and increase the therapeutic efficiency. AG-based carrier systems are not only used for the sustained release of drug, but also used in the delivery of siRNA, interleukins, and stem cells for site directed drug delivery and tissue regenerating ability respectively. This review is focussed on pathogenesis and currently studied medications for IBD, AG-based drug delivery systems and their properties for the alleviation of IBD. Moreover, future challenges are also be discoursed to improve the research of AG in the field of biopharmaceuticals and drug delivery.
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Affiliation(s)
- Dinakar Swastha
- Biopharmaceuticals Lab, Department of Biotechnology, School of Bioengineering, SRMInstitute of Science and Technology, Kattankulathur, Chennai, 603203, Tamilnadu, India
| | - Nambolan Varsha
- Biopharmaceuticals Lab, Department of Biotechnology, School of Bioengineering, SRMInstitute of Science and Technology, Kattankulathur, Chennai, 603203, Tamilnadu, India
| | - Suresh Aravind
- Biopharmaceuticals Lab, Department of Biotechnology, School of Bioengineering, SRMInstitute of Science and Technology, Kattankulathur, Chennai, 603203, Tamilnadu, India
| | - Kavassery Balasubramanian Samyuktha
- Biopharmaceuticals Lab, Department of Biotechnology, School of Bioengineering, SRMInstitute of Science and Technology, Kattankulathur, Chennai, 603203, Tamilnadu, India
| | - Muruganandam Mohaneswari Yokesh
- Biopharmaceuticals Lab, Department of Biotechnology, School of Bioengineering, SRMInstitute of Science and Technology, Kattankulathur, Chennai, 603203, Tamilnadu, India
| | - Akshad Balde
- Biopharmaceuticals Lab, Department of Biotechnology, School of Bioengineering, SRMInstitute of Science and Technology, Kattankulathur, Chennai, 603203, Tamilnadu, India
| | - Bakthavatchalam Loganathan Ayilya
- Biopharmaceuticals Lab, Department of Biotechnology, School of Bioengineering, SRMInstitute of Science and Technology, Kattankulathur, Chennai, 603203, Tamilnadu, India
| | - Soottawat Benjakul
- Department of Food Technology, Faculty of Agro-Industry, Prince of Songkhla University, 90112 Hat Yai, Songkhla, Thailand
| | - Se-Kwon Kim
- Department of Marine Science and Convergence Engineering, Hanyang University, Ansan, 11558, Gyeonggi-do, South Korea
| | - Rasool Abdul Nazeer
- Biopharmaceuticals Lab, Department of Biotechnology, School of Bioengineering, SRMInstitute of Science and Technology, Kattankulathur, Chennai, 603203, Tamilnadu, India.
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Cortesi PA, Fiorino G, Peyrin-Biroulet L, Mantovani LG, Jairath V, Paridaens K, Andersson FL, Danese S. Non-invasive monitoring and treat-to-target approach are cost-effective in patients with mild-moderate ulcerative colitis. Aliment Pharmacol Ther 2023; 57:486-495. [PMID: 36377366 DOI: 10.1111/apt.17261] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 09/07/2022] [Accepted: 10/09/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND There are no data to assess the value associated with a treat-to-target (T2T) strategy based on tight control of mild-moderate ulcerative colitis (UC). AIM To assess the cost-effectiveness of a T2T approach based on the normalisation of clinical signs and faecal calprotectin (FC) METHODS: A decision analytical Markov model was developed to compare T2T algorithm combining clinical symptoms and FC levels to define treatment response and the possible switch to the next treatment line (T2T-FC), and the reference strategy based only on symptoms. The model included five treatment lines and was conducted from the Italian national health service (NHS) perspective using a 3-year time horizon. The model calculated the incremental cost-effectiveness ratio as € per relapse avoided. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS The cost-effectiveness analysis produced an increased time spent by a patient in clinical remission and FC ≤ 100 level (+0.177 years; about 2 months) and a decreasing number of relapses (-0.1937; -20.9%) per patient using a T2T-FC approach compared to only symptoms. Furthermore, the T2T-FC was associated with higher cost (+€1795). The ICER estimated was €9263 per relapse avoided. These results were confirmed by sensitivity analyses. CONCLUSIONS T2T-FC approach resulted in a higher benefit for mild-moderate UC patients in terms of time in remission and incidence of relapse but was associated with higher costs. Clinical trials and real-world clinical studies are needed to provide additional data on the cost-benefit of this approach.
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Affiliation(s)
- Paolo Angelo Cortesi
- Research Centre on Public Health (CESP), University of Milano-Bicocca, Monza, Italy
| | - Gionata Fiorino
- Department of Gastroenterology and Digestive Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Lorenzo Giovanni Mantovani
- Research Centre on Public Health (CESP), University of Milano-Bicocca, Monza, Italy.,IRCCS, Istituto Auxologico Italiano, Milan, Italy
| | - Vipul Jairath
- Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada
| | | | - Fredrik L Andersson
- Ferring Pharmaceuticals A/S - International PharmaScience Center, Kastrup, Denmark
| | - Silvio Danese
- Department of Gastroenterology and Digestive Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy
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16
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Lee SH, Seo D, Lee KH, Park SJ, Park S, Kim H, Kim T, Joo IH, Park JM, Kang YH, Lim GH, Kim DH, Yang JY. Biometabolites of Citrus unshiu Peel Enhance Intestinal Permeability and Alter Gut Commensal Bacteria. Nutrients 2023; 15:nu15020319. [PMID: 36678190 PMCID: PMC9862503 DOI: 10.3390/nu15020319] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/02/2023] [Accepted: 01/06/2023] [Indexed: 01/11/2023] Open
Abstract
Flavanones in Citrus unshiu peel (CUP) have been used as therapeutic agents to reduce intestinal inflammation; however, the anti-inflammatory effects of their biometabolites remain ambiguous. Here, we identified aglycone-type flavanones, such as hesperetin and naringenin, which were more abundant in the bioconversion of the CUP than in the ethanol extracts of the CUP. We found that the bioconversion of the CUP induced the canonical nuclear factor-κB pathway via degradation of IκB in Caco-2 cells. To check the immune suppressive capacity of the aglycones of the CUP in vivo, we orally administered the bioconversion of the CUP (500 mg/kg) to mice for two weeks prior to the 3% dextran sulfate sodium treatment. The CUP-pretreated group showed improved body weight loss, colon length shortage, and intestinal inflammation than the control mice. We also found a significant decrease in the population of lamina propria Th17 cells in the CUP-pretreated group following dextran sodium sulfate (DSS) treatment and an increase in mRNA levels of occludin in CUP-treated Caco-2 cells. Pyrosequencing analysis revealed a decreased abundance of Alistipes putredinis and an increased abundance of Muribaculum intestinale in the feces of the CUP-pretreated mice compared to those of the control mice. Overall, these findings suggest that the pre-administration of CUP biometabolites may inhibit the development of murine colitis by modulating intestinal permeability and the gut microbiome.
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Affiliation(s)
- Se-Hui Lee
- Department of Integrated Biological Science, Pusan National University, Busan 46241, Republic of Korea
| | - Dongju Seo
- Department of Integrated Biological Science, Pusan National University, Busan 46241, Republic of Korea
| | - Kang-Hee Lee
- Department of Integrated Biological Science, Pusan National University, Busan 46241, Republic of Korea
| | - So-Jung Park
- Department of Integrated Biological Science, Pusan National University, Busan 46241, Republic of Korea
| | - Sun Park
- Department of Integrated Biological Science, Pusan National University, Busan 46241, Republic of Korea
| | - Hyeyun Kim
- Department of Integrated Biological Science, Pusan National University, Busan 46241, Republic of Korea
| | - Taekyung Kim
- Department of Biology Education, Pusan National University, Busan 46241, Republic of Korea
| | - In Hwan Joo
- Department of Pathology, College of Korean Medicine, Daejeon University, Daejeon 34520, Republic of Korea
| | - Jong-Min Park
- Department of Pathology, College of Korean Medicine, Daejeon University, Daejeon 34520, Republic of Korea
| | - Yun-Hwan Kang
- Department of Industry Promotion, National Institute for Korean Medicine Development, Geongsan 38540, Republic of Korea
| | - Gah-Hyun Lim
- Department of Biological Sciences, Pusan National University, Busan 46241, Republic of Korea
| | - Dong Hee Kim
- Department of Pathology, College of Korean Medicine, Daejeon University, Daejeon 34520, Republic of Korea
| | - Jin-Young Yang
- Department of Integrated Biological Science, Pusan National University, Busan 46241, Republic of Korea
- Department of Biological Sciences, Pusan National University, Busan 46241, Republic of Korea
- Correspondence: ; Tel.: +82-51-510-2286; Fax: +82-51-581-2962
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Lee HL, Kim JM, Moon JH, Kim MJ, Jeong HR, Go MJ, Kim HJ, Eo HJ, Lee U, Heo HJ. Anti-Amnesic Effect of Synbiotic Supplementation Containing Corni fructus and Limosilactobacillus reuteri in DSS-Induced Colitis Mice. Int J Mol Sci 2022; 24:ijms24010090. [PMID: 36613533 PMCID: PMC9820465 DOI: 10.3390/ijms24010090] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 12/12/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
This study was conducted to compare the synbiotic activity between Corni fructus (C. fructus) and Limosilactobacillus reuteri (L. reuteri) on dextran sulfate sodium (DSS)-induced colitis and cognitive dysfunction in C57BL/6 mice. C. fructus (as prebiotics, PRE), L. reuteri (as probiotics, PRO), and synbiotics (as a mixture of L. reuteri and C. fructus, SYN) were fed to mice for 3 weeks. Consumption of PRE, PRO, and SYN ameliorated colitis symptoms in body weight, large intestinal length, and serum albumin level. Moreover, SYN showed a synergistic effect on intestinal permeability and intestinal anti-inflammation response. Also, SYN significantly improved cognitive function as a result of measuring the Y-maze and passive avoidance tests in DSS-induced behavioral disorder mice. Especially, SYN also restored memory function by increasing the cholinergic system and reducing tau and amyloid β pathology. In addition, PRE, PRO, and SYN ameliorated dysbiosis by regulating the gut microbiota and the concentration of short-chain fatty acids (SCFAs) in feces. The bioactive compounds of C. fructus were identified with quinic acid, morroniside, loganin, and cornuside, using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS2). In conclusion, synbiotic supplementation alleviated DSS-induced colitis and cognitive dysfunction by modulating gut microbiota, proinflammatory cytokines, and SCFAs production.
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Affiliation(s)
- Hyo Lim Lee
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea
| | - Jong Min Kim
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea
| | - Jong Hyun Moon
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea
| | - Min Ji Kim
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea
| | - Hye Rin Jeong
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea
| | - Min Ji Go
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea
| | - Hyun-Jin Kim
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea
| | - Hyun Ji Eo
- Division of Special Forest Resources, Department of Forest Bioresources, National Institute of Forest Science (NIFoS), Suwon 16631, Republic of Korea
| | - Uk Lee
- Division of Special Forest Resources, Department of Forest Bioresources, National Institute of Forest Science (NIFoS), Suwon 16631, Republic of Korea
| | - Ho Jin Heo
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea
- Correspondence: ; Tel.: +82-(55)-7721907
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18
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Fu T, Wang X, Chen J. Editorial: investigating the association between sweetened beverages and risk of inflammatory bowel disease-authors' reply. Aliment Pharmacol Ther 2022; 56:1088-1089. [PMID: 35995740 DOI: 10.1111/apt.17187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Tian Fu
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Xiaoyan Wang
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Jie Chen
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, China.,Centre for Global Health, Zhejiang University, Hangzhou, China
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19
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Hubrecht I, Baenas N, Sina C, Wagner AE. Effects of non‐caloric artificial sweeteners on naïve and dextran sodium sulfate‐exposed
Drosophila melanogaster. FOOD FRONTIERS 2022. [DOI: 10.1002/fft2.147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Affiliation(s)
- Inga Hubrecht
- Institute of Nutritional Medicine Campus Lübeck University Hospital Schleswig‐Holstein Lübeck Germany
| | - Nieves Baenas
- Institute of Nutritional Medicine Campus Lübeck University Hospital Schleswig‐Holstein Lübeck Germany
- Department of Food Technology, Food Science and Nutrition, Faculty of Veterinary Sciences, University of Murcia, Campus de Espinardo, 30100, Murcia, Spain
| | - Christian Sina
- Institute of Nutritional Medicine Campus Lübeck University Hospital Schleswig‐Holstein Lübeck Germany
| | - Anika E. Wagner
- Institute of Nutritional Sciences Justus‐Liebig‐University Giessen Germany
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20
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Jarmakiewicz-Czaja S, Piątek D, Filip R. The impact of selected food additives on the gastrointestinal tract in the example of nonspecific inflammatory bowel diseases. Arch Med Sci 2022; 18:1286-1296. [PMID: 36160334 PMCID: PMC9479712 DOI: 10.5114/aoms/125001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 07/06/2020] [Indexed: 11/17/2022] Open
Abstract
Various types of food additives are widely used in the food industry. Due to their properties extending the usefulness for consuming food products, they give them different colours, consistency, or taste. The products are marked 'E' and the code is assigned to the subscription used. Many of the supplements affect human health negatively. Emulsifiers or stabilizers can lead to epithelial loads and the development of inflammation. Sucrose and other sweeteners may change the composition of the intestinal microflora and thus lead to intestinal blockage. Some additives classified as preservatives are available and may predispose to intestinal dysbiosis. Available substances belonging to food dyes may predispose to genotoxic and cytotoxic effects and cause inflammation in the intestines. Substances added to food can also cause disorders of intestinal homeostasis.
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Affiliation(s)
| | - Dominika Piątek
- Department of Conservative Dentistry with Endodontics, Medical University of Lublin, Lublin, Poland
| | - Rafał Filip
- Department of Gastroenterology with IBD, Unit of Clinical Hospital 2, Rzeszow, Poland
- Medical College of Rzeszow University, Rzeszow, Poland
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21
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Guo M, Liu X, Tan Y, Kang F, Zhu X, Fan X, Wang C, Wang R, Liu Y, Qin X, Jiang M, Wang X. Sucralose enhances the susceptibility to dextran sulfate sodium (DSS) induced colitis in mice with changes in gut microbiota. Food Funct 2021; 12:9380-9390. [PMID: 34606537 DOI: 10.1039/d1fo01351c] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Sucralose is one of the most widely used artificial sweeteners, free of nutrients and calories. Its approval and uses correlate with many of the worldwide epidemiological changes in inflammatory bowel disease (IBD). Multiple animal studies by us and others showed that sucralose exacerbated ileitis in SAMP1/YitFc mice and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. In this study, we further investigated the effect of sucralose on dextran sulfate sodium (DSS)-induced colitis in mice and the associated mechanisms. Male C57BL/6 mice received 1.5 mg ml-1 sucralose in drinking water for 6 weeks. Then, 2.5% DSS was added to drinking water for 7 days to induce ulcerative colitis (UC). The results showed that, compared with the DSS group, administration of sucralose exacerbated the severity of colitis as indicated by the further decrease in body weight, increase in disease activity index (DAI) and the expression of pro-inflammatory cytokines, as well as the activation of the TLR5-MyD88-NF-κB signaling pathway, and the disturbances of intestinal barrier function, along with changes in the intestinal microbiota. Our findings indicate that sucralose may increase the susceptibility to DSS-induced colitis through causing dysbiosis of intestinal microbiota and damage to the intestinal barrier.
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Affiliation(s)
- Mengru Guo
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, 150000, China.
| | - Xinran Liu
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, 150000, China.
| | - Yiwei Tan
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, 150000, China.
| | - Fangyuan Kang
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, 150000, China.
| | - Xinghua Zhu
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, 150000, China.
| | - Xingguo Fan
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, 150000, China.
| | - Chenxi Wang
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, 150000, China.
| | - Rui Wang
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, 150000, China.
| | - Yuanli Liu
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, 150000, China.
| | | | - Mingshan Jiang
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xiuhong Wang
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, 150000, China.
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22
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Byrne LW, McKay D. Does perioperative biological therapy increase 30-day post-operative complication rates in inflammatory bowel disease patients undergoing intra-abdominal surgery? A systematic review. Surgeon 2021; 19:e153-e167. [PMID: 34581275 DOI: 10.1016/j.surge.2020.09.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 06/29/2020] [Accepted: 09/06/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Biopharmaceuticals revolutionised inflammatory bowel disease (IBD) treatment. However, it is postulated they compromise immunity, collagen production and angiogenesis resulting in infective post-operative complications and altered wound/anastomotic healing. Research has failed to agree on risks associated with perioperative biologics therefore it was anticipated that a systematic review may provide a consensus and contribute recommendations for clinical practice. METHODS A systematic review conducted as per PRISMA guidelines included a methodical search of PubMed, Google Scholar, EMBASE/Ovid and Cochrane Library using MeSH and/or keywords for papers published between 01/01/1998 and 04/02/2019.The population analysed included adult ulcerative colitis, Crohn's disease, Indeterminate Colitis or IBD unclassified patients. The intervention was intra-abdominal surgery in patients treated with biological therapy in the preceding 12 weeks compared to patients who had intra-abdominal surgery without biological therapy within the defined timeframe. The primary outcome was surgical site infection (SSI) with secondary outcomes including wound dehiscence, intra-abdominal sepsis/abscess, systemic infection and anastomotic breakdown within 30 days post-procedure. Papers were evaluated by two independent reviewers and those included were assessed for quality/bias using the Newcastle-Ottowa scale. RESULTS 2064 UC, Crohn's and IC patients were analysed across 8 included studies. Several studies' multivariate analyses demonstrated corticosteroids to be independent predictors of morbidity. There are no increased complications associated with anti-TNFα exposure while vedolizumab increased SSI and small bowel obstruction. CONCLUSION Prospective studies and randomised control trials are required to clarify study outcomes and recommendations published to date. Presently, biologics should continue to be used and considered beneficial in this population.
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Affiliation(s)
| | - Damian McKay
- Craigavon Area Hospital, 68 Lurgan Rd, Portadown, Craigavon, BT63 5QQ, UK
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23
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Basson AR, Rodriguez-Palacios A, Cominelli F. Artificial Sweeteners: History and New Concepts on Inflammation. Front Nutr 2021; 8:746247. [PMID: 34631773 PMCID: PMC8497813 DOI: 10.3389/fnut.2021.746247] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 08/23/2021] [Indexed: 12/12/2022] Open
Abstract
Since the introduction of artificial sweeteners (AS) to the North American market in the 1950s, a growing number of epidemiological and animal studies have suggested that AS may induce changes in gut bacteria and gut wall immune reactivity, which could negatively affect individuals with or susceptible to chronic inflammatory conditions such as inflammatory bowel disease (IBD), a disorder that has been growing exponentially in westernized countries. This review summarizes the history of current FDA-approved AS and their chemical composition, metabolism, and bacterial utilization, and provides a scoping overview of the disease mechanisms associated with the induction or prevention of inflammation in IBD. We provide a general outlook on areas that have been both largely and scarcely studied, emerging concepts using silica, and describe the effects of AS on acute and chronic forms of intestinal inflammation.
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Affiliation(s)
- Abigail Raffner Basson
- Division of Gastroenterology and Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, United States
- Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
| | - Alexander Rodriguez-Palacios
- Division of Gastroenterology and Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, United States
- Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
- Mouse Models, Silvio O'Conte Cleveland Digestive Diseases Research Core Center, Cleveland, OH, United States
- Germ-Free and Gut Microbiome Core, Digestive Health Research Institute, Case Western Reserve University, Cleveland, OH, United States
| | - Fabio Cominelli
- Division of Gastroenterology and Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, United States
- Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
- Mouse Models, Silvio O'Conte Cleveland Digestive Diseases Research Core Center, Cleveland, OH, United States
- Germ-Free and Gut Microbiome Core, Digestive Health Research Institute, Case Western Reserve University, Cleveland, OH, United States
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24
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Qin X. High Fecal Proteolytic Activity That Precedes Ulcerative Colitis Likely Results From Impaired Inactivation of Pancreatic Proteases Rather Than Bacteria. Inflamm Bowel Dis 2021; 27:e104. [PMID: 34125213 DOI: 10.1093/ibd/izab142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Xiaofa Qin
- GI Biopharma Inc., Westfield, New Jersey, USA
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25
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Ozaka S, Sonoda A, Ariki S, Kamiyama N, Hidano S, Sachi N, Ito K, Kudo Y, Minata M, Saechue B, Dewayani A, Chalalai T, Soga Y, Takahashi Y, Fukuda C, Mizukami K, Okumura R, Kayama H, Murakami K, Takeda K, Kobayashi T. Protease inhibitory activity of secretory leukocyte protease inhibitor ameliorates murine experimental colitis by protecting the intestinal epithelial barrier. Genes Cells 2021; 26:807-822. [PMID: 34379860 DOI: 10.1111/gtc.12888] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 08/04/2021] [Accepted: 08/07/2021] [Indexed: 12/13/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder in the intestine, and the dysfunction of intestinal epithelial barrier (IEB) may trigger the onset of IBD. Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor that has been implicated in the tissue-protective effect in the skin and lung. We found that SLPI was induced in lipopolysaccharides-treated colon carcinoma cell line and in the colon of dextran sulfate sodium (DSS)-treated mice. SLPI-deficient mice were administered DSS to induce colitis and sustained severe inflammation compared with wild-type mice. The colonic mucosa of SLPI-deficient mice showed more severe inflammation with neutrophil infiltration and higher levels of proinflammatory cytokines compared with control mice. Moreover, neutrophil elastase (NE) activity in SLPI-deficient mice was increased and IEB function was severely impaired in the colon, accompanied with the increased number of apoptotic cells. Importantly, we demonstrated that DSS-induced colitis was ameliorated by administration of protease inhibitor SSR69071 and recombinant SLPI. These results suggest that the protease inhibitory activity of SLPI protects from colitis by preventing IEB dysfunction caused by excessive NE activity, which provides insight into the novel function of SLPI in the regulation of gut homeostasis and therapeutic approaches for IBD.
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Affiliation(s)
- Sotaro Ozaka
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan.,Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Akira Sonoda
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan.,Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Shimpei Ariki
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan.,Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Naganori Kamiyama
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Shinya Hidano
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Nozomi Sachi
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kanako Ito
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Yoko Kudo
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Mizuki Minata
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Benjawan Saechue
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Astri Dewayani
- Department of Anatomy, Histology, and Pharmacology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Thanyakorn Chalalai
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Yasuhiro Soga
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Yuya Takahashi
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Chiaki Fukuda
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kazuhiro Mizukami
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan.,Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Ryu Okumura
- Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan
| | - Hisako Kayama
- Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan
| | - Kazunari Murakami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kiyoshi Takeda
- Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan
| | - Takashi Kobayashi
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
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26
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Bin Masud S, Jenkins C, Hussey E, Elkin-Frankston S, Mach P, Dhummakupt E, Aeron S. Utilizing machine learning with knockoff filtering to extract significant metabolites in Crohn's disease with a publicly available untargeted metabolomics dataset. PLoS One 2021; 16:e0255240. [PMID: 34324558 PMCID: PMC8320926 DOI: 10.1371/journal.pone.0255240] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 07/12/2021] [Indexed: 12/26/2022] Open
Abstract
Metabolomic data processing pipelines have been improving in recent years, allowing for greater feature extraction and identification. Lately, machine learning and robust statistical techniques to control false discoveries are being incorporated into metabolomic data analysis. In this paper, we introduce one such recently developed technique called aggregate knockoff filtering to untargeted metabolomic analysis. When applied to a publicly available dataset, aggregate knockoff filtering combined with typical p-value filtering improves the number of significantly changing metabolites by 25% when compared to conventional untargeted metabolomic data processing. By using this method, features that would normally not be extracted under standard processing would be brought to researchers' attention for further analysis.
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Affiliation(s)
- Shoaib Bin Masud
- Department of Electrical and Computer Engineering, Tufts University, Medford, MA, United States of America
| | - Conor Jenkins
- DEVCOM Chemical Biological Center, Aberdeen Proving Ground, Aberdeen, MD, United States of America
| | - Erika Hussey
- DEVCOM Soldier Center, Natick, MA, United States of America
| | | | - Phillip Mach
- DEVCOM Chemical Biological Center, Aberdeen Proving Ground, Aberdeen, MD, United States of America
| | - Elizabeth Dhummakupt
- DEVCOM Chemical Biological Center, Aberdeen Proving Ground, Aberdeen, MD, United States of America
| | - Shuchin Aeron
- Department of Electrical and Computer Engineering, Tufts University, Medford, MA, United States of America
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27
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Marques JG, Shokry E, Frivolt K, Werkstetter KJ, Brückner A, Schwerd T, Koletzko S, Koletzko B. Metabolomic Signatures in Pediatric Crohn's Disease Patients with Mild or Quiescent Disease Treated with Partial Enteral Nutrition: A Feasibility Study. SLAS Technol 2021; 26:165-177. [PMID: 33207993 PMCID: PMC7985853 DOI: 10.1177/2472630320969147] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 09/29/2020] [Accepted: 10/06/2020] [Indexed: 12/22/2022]
Abstract
Little is known about the metabolic response of pediatric Crohn's disease (CD) patients to partial enteral nutrition (PEN) therapy and the impact of disease activity and inflammation. We analyzed plasma samples from a nonrandomized controlled intervention study investigating the effect of partial enteral nutrition (PEN) on bone health and growth throughout one year with untargeted metabolomics using high-performance liquid chromatography (HPLC) coupled with high-resolution mass spectrometry (HRMS). Thirty-four paired samples from two time points (baseline and 12 months) were analyzed. Patients (median age: 13.9 years, range: 7-18.9 years, 44% females) were in remission or had mild disease activity. The intervention group received a casein-based formula for 12 months, providing ~25% of estimated daily energy requirements. Sparse partial least squares discriminant analysis (splsda) was applied for group discrimination and identifying sources of variation to identify the impact of PEN. We also investigated the correlation of metabolites with inflammation markers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fecal calprotectin. After 12 months, our results show substantial difference between PEN and non-PEN groups in the metabolome of CD patients in remission or with mild disease activity. Inflammatory markers were associated with individual compounds and chemical classes such as isoprenoids and phospholipids. Identified compounds comprise metabolites produced by human or bacterial metabolism, as well as xenobiotics recognized as flavoring agents and environmental contaminants and their biotransformation products. Further longitudinal studies that also include patients with higher disease activity are warranted to evaluate the suitability of these metabolic biomarkers for predicting disease activity.
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Affiliation(s)
- Jair Gonzalez Marques
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
| | - Engy Shokry
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
| | - Klara Frivolt
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
- Department of Paediatrics, Comenius University Medical School, Bratislava, Slovakia
| | - Katharina Julia Werkstetter
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
| | - Annecarin Brückner
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
| | - Tobias Schwerd
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
| | - Sibylle Koletzko
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
- Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland
| | - Berthold Koletzko
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
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28
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Qin X. More Epidemiological Studies Warranted to Determine the Cause of Inflammatory Bowel Disease. Inflamm Bowel Dis 2021; 27:e43-e44. [PMID: 33331632 DOI: 10.1093/ibd/izaa329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Xiaofa Qin
- GI Biopharma Inc, Westfield, New Jersey, USA
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29
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Xie Y, Zhuang T, Ping Y, Zhang Y, Wang X, Yu P, Duan X. Elevated systemic immune inflammation index level is associated with disease activity in ulcerative colitis patients. Clin Chim Acta 2021; 517:122-126. [PMID: 33662359 DOI: 10.1016/j.cca.2021.02.016] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 02/16/2021] [Accepted: 02/17/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND It has been confirmed that high Systemic immune-inflammation index (SII) levels usually indicate poor outcomes in various diseases, especially on malignancies. However, the clinical significance of the SII in ulcerative colitis (UC) patients is remain unclear. Therefore, the purpose of our paper is to analyze the levels of SII in UC patients and assess the relationship between the SII and disease activity. MATERIALS AND METHODS We studied 187 consecutive patients with UC and 185 age- and sex-matched healthy controls retrospectively. The Mayo scoring system was adopted to evaluate disease activity in UC patients. We collected clinical characteristics and laboratory parameters from hospital electronic medical records. RESULTS The SII levels were significantly higher in UC patients than those in healthy subjects (P < 0.001). Higher SII levels were observed in moderate and severe UC subgroups compared to mild or remission subgroups. Correlation analysis displayed that the SII levels were positively relatived with Mayo score (r = 0.469, P < 0.001), C reactive protein (CRP) (r = 0.480, P < 0.001), and erythrocyte sedimentation rate (ESR) (r = 0.336, P < 0.001), but negatively with haemoglobin (Hb) (r = -0.271, P < 0.001). A multiple linear regression analysis suggested that there was an independent correlation between Mayo score and SII (beta = 0.324, t = 4.241, P < 0.001). The receiver operating characteristic (ROC) curve revealed that the maximum area under the curve (AUC) was 0.711 (95% CI, 0.630-0.791, P < 0.001), and the cut-off value for diagnosing active UC was 485.95, the sensitivity was 0.641, and the specificity was 0.75. CONCLUSIONS We demonstrated that the SII was elevated significantly in UC patients and was closely related to the UC disease activity. In addition, the SII had a high discriminative capacity for active UC.
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Affiliation(s)
- Yiyi Xie
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
| | - Tingting Zhuang
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Ying Ping
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Yingzhi Zhang
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Xuchu Wang
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Pan Yu
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Xiuzhi Duan
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
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30
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Rogler G, Scharl M, Spalinger M, Yilmaz B, Zaugg M, Hersberger M, Schreiner P, Biedermann L, Herfarth H. Diet and Inflammatory Bowel Disease: What Quality Standards Should Be Applied in Clinical and Laboratory Studies? Mol Nutr Food Res 2021; 65:e2000514. [PMID: 33433954 DOI: 10.1002/mnfr.202000514] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 12/21/2020] [Indexed: 12/11/2022]
Abstract
Many patients suffering from inflammatory bowel disease (IBD) follow restrictive diets, as many respective recommendations circulate. Efforts are made to evaluate and summarize the published information, for example, in a recent consensus manuscript by the International Organization for the Study of IBD (IOIBD). However, the standards that should be applied to make claims about dietary effects are poorly defined. In this manuscript, the scientific basis of recommendations for nutritional interventions in IBD is analyzed. Epidemiological evidence on diet in IBD is always biased by numerous factors, and the number of robust dietary intervention studies is limited due to methodological difficulties. Therefore, animal models are used to test hypotheses with respect to dietary factors and intestinal inflammation. Naturally, animal models have limitations, and knowledge of key characteristics of colitis animal models is crucial to understand their advantages and disadvantages. In recent years the important role of the microbiota for IBD and dietary factors has been discovered. Microbiota data are added to many publications on IBD and nutrition. The quality of those data varies largely. Subsequently, quality standards for microbiota analyses also are discussed. Finally, quality requirements to be applied on recommendations for dietary changes in patients with IBD are suggested.
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Affiliation(s)
- Gerhard Rogler
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, University of Zurich 8091, Switzerland
| | - Michael Scharl
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, University of Zurich 8091, Switzerland
| | - Marianne Spalinger
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, University of Zurich 8091, Switzerland
| | - Bahtiyar Yilmaz
- Maurice Müller Laboratories, Department for Biomedical Research, University Clinic of Visceral Surgery and Medicine, Inselspital, University of Bern, Bern, 3010, Switzerland
| | - Michael Zaugg
- Department of Pharmacology and Department of Anesthesiology and Pain Medicine and Cardiovascular Research Centre, University of Alberta, Edmonton, T6G 2G3, Canada
| | - Martin Hersberger
- Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, 8032, Switzerland
| | - Philipp Schreiner
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, University of Zurich 8091, Switzerland
| | - Luc Biedermann
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, University of Zurich 8091, Switzerland
| | - Hans Herfarth
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, 27599-7080, USA
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31
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Abstract
Ulcerative colitis (UC) is a complex chronic, immune-mediated inflammatory disorder of the colon. Factors associated with increased risk of UC include diet, particularly Western diet influences in newly industrialized nations, medications, and lifestyle factors that may influence the host's microbiome or immune response to antigens. Although much evidence identifying potential genetic and host-related factors is currently available, there are still many unanswered questions. As the global UC incidence and prevalence continues to increase, there are multiple opportunities for continued investigation to clarify our understanding of UC, identify potential predictors of disease severity, response to therapy, and novel therapeutic targets.
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Affiliation(s)
- Lillian Du
- Inflammatory Bowel Diseases Center, Cedars-Sinai, 8730 Alden Drive Suite E204, Los Angeles, CA, USA
| | - Christina Ha
- Inflammatory Bowel Diseases Center, Cedars-Sinai, 8730 Alden Drive Suite E204, Los Angeles, CA, USA.
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32
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Qin X. Inhibition of Experimental Colitis by Saccharin in Animals: Should We Dismiss or Raise Concerns Regarding Possible Adverse Effects of Saccharin on Human Gut Microbiota and Health? Inflamm Bowel Dis 2020; 26:e159-e160. [PMID: 32651958 DOI: 10.1093/ibd/izaa180] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Xiaofa Qin
- GI Biopharma Inc., Westfield, New Jersey, USA
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33
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Li X, Liu Y, Wang Y, Li X, Liu X, Guo M, Tan Y, Qin X, Wang X, Jiang M. Sucralose Promotes Colitis-Associated Colorectal Cancer Risk in a Murine Model Along With Changes in Microbiota. Front Oncol 2020; 10:710. [PMID: 32582527 PMCID: PMC7286428 DOI: 10.3389/fonc.2020.00710] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Accepted: 04/15/2020] [Indexed: 12/13/2022] Open
Abstract
Sucralose is a calorie-free high-intensity artificial sweetener that is widely used in thousands of foods and beverages all over the world. Although it was initially regarded as a safe, inert food additive, its adverse effect on gut microbiota and health has drawn more and more attention as evidence accumulates. Studies by us and others revealed that sucralose exacerbated gut damage and inflammation in animal models for inflammatory bowel disease (IBD), including those for both ulcerative colitis, and Crohn's disease. Our study demonstrated that sucralose greatly aggravated dextran sulfate sodium (DSS)-induced colitis along with causing changes in gut microbiota, the gut barrier and impaired inactivation of digestive proteases mediated by deconjugated bilirubin. It is well-documented that IBD greatly increases the risk of colorectal cancer (CRC), the globally third-most-common cancer, which, like IBD, has a high rate in the developed countries. Azoxymethane (AOM)/DSS has been the most commonly used animal model for CRC. In this study, we further explored the effect of sucralose on tumorigenesis and the possible mechanism involved using the AOM/DSS mouse model. First, 1.5 mg/ml sucralose was included in the drinking water for 6 weeks to reach a relatively stable phase of impact on gut microbiota. Then, 10 mg/kg AOM was administered through intraperitoneal injection. Seven days later, 2.5% DSS was put in the drinking water for 5 days, followed by 2 weeks without DSS. The 5 days of DSS was then repeated, and the mice were sacrificed 6 weeks after AOM injection. The results showed that sucralose caused significant increases in the number and size of AOM/DSS-induced colorectal tumors along with changes in other parameters such as body and spleen weight, pathological scores, mortality, fecal β-glucuronidase and digestive proteases, gut barrier molecules, gut microbiota, inflammatory cytokines and pathways (TNFα, IL-1β, IL-6, IL-10, and TLR4/Myd88/NF-κB signaling), and STAT3/VEGF tumor-associated signaling pathway molecules. These results suggest that sucralose may increase tumorigenesis along with dysbiosis of gut microbiota, impaired inactivation of digestive protease, damage to the gut barrier, and exacerbated inflammation.
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Affiliation(s)
- Xueting Li
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, China
| | - Yuanli Liu
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, China
| | - Yan Wang
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, China
| | - Xue Li
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, China
| | - Xinran Liu
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, China
| | - Mengru Guo
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, China
| | - Yiwei Tan
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, China
| | - Xiaofa Qin
- GI Biopharma Inc., Westfield, NJ, United States
| | - Xiuhong Wang
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, China
| | - Mingshan Jiang
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
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Rondanelli M, Lamburghini S, Faliva MA, Peroni G, Riva A, Allegrini P, Spadaccini D, Gasparri C, Iannello G, Infantino V, Alalwan TA, Perna S, Miccono A. A food pyramid, based on a review of the emerging literature, for subjects with inflammatory bowel disease. ACTA ACUST UNITED AC 2020; 68:17-46. [PMID: 32499202 DOI: 10.1016/j.endinu.2020.01.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 12/14/2019] [Accepted: 01/08/2020] [Indexed: 02/07/2023]
Abstract
Emerging literature suggests that diet plays an important modulatory role in inflammatory bowel disease (IBD) through the management of inflammation and oxidative stress. The aim of this narrative review is to evaluate the evidence collected up till now regarding optimum diet therapy for IBD and to design a food pyramid for these patients. The pyramid shows that carbohydrates should be consumed every day (3 portions), together with tolerated fruits and vegetables (5 portions), yogurt (125ml), and extra virgin olive oil; weekly, fish (4 portions), white meat (3 portions), eggs (3 portions), pureed legumes (2 portions), seasoned cheeses (2 portions), and red or processed meats (once a week). At the top of the pyramid, there are two pennants: the red one means that subjects with IBD need some personalized supplementation and the black one means that there are some foods that are banned. The food pyramid makes it easier for patients to decide what they should eat.
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Affiliation(s)
- Mariangela Rondanelli
- IRCCS Mondino Foundation, Pavia, Department of Public Health, Experimental and Forensic Medicine, Unit of Human and Clinical Nutrition, University of Pavia, Pavia 27100, Italy
| | - Silvia Lamburghini
- University of Pavia, Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona, Pavia 27100, Italy
| | - Milena A Faliva
- University of Pavia, Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona, Pavia 27100, Italy
| | - Gabriella Peroni
- University of Pavia, Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona, Pavia 27100, Italy
| | - Antonella Riva
- Research and Development Unit, Indena, Milan 20146, Italy
| | | | - Daniele Spadaccini
- University of Pavia, Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona, Pavia 27100, Italy
| | - Clara Gasparri
- University of Pavia, Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona, Pavia 27100, Italy
| | - Giancarlo Iannello
- General Management, Azienda di Servizi alla Persona "Istituto Santa Margherita", Pavia 27100, Italy
| | - Vittoria Infantino
- University of Bari Aldo Moro, Department of Biomedical Science and Human Oncology, Section of Human Nutrition, Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona, Pavia 27100, Italy.
| | - Tariq A Alalwan
- Department of Biology, College of Science, University of Bahrain, Sakhir Campus, P.O. Box 32038, Bahrain
| | - Simone Perna
- Department of Biology, College of Science, University of Bahrain, Sakhir Campus, P.O. Box 32038, Bahrain
| | - Alessandra Miccono
- University of Pavia, Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona, Pavia 27100, Italy
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Levine A, Rhodes JM, Lindsay JO, Abreu MT, Kamm MA, Gibson PR, Gasche C, Silverberg MS, Mahadevan U, Boneh RS, Wine E, Damas OM, Syme G, Trakman GL, Yao CK, Stockhamer S, Hammami MB, Garces LC, Rogler G, Koutroubakis IE, Ananthakrishnan AN, McKeever L, Lewis JD. Dietary Guidance From the International Organization for the Study of Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol 2020; 18:1381-1392. [PMID: 32068150 DOI: 10.1016/j.cgh.2020.01.046] [Citation(s) in RCA: 181] [Impact Index Per Article: 36.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 12/21/2019] [Accepted: 01/24/2020] [Indexed: 02/07/2023]
Abstract
Recent evidence points to a plausible role of diet and the microbiome in the pathogenesis of both Crohn's disease (CD) and Ulcerative Colitis (UC). Dietary therapies based on exclusion of table foods and replacement with nutritional formulas and/or a combination of nutritional formulas and specific table foods may induce remission in CD. In UC, specific dietary components have also been associated with flare of disease. While evidence of varying quality has identified potential harmful or beneficial dietary components, physicians and patients at the present time do not have guidance as to which foods are safe, may be protective or deleterious for these diseases. The current document has been compiled by the nutrition cluster of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) based on the best current evidence to provide expert opinion regarding specific dietary components, food groups and food additives that may be prudent to increase or decrease in the diet of patients with inflammatory bowel diseases to control and prevent relapse of inflammatory bowel diseases.
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Affiliation(s)
- Arie Levine
- Pediatric IBD Center, Wolfson Medical Center Holon, Tel Aviv University, Tel Aviv, Israel
| | - Jonathan M Rhodes
- Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
| | - James O Lindsay
- Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom
| | - Maria T Abreu
- Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida
| | - Michael A Kamm
- St Vincent's Hospital and University of Melbourne, Melbourne, Australia
| | - Peter R Gibson
- Monash University and Alfred Health, Melbourne, Australia
| | | | - Mark S Silverberg
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, Canada
| | - Uma Mahadevan
- University of California, San Francisco, San Francisco, California
| | - Rotem Sigall Boneh
- Pediatric IBD Center, Wolfson Medical Center Holon, Tel Aviv University, Tel Aviv, Israel
| | - Eyton Wine
- Department of Pediatrics, University of Alberta, Alberta, Canada; Department of Physiology, University of Alberta, Alberta, Canada
| | - Oriana M Damas
- Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida
| | - Graeme Syme
- The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom
| | - Gina L Trakman
- St Vincent's Hospital and University of Melbourne, Melbourne, Australia
| | - Chu Kion Yao
- Monash University and Alfred Health, Melbourne, Australia
| | - Stefanie Stockhamer
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, Canada
| | | | - Luis C Garces
- Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida
| | | | | | | | - Liam McKeever
- Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - James D Lewis
- Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
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Han MK, Anderson R, Viennois E, Merlin D. Examination of food consumption in United States adults and the prevalence of inflammatory bowel disease using National Health Interview Survey 2015. PLoS One 2020; 15:e0232157. [PMID: 32324818 PMCID: PMC7179926 DOI: 10.1371/journal.pone.0232157] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Accepted: 04/09/2020] [Indexed: 12/20/2022] Open
Abstract
Various diets and food components have been implicated as one of the environmental factors associated with inflammatory bowel disease (IBD). Patients are often recommended nutritional guidelines to manage disease symptoms. However, the current food consumption pattern of US adults with IBD that are nationally representative is unclear. A secondary analysis of National Health Interview Survey 2015 was performed to characterize the estimated US adults with IBD and their food intake and consumption frequency using bivariate and multivariate logistic regression. Fries were consumed by a greater number of people with IBD. IBD population drank less 100% fruit juice and ate more cheese and cookies than non-IBD population. Intake of fries (OR 1.60, 95% CI 1.14-2.25) and sports and energy drinks (OR 1.46, 95% CI 1.07-1.97) and more frequent drinking of regular soda were significantly associated with the likelihood of having been told one have IBD, while popcorn (OR 0.73, 95% CI 0.548-0.971) and milk (OR 0.70, 95% CI 0.497-0.998) were associated with smaller odds, adjusting for covariates. Foods typically labeled as junk food were positively associated with IBD. Nonetheless, of the assessed 26 foods, we found eating patterns between IBD and non-IBD population to be mostly analogous. It is unclear whether the results reflect potential change in food intake in IBD population long before the survey interview. Understanding the role of food intake in IBD risk/prevalence would benefit from identifying other environmental factors (i.e. food desert), food processing (i.e. frying), and potential bioactive food components that can induce intestinal inflammation that can increase the individual's susceptibility to IBD.
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Affiliation(s)
- Moon K. Han
- Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Center for Inflammation, Immunity and Infection, Digestive Disease Research Group, Georgia State University, Atlanta, Georgia, United States of America
| | - Raeda Anderson
- Department of Research and Engagement, Georgia State University, Atlanta, Georgia, United States of America
| | - Emilie Viennois
- Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Center for Inflammation, Immunity and Infection, Digestive Disease Research Group, Georgia State University, Atlanta, Georgia, United States of America
| | - Didier Merlin
- Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Center for Inflammation, Immunity and Infection, Digestive Disease Research Group, Georgia State University, Atlanta, Georgia, United States of America
- Atlanta Veterans Affairs Medical Center, Decatur, Georgia, United States of America
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Kriaa A, Jablaoui A, Mkaouar H, Akermi N, Maguin E, Rhimi M. Serine proteases at the cutting edge of IBD: Focus on gastrointestinal inflammation. FASEB J 2020; 34:7270-7282. [PMID: 32307770 DOI: 10.1096/fj.202000031rr] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 03/27/2020] [Accepted: 03/28/2020] [Indexed: 12/15/2022]
Abstract
Serine proteases have been long recognized to coordinate many physiological processes and play key roles in regulating the inflammatory response. Accordingly, their dysregulation has been regularly associated with several inflammatory disorders and suggested as a central mechanism in the pathophysiology of digestive inflammation. So far, studies addressing the proteolytic homeostasis in the gut have mainly focused on host serine proteases as candidates of interest, while largely ignoring the potential contribution of their bacterial counterparts. The human gut microbiota comprises a complex ecosystem that contributes to host health and disease. Yet, our understanding of microbially produced serine proteases and investigation of whether they are causally linked to IBD is still in its infancy. In this review, we highlight recent advances in the emerging roles of host and bacterial serine proteases in digestive inflammation. We also discuss the application of available tools in the gut to monitor disease-related serine proteases. An exhaustive representation and understanding of such functional potential would help in closing existing gaps in mechanistic knowledge.
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Affiliation(s)
- Aicha Kriaa
- Microbiota Interaction with Human and Animal Team (MIHA), Micalis Institute, AgroParisTech, Université Paris-Saclay, INRAE, Jouy-en-Josas, France
| | - Amin Jablaoui
- Microbiota Interaction with Human and Animal Team (MIHA), Micalis Institute, AgroParisTech, Université Paris-Saclay, INRAE, Jouy-en-Josas, France
| | - Héla Mkaouar
- Microbiota Interaction with Human and Animal Team (MIHA), Micalis Institute, AgroParisTech, Université Paris-Saclay, INRAE, Jouy-en-Josas, France
| | - Nizar Akermi
- Microbiota Interaction with Human and Animal Team (MIHA), Micalis Institute, AgroParisTech, Université Paris-Saclay, INRAE, Jouy-en-Josas, France
| | - Emmanuelle Maguin
- Microbiota Interaction with Human and Animal Team (MIHA), Micalis Institute, AgroParisTech, Université Paris-Saclay, INRAE, Jouy-en-Josas, France
| | - Moez Rhimi
- Microbiota Interaction with Human and Animal Team (MIHA), Micalis Institute, AgroParisTech, Université Paris-Saclay, INRAE, Jouy-en-Josas, France
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Saccharin Supplementation Inhibits Bacterial Growth and Reduces Experimental Colitis in Mice. Nutrients 2020; 12:nu12041122. [PMID: 32316544 PMCID: PMC7230785 DOI: 10.3390/nu12041122] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 04/08/2020] [Accepted: 04/14/2020] [Indexed: 12/13/2022] Open
Abstract
Non-caloric artificial sweeteners are frequently discussed as components of the “Western diet”, negatively modulating intestinal homeostasis. Since the artificial sweetener saccharin is known to depict bacteriostatic and microbiome-modulating properties, we hypothesized oral saccharin intake to influence intestinal inflammation and aimed at delineating its effect on acute and chronic colitis activity in mice. In vitro, different bacterial strains were grown in the presence or absence of saccharin. Mice were supplemented with saccharin before or after induction of acute or chronic colitis using dextran sodium sulfate (DSS) and the extent of colitis was assessed. Ex vivo, intestinal inflammation, fecal bacterial load and composition were studied by immunohistochemistry analyses, quantitative PCR, 16 S RNA PCR or next generation sequencing in samples collected from analyzed mice. In vitro, saccharin inhibited bacterial growth in a species-dependent manner. In vivo, oral saccharin intake reduced fecal bacterial load and altered microbiome composition, while the intestinal barrier was not obviously affected. Of note, DSS-induced colitis activity was significantly improved in mice after therapeutic or prophylactic treatment with saccharin. Together, this study demonstrates that oral saccharin intake decreases intestinal bacteria count and hence encompasses the capacity to reduce acute and chronic colitis activity in mice.
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TLC-Bioautography as a fast and cheap screening method for the detection of α-chymotrypsin inhibitors in crude plant extracts. J Biotechnol 2020; 313:11-17. [DOI: 10.1016/j.jbiotec.2020.02.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 02/28/2020] [Accepted: 02/28/2020] [Indexed: 01/22/2023]
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40
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Advances in colon-targeted nano-drug delivery systems: challenges and solutions. Arch Pharm Res 2020; 43:153-169. [DOI: 10.1007/s12272-020-01219-0] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 01/20/2020] [Indexed: 12/16/2022]
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Inflammatory bowel disease and targeted oral anti-TNFα therapy. ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY 2020; 119:157-198. [PMID: 31997768 DOI: 10.1016/bs.apcsb.2019.08.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Antibodies have provided invaluable treatment options for many diseases, with immunotherapy revolutionising the treatment of several inflammatory disorders including inflammatory bowel disease (IBD). Accumulating evidence suggests that IBD results from an inappropriate response to intestinal microbes and environmental factors in genetically susceptible individuals, with overactivity of the pro-inflammatory pathways. On a pathophysiological level, IBD is a complex disease with intestinal fibrosis, stenosis and an increased incidence of cancer observed in those whose disease is inadequately controlled over time. Regulating the actions of the pro-inflammatory cytokine human tumor necrosis factor-alpha (hTNFα) through the use of anti-TNFα monoclonal antibodies (e.g. infliximab, certolizumab, adalimumab and golimumab) has proven an effective intervention for IBD with their increased use a testament of their effectiveness. These agents are administered systemically thereby causing their distribution throughout the body in a condition that is localised to the gastrointestinal (GI) tract. Immunogenicity, the induction of anti-drug antibodies (ADAs), serum sickness and other undesirable side effects limit their use, whilst up to 50% of patients do not respond to initial therapy. Diseases confined to the GI tract are ideal for targeting by oral therapy which mitigates side effects and allows for lower doses to be administered. Several oral anti-TNFα agents have been investigated with success but are not yet in general clinical use. This partially reflects the fact that the oral administration of antibodies has many barriers including the harsh environment of the GI tract and the presence of enzymes including pepsin, trypsin and chymotrypsin in the intestine which provide significant challenges to targeted oral therapy.
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Parisio C, Lucarini E, Micheli L, Toti A, Di Cesare Mannelli L, Antonini G, Panizzi E, Maidecchi A, Giovagnoni E, Lucci J, Ghelardini C. Researching New Therapeutic Approaches for Abdominal Visceral Pain Treatment: Preclinical Effects of an Assembled System of Molecules of Vegetal Origin. Nutrients 2019; 12:nu12010022. [PMID: 31861862 PMCID: PMC7019336 DOI: 10.3390/nu12010022] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 11/20/2019] [Accepted: 12/06/2019] [Indexed: 12/12/2022] Open
Abstract
Abdominal pain is a frequent symptom of irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBDs). Although the knowledge of these pathologies is progressing, new therapeutic strategies continue to be investigated. In the present study, the effect of a system of molecules of natural origin (a medical device according to EU Directive 93/42/EC, engineered starting from Boswellia serrata resins, Aloe vera polysaccharides and Matricaria chamomilla and Melissa officinalis polyphenols) was evaluated against the intestinal damage and visceral pain development in DNBS-induced colitis model in rats. The system (250 and 500 mg kg−1) was orally administered once daily, starting three days before the injection of 2,4-dinitrobenzenesulfonic acid (DNBS) and for 14 days thereafter. The viscero-motor response (VMR) to colon-rectal balloon distension (CRD) was used as measure of visceral sensitivity. The product significantly reduced the VMR of DNBS-treated animals. Its effect on pain threshold was better than dexamethasone and mesalazine, and not lower than amitriptyline and otilonium bromide. At microscopic and macroscopic level, the tested system was more effective in protecting the intestinal mucosa than dexamethasone and mesalazine, promoting the healing of tissue lesions. Therefore, we suggest that the described system of molecules of natural origin may represent a therapeutic option to manage painful bowel diseases.
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Affiliation(s)
- Carmen Parisio
- Department of Neuroscience, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy; (C.P.); (E.L.); (L.M.); (A.T.); (C.G.)
| | - Elena Lucarini
- Department of Neuroscience, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy; (C.P.); (E.L.); (L.M.); (A.T.); (C.G.)
| | - Laura Micheli
- Department of Neuroscience, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy; (C.P.); (E.L.); (L.M.); (A.T.); (C.G.)
| | - Alessandra Toti
- Department of Neuroscience, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy; (C.P.); (E.L.); (L.M.); (A.T.); (C.G.)
| | - Lorenzo Di Cesare Mannelli
- Department of Neuroscience, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy; (C.P.); (E.L.); (L.M.); (A.T.); (C.G.)
- Correspondence: ; Tel.: +39-055-275-8395
| | - Giulia Antonini
- Aboca SpA Società Agricola, Innovation & Medical Science Division, Loc. Aboca 20, 52037 Sansepolcro (AR), Italy; (G.A.); (E.P.); (A.M.); (E.G.); (J.L.)
| | - Elena Panizzi
- Aboca SpA Società Agricola, Innovation & Medical Science Division, Loc. Aboca 20, 52037 Sansepolcro (AR), Italy; (G.A.); (E.P.); (A.M.); (E.G.); (J.L.)
- Natural Bio-Medicine SpA, Loc. Aboca 20, 52037 Sansepolcro (AR), Italy
| | - Anna Maidecchi
- Aboca SpA Società Agricola, Innovation & Medical Science Division, Loc. Aboca 20, 52037 Sansepolcro (AR), Italy; (G.A.); (E.P.); (A.M.); (E.G.); (J.L.)
| | - Emiliano Giovagnoni
- Aboca SpA Società Agricola, Innovation & Medical Science Division, Loc. Aboca 20, 52037 Sansepolcro (AR), Italy; (G.A.); (E.P.); (A.M.); (E.G.); (J.L.)
| | - Jacopo Lucci
- Aboca SpA Società Agricola, Innovation & Medical Science Division, Loc. Aboca 20, 52037 Sansepolcro (AR), Italy; (G.A.); (E.P.); (A.M.); (E.G.); (J.L.)
- Natural Bio-Medicine SpA, Loc. Aboca 20, 52037 Sansepolcro (AR), Italy
| | - Carla Ghelardini
- Department of Neuroscience, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy; (C.P.); (E.L.); (L.M.); (A.T.); (C.G.)
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Qin X. Impaired Inactivation of Digestive Proteases in Lower Gut Due to Inhibition of Gut Bacteria by Food Additives Such as Saccharin and Sucralose as Main Cause of Inflammatory Bowel Disease: A Two-Decades-Long Hypothesis Warrants Testing. Inflamm Bowel Dis 2019; 25:e141. [PMID: 31504530 DOI: 10.1093/ibd/izz187] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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A high-sugar diet rapidly enhances susceptibility to colitis via depletion of luminal short-chain fatty acids in mice. Sci Rep 2019; 9:12294. [PMID: 31444382 PMCID: PMC6707253 DOI: 10.1038/s41598-019-48749-2] [Citation(s) in RCA: 133] [Impact Index Per Article: 22.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Accepted: 07/30/2019] [Indexed: 02/06/2023] Open
Abstract
Western-style diets have been implicated in triggering inflammatory bowel disease activity. The aim of this study was to identify the effect of a short-term diet high in sugar on susceptibility to colitis. Adult wild-type mice were placed on chow or a high sugar diet (50% sucrose) ± acetate. After two days of diet, mice were treated with dextran sodium sulfate (DSS) to induce colitis. Disease severity was assessed daily. Colonic tissues were analyzed for cytokine expression using the MesoScale discovery platform. Intestinal dextran permeability and serum lipopolysaccharide levels (LPS) were measured. Gut microbiota were analyzed by 16s rRNA sequencing and short chain fatty acid (SCFA) concentrations by gas chromatography. Bone marrow-derived macrophages (BMDM) were incubated with LPS and cytokine secretion measured. Mice on a high sugar diet had increased gut permeability, decreased microbial diversity and reduced SCFA. BMDM derived from high sugar fed mice were highly responsive to LPS. High sugar fed mice had increased susceptibility to colitis and pro-inflammatory cytokine concentrations. Oral acetate significantly attenuated colitis in mice by restoring permeability. In conclusion, short term exposure to a high sugar diet increases susceptibility to colitis by reducing short-chain fatty acids and increasing gut permeability.
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Roberts-Thomson IC, Bryant RV, Costello SP. Uncovering the cause of ulcerative colitis. JGH Open 2019; 3:274-276. [PMID: 31406918 PMCID: PMC6684508 DOI: 10.1002/jgh3.12216] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 05/22/2019] [Indexed: 12/15/2022]
Abstract
The cause of ulcerative colitis still remains unclear. The most popular hypothesis is that colitis develops because of a complex interaction of genetic, microbial, environmental, and immunologic factors. This editorial summarizes the widely accepted hypothesis and comments on a variation of this hypothesis promoted by Dr Roediger.
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Affiliation(s)
| | - Robert V Bryant
- School of Medicine University of Adelaide Adelaide South Australia Australia.,Department of Gastroenterology and Hepatology Queen Elizabeth Hospital Adelaide South Australia Australia
| | - Samuel P Costello
- School of Medicine University of Adelaide Adelaide South Australia Australia.,Department of Gastroenterology and Hepatology Queen Elizabeth Hospital Adelaide South Australia Australia
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Novel polyurethane-based nanoparticles of infliximab to reduce inflammation in an in-vitro intestinal epithelial barrier model. Int J Pharm 2019; 565:533-542. [PMID: 31085256 DOI: 10.1016/j.ijpharm.2019.05.025] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Revised: 05/01/2019] [Accepted: 05/10/2019] [Indexed: 12/27/2022]
Abstract
In this study we examined the potential of novel biodegradable polymers of polyesterurethane (PU), and its PEGylated (PU-PEG) form as nanocarriers of Infliximab (INF), to treat inflammation in an in-vitro epithelial model. Nanoparticles (NPs) formulated were of average size of 200-287 nm. INF loading of NPs (INF-NPs) resulted in an increase in size and zeta potential. No cytotoxicity was observed for any of the NPs. Cellular interaction and uptake of PU NPs were similar compared with polycaprolactone (PCL) NPs and significantly higher to Poly(lactic-co-glycolic) acid (PLGA) NPs. Cellular interaction was higher for corresponding PEG-NPs. INF-PU and INF-PU-PEG NPs showed a rapid rate and extent of recovery of the epithelial barrier function in inflamed Caco-2 cell monolayers and decreased cytokine levels in inflamed monocytes. Results obtained in this study are promising and the potential of PU and PU-PEG NPs for drug delivery and targeting to treat gastrointestinal inflammation warrants further investigation.
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Di Narzo AF, Brodmerkel C, Telesco SE, Argmann C, Peters LA, Li K, Kidd B, Dudley J, Cho J, Schadt EE, Kasarskis A, Dobrin R, Hao K. High-Throughput Identification of the Plasma Proteomic Signature of Inflammatory Bowel Disease. J Crohns Colitis 2019; 13:462-471. [PMID: 30445421 PMCID: PMC6441306 DOI: 10.1093/ecco-jcc/jjy190] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The molecular aetiology of inflammatory bowel disease [IBD] and its two subtypes, ulcerative colitis [UC] and Crohn's disease [CD], have been carefully investigated at genome and transcriptome levels. Recent advances in high-throughput proteome quantification has enabled comprehensive large-scale plasma proteomics studies of IBD. METHODS The study used two cohorts: [1] The CERTIFI-cohort: 42 samples from the CERTIFI trial of anti-TNFα-refractory CD patients; [2] the PROgECT-UNITI-HCs cohort: 46 UC samples of the PROgECT study, 84 CD samples of the UNITI I and UNITI II studies, and 72 healthy controls recruited in Mount Sinai Hospital, New York, USA. The plasma proteome for these two cohorts was quantified using high-throughput platforms. RESULTS For the PROgECT-UNITI-HCs cohort, we measured a total of 1310 proteins. Of these, 493 proteins showed different plasma levels in IBD patients to the plasma levels in controls at 10% false discovery rate [FDR], among which 11 proteins had a fold change greater than 2. The proteins upregulated in IBD were associated with immunity functionality, whereas the proteins downregulated in IBD were associated with nutrition and metabolism. The proteomic profiles were very similar between UC and CD. In the CERTIFI cohort, 1014 proteins were measured, and it was found that the plasma protein level had little correlation with the blood or intestine transcriptomes. CONCLUSIONS We report the largest proteomics study to date on IBD and controls. A large proportion of plasma proteins are altered in IBD, which provides insights into the disease aetiology and indicates a potential for biomarker discovery.
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Affiliation(s)
- Antonio F Di Narzo
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | | | - Carmen Argmann
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Lauren A Peters
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Sema4, a Mount Sinai venture, Stamford, CT, USA
| | | | - Brian Kidd
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Joel Dudley
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Judy Cho
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Eric E Schadt
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Sema4, a Mount Sinai venture, Stamford, CT, USA
| | - Andrew Kasarskis
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Ke Hao
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Respiratory Medicine, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China
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M'Koma AE. The Multifactorial Etiopathogeneses Interplay of Inflammatory Bowel Disease: An Overview. GASTROINTESTINAL DISORDERS 2019; 1:75-105. [PMID: 37577036 PMCID: PMC10416806 DOI: 10.3390/gidisord1010007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The gastrointestinal system where inflammatory bowel disease occurs is central to the immune system where the innate and the adaptive/acquired immune systems are balanced in interactions with gut microbes under homeostasis conditions. This article overviews the high-throughput research screening on multifactorial interplay between genetic risk factors, the intestinal microbiota, urbanization, modernization, Westernization, the environmental influences and immune responses in the etiopathogenesis of inflammatory bowel disease in humans. Inflammatory bowel disease is an expensive multifactorial debilitating disease that affects thousands new people annually worldwide with no known etiology or cure. The conservative therapeutics focus on the established pathology where the immune dysfunction and gut injury have already happened but do not preclude or delay the progression. Inflammatory bowel disease is evolving globally and has become a global emergence disease. It is largely known to be a disease in industrial-urbanized societies attributed to modernization and Westernized lifestyle associated with environmental factors to genetically susceptible individuals with determined failure to process certain commensal antigens. In the developing nations, increasing incidence and prevalence of inflammatory bowel disease (IBD) has been associated with rapid urbanization, modernization and Westernization of the population. In summary, there are identified multiple associations to host exposures potentiating the landscape risk hazards of inflammatory bowel disease trigger, that include: Western life-style and diet, host genetics, altered innate and/or acquired/adaptive host immune responses, early-life microbiota exposure, change in microbiome symbiotic relationship (dysbiosis/dysbacteriosis), pollution, changing hygiene status, socioeconomic status and several other environmental factors have long-standing effects/influence tolerance. The ongoing multipronged robotic studies on gut microbiota composition disparate patterns between the rural vs. urban locations may help elucidate and better understand the contribution of microbiome disciplines/ecology and evolutionary biology in potentially protecting against the development of inflammatory bowel disease.
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Affiliation(s)
- Amosy E M'Koma
- Meharry Medical College School of Medicine, Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Nashville, TN 37208, USA
- Vanderbilt University School of Medicine, Department of Surgery, Colon and Rectal Surgery, Nashville, TN 37232, USA
- The American Society of Colon and Rectal Surgeons (ASCRS), Arlington Heights, IL 60005, USA
- The American Gastroenterological Association (AGA), Bethesda, MD 20814, USA
- Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University Medical Center, Nashville, TN 37232, USA
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Qin X. May Dysbiosis Caused by Dietary Chemicals Such as Sucralose and Saccharin Be More Detrimental to the Gut and Health Than Antibiotics? How? Inflamm Bowel Dis 2019; 25:e20. [PMID: 29850815 DOI: 10.1093/ibd/izy198] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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A Novel Rare Missense Variation of the NOD2 Gene: Evidencesof Implication in Crohn's Disease. Int J Mol Sci 2019; 20:ijms20040835. [PMID: 30769939 PMCID: PMC6412783 DOI: 10.3390/ijms20040835] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Revised: 01/23/2019] [Accepted: 02/03/2019] [Indexed: 11/17/2022] Open
Abstract
The NOD2 gene, involved in innate immune responses to bacterial peptidoglycan, has been found to be closely associated with Crohn’s Disease (CD), with an Odds Ratio ranging from 3–36. Families with three or more CD-affected members were related to a high frequency of NOD2 gene variations, such as R702W, G908R, and 1007fs, and were reported in the EPIMAD Registry. However, some rare CD multiplex families were described without identification of common NOD2 linked-to-disease variations. In order to identify new genetic variation(s) closely linked with CD, whole exome sequencing was performed on available subjects, comprising four patients in two generations affected with Crohn’s disease without R702W and G908R variation and three unaffected related subjects. A rare and, not yet, reported missense variation of the NOD2 gene, N1010K, was detected and co-segregated across affected patients. In silico evaluation and modelling highlighted evidence for an adverse effect of the N1010K variation with regard to CD. Moreover, cumulative characterization of N1010K and 1007fs as a compound heterozygous state in two, more severe CD family members strongly suggests that N1010K could well be a new risk factor involved in Crohn’s disease genetic susceptibility.
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