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IBS is characterized by a variety of distressing symptoms, including cramping, abdominal pain, and irregular bowel movements, underlined by an intricate interplay of immune system dysfunction in its pathology. Numerous studies highlight an increased cellular immune response, with elevated levels of proinflammatory cytokines, mucosal alterations due to immune imbalance, and visceral hypersensitivity. Notably, studies indicate increased levels of proinflammatory cytokines, immune imbalances that lead to mucosal changes, and heightened visceral sensitivity. The roles of effector and regulatory T cells are particularly intriguing, as their modification appears to amplify inflammation and may even contribute to autoimmune disorders. This overview of systematic reviews explores the connections between IBS and immune responses, with a focus on immune cell alterations and proliferation of lymphocytes and mast cells in affected individuals. Furthermore, we explore various aspects of IBS management, including its pharmacological approaches. A systematic search of PubMed and Web of Science yielded 676 articles, which were ultimately narrowed down to 9 key studies that met our inclusion criteria. These studies collectively underscore the activation of the immune system with the degranulation of the mast cells in patients with IBS, where the release of inflammatory mediators can compromise intestinal permeability, exacerbating symptoms further. Additionally, we examine the multifaceted management strategies for IBS, emphasizing the potential therapeutic benefits of dietary polyphenols as antioxidants. The present study aims to enhance our understanding of IBS and offer insights into more effective treatment strategies for this challenging condition.<\/jats:p>","DOI":"10.3390\/ijms252211993","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T04:02:54Z","timestamp":1731038574000},"page":"11993","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Multiple Aspects of Irritable Bowel Syndrome and the Role of the Immune System: An Overview of Systematic Reviews with a Focus on Polyphenols"],"prefix":"10.3390","volume":"25","author":[{"given":"Lucia Carmela","family":"Passacatini","sequence":"first","affiliation":[{"name":"IRCCS San Raffaele Roma, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6756-6530","authenticated-orcid":false,"given":"Sara","family":"Ilari","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Roma, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0000-4015","authenticated-orcid":false,"given":"Saverio","family":"Nucera","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Scarano","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2345-6751","authenticated-orcid":false,"given":"Roberta","family":"Macr\u00ec","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosamaria","family":"Caminiti","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Serra","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0930-8987","authenticated-orcid":false,"given":"Francesca","family":"Oppedisano","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Maiuolo","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4199-207X","authenticated-orcid":false,"given":"Ernesto","family":"Palma","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Malafoglia","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Roma, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1823-2195","authenticated-orcid":false,"given":"Carlo","family":"Tomino","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Roma, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Fini","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Roma, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Mollace","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1047-4467","authenticated-orcid":false,"given":"Carolina","family":"Muscoli","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S101","DOI":"10.1038\/533S101a","article-title":"Irritable bowel syndrome","volume":"533","author":"Grayson","year":"2016","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s00406-014-0502-z","article-title":"Anxiety and depression comorbidities in irritable bowel syndrome (IBS): A systematic review and meta-analysis","volume":"264","author":"Fond","year":"2014","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2147\/CLEP.S40245","article-title":"The epidemiology of irritable bowel syndrome","volume":"6","author":"Card","year":"2014","journal-title":"CLEP"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1097\/GME.0000000000002150","article-title":"Effect of ospemifene on vaginal microbiome in postmenopausal women with vulvovaginal atrophy","volume":"30","author":"Alvisi","year":"2023","journal-title":"Menopause"},{"key":"ref_5","first-page":"1275","article-title":"Exploring the impact of endometriosis on women\u2019s lives: A qualitative study in Iran","volume":"8","author":"Namazi","year":"2020","journal-title":"Nurs."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"544","DOI":"10.5056\/jnm18082","article-title":"Sex-Gender Differences in Irritable Bowel Syndrome","volume":"24","author":"Kim","year":"2018","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/1751-2980.12988","article-title":"Sex-based differences in fecal short-chain fatty acid and gut microbiota in irritable bowel syndrome patients","volume":"22","author":"Sun","year":"2021","journal-title":"J. Dig. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1046\/j.1365-2249.2001.01443.x","article-title":"Patients with inflammatory bowel disease (IBD) reveal increased induction capacity of intracellular interferon-gamma (IFN-gamma) in peripheral CD8+ lymphocytes co-cultured with intestinal epithelial cells","volume":"123","author":"Bisping","year":"2001","journal-title":"Clin. Exp. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/ajg.2010.512","article-title":"Small Bowel Homing T Cells Are Associated With Symptoms and Delayed Gastric Emptying in Functional Dyspepsia","volume":"106","author":"Liebregts","year":"2011","journal-title":"Am. J. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1177\/1099800402004001005","article-title":"Natural Killer Cell Function and Psychological Distress in Women with and without Irritable Bowel Syndrome","volume":"4","author":"Motzer","year":"2002","journal-title":"Biol. Res. For. Nurs."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e12861","DOI":"10.1111\/sji.12861","article-title":"New avenues for melanoma immunotherapy: Natural Killer cells?","volume":"91","author":"Cristiani","year":"2020","journal-title":"Scand. J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"eabg5016","DOI":"10.1126\/sciadv.abg5016","article-title":"High-salt diet mediates interplay between NK cells and gut microbiota to induce potent tumor immunity","volume":"7","author":"Rizvi","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4103\/1319-3767.173753","article-title":"The implications of oxidative stress and antioxidant therapies in Inflammatory Bowel Disease: Clinical aspects and animal models","volume":"22","author":"Balmus","year":"2016","journal-title":"Saudi J. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Vannucchi, M., and Evangelista, S. (2018). Experimental Models of Irritable Bowel Syndrome and the Role of the Enteric Neurotransmission. JCM, 7.","DOI":"10.3390\/jcm7010004"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/s41395-018-0377-0","article-title":"Evidence for Local and Systemic Immune Activation in Functional Dyspepsia and the Irritable Bowel Syndrome: A Systematic Review","volume":"114","author":"Burns","year":"2019","journal-title":"Am. J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"110694","DOI":"10.1016\/j.jpsychores.2021.110694","article-title":"Emotional stress responsivity of patients with IBS\u2013a systematic review","volume":"153","author":"Schaper","year":"2022","journal-title":"J. Psychosom. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"48","DOI":"10.12809\/eaap1877","article-title":"Neurocognitive Characteristics of Individuals with Irritable Bowel Syndrome","volume":"29","author":"Wong","year":"2019","journal-title":"East. Asian Arch. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Garofalo, C., Cristiani, C.M., Ilari, S., Passacatini, L.C., Malafoglia, V., Viglietto, G., Maiuolo, J., Oppedisano, F., Palma, E., and Tomino, C. (2023). Fibromyalgia and Irritable Bowel Syndrome Interaction: A Possible Role for Gut Microbiota and Gut-Brain Axis. Biomedicines, 11.","DOI":"10.3390\/biomedicines11061701"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1097\/00006842-200109000-00014","article-title":"Psychological and Physiological Responses to Postprandial Mental Stress in Women With the Irritable Bowel Syndrome","volume":"63","author":"Elsenbruch","year":"2001","journal-title":"Psychosom. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"105640","DOI":"10.1016\/j.psyneuen.2021.105640","article-title":"The gut microbiota-brain axis, psychobiotics and its influence on brain and behaviour: A systematic review","volume":"137","author":"Barrio","year":"2022","journal-title":"Psychoneuroendocrinology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/s41579-020-00460-0","article-title":"The gut microbiota\u2013brain axis in behaviour and brain disorders","volume":"19","author":"Morais","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"616883","DOI":"10.3389\/fnins.2021.616883","article-title":"The Contribution of Gut Microbiota\u2013Brain Axis in the Development of Brain Disorders","volume":"15","author":"Maiuolo","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Maiuolo, J., Musolino, V., Gliozzi, M., Carresi, C., Scarano, F., Nucera, S., Scicchitano, M., Oppedisano, F., Bosco, F., and Macri, R. (2022). Involvement of the Intestinal Microbiota in the Appearance of Multiple Sclerosis: Aloe vera and Citrus bergamia as Potential Candidates for Intestinal Health. Nutrients, 14.","DOI":"10.3390\/nu14132711"},{"key":"ref_24","first-page":"6","article-title":"Health care practices in ancient Greece: The Hippocratic ideal","volume":"7","author":"Kleisiaris","year":"2014","journal-title":"J. Med. Ethics Hist. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/0165-0173(90)90012-D","article-title":"Physiological and behavioral responses to corticotropin-releasing factor administration: Is CRF a mediator of anxiety or stress responses?","volume":"15","author":"Dunn","year":"1990","journal-title":"Brain Res. Brain Res. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jcmgh.2024.01.024","article-title":"Advances in Brain-Gut-Microbiome Interactions: A Comprehensive Update on Signaling Mechanisms, Disorders, and Therapeutic Implications","volume":"18","author":"Dong","year":"2024","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e26867","DOI":"10.2196\/26867","article-title":"Medical Insights from Posts About Irritable Bowel Syndrome by Adolescent Patients and Their Parents: Topic Modeling and Social Network Analysis","volume":"23","author":"Zhong","year":"2021","journal-title":"J. Med. Internet Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kazunori, K., Yasumasa, I., and Makoto, D. (2021). Hypothalamic Regulation of Corticotropin-Releasing Factor under Stress and Stress Resilience. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212242"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3389\/fnins.2014.00052","article-title":"CRF and urocortin peptides as modulators of energy balance and feeding behavior during stress","volume":"8","author":"Stengel","year":"2014","journal-title":"Front. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1007\/s10620-020-06109-5","article-title":"Microbiome and Its Role in Irritable Bowel Syndrome","volume":"65","author":"Pimentel","year":"2020","journal-title":"Dig. Dis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e13378","DOI":"10.1111\/nmo.13378","article-title":"Systemic cytokines are elevated in a subset of patients with irritable bowel syndrome but largely unrelated to symptom characteristics","volume":"30","author":"Bennet","year":"2018","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.cyto.2017.05.005","article-title":"Inflammatory cytokines and oxidative stress biomarkers in irritable bowel syndrome: Association with digestive symptoms and quality of life","volume":"93","author":"Choghakhori","year":"2017","journal-title":"Cytokine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1053\/j.gastro.2007.01.046","article-title":"Immune activation in patients with irritable bowel syndrome","volume":"132","author":"Liebregts","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s12016-019-08740-1","article-title":"The Innate Part of the Adaptive Immune System","volume":"58","author":"Hillion","year":"2020","journal-title":"Clinic Rev. Allerg. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.jaci.2009.12.980","article-title":"Overview of the immune response","volume":"125","author":"Chaplin","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101780","DOI":"10.1016\/j.xcrm.2024.101780","article-title":"Mast cell modulation: A novel therapeutic strategy for abdominal pain in irritable bowel syndrome","volume":"5","author":"Remoortel","year":"2024","journal-title":"Cell Rep. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"106547","DOI":"10.1016\/j.phrs.2022.106547","article-title":"Tantali fibromyalgic supplicium: Is there any relief with the antidepressant employment? A systematic review","volume":"186","author":"Ilari","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s40199-019-00284-1","article-title":"Natural polyphenols for the prevention of irritable bowel syndrome: Molecular mechanisms and targets; a comprehensive review","volume":"27","author":"Roudsari","year":"2019","journal-title":"DARU J. Pharm. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Plamada, D., and Vodnar, D.C. (2021). Polyphenols\u2014Gut Microbiota Interrelationship: A Transition to a New Generation of Prebiotics. Nutrients, 14.","DOI":"10.3390\/nu14010137"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.phrs.2016.07.043","article-title":"Pharmacological effect of a new idebenone formulation in a model of carrageenan-induced inflammatory pain","volume":"111","author":"Lauro","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e0156039","DOI":"10.1371\/journal.pone.0156039","article-title":"Inhibition of Spinal Oxidative Stress by Bergamot Polyphenolic Fraction Attenuates the Development of Morphine Induced Tolerance and Hyperalgesia in Mice","volume":"11","author":"Lauro","year":"2016","journal-title":"PLoS ONE"},{"key":"ref_42","first-page":"105","article-title":"Olea Europea-derived phenolic products attenuate antinociceptive morphine tolerance: An innovative strategic approach to treat cancer pain","volume":"28","author":"Muscoli","year":"2014","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ilari, S., Lauro, F., Giancotti, L.A., Malafoglia, V., Dagostino, C., Gliozzi, M., Condemi, A., Maiuolo, J., Oppedisano, F., and Palma, E. (2021). The Protective Effect of Bergamot Polyphenolic Fraction (BPF) on Chemotherapy-Induced Neuropathic Pain. Pharmaceuticals, 14.","DOI":"10.3390\/ph14100975"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1002\/ptr.6419","article-title":"Polyphenols: A concise overview on the chemistry, occurrence, and human health","volume":"33","author":"Durazzo","year":"2019","journal-title":"Phytother. Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Agnieszka, M., Jurek, J., Owczarek, M., Guerrera, I., Torrisi, S.A., Castellano, S., Grosso, G., Alshatwi, A., and Godos, J. (2023). Polyphenol-Rich Beverages and Mental Health Outcomes. Antioxidants, 12.","DOI":"10.3390\/antiox12020272"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"76548","DOI":"10.3389\/fpsyt.2021.765485","article-title":"Effects of Polyphenol Supplementations on Improving Depression, Anxiety, and Quality of Life in Patients With Depression","volume":"12","author":"Lin","year":"2021","journal-title":"Front. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/jhn.12582","article-title":"A systematic literature review of the effect of anthocyanins on gut microbiota populations","volume":"32","author":"Igwe","year":"2019","journal-title":"J. Human. Nutr. Diet."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Maiuolo, J., Gliozzi, M., Carresi, C., Musolino, V., Oppedisano, F., Scarano, F., Nucera, S., Scicchitano, M., Bosco, F., and Macri, R. (2021). Nutraceuticals and Cancer: Potential for Natural Polyphenols. Nutrients, 13.","DOI":"10.3390\/nu13113834"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Laurindo, L.F., Santos, A.R.D.O.D., Carvalho, A.C.A.D., Bechara, M.D., Guiguer, E.L., Goulart, R.D.A., Vargas Sinatora, R., Ara\u00fajo, A.C., and Barbalho, S.M. (2023). Phytochemicals and Regulation of NF-kB in Inflammatory Bowel Diseases: An Overview of In Vitro and In Vivo Effects. Metabolites, 13.","DOI":"10.3390\/metabo13010096"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Chiu, H.F., Venkatakrishnan, K., Golovinskaia, O., and Wang, C.K. (2021). Gastroprotective Effects of Polyphenols against Various Gastro-Intestinal Disorders: A Mini-Review with Special Focus on Clinical Evidence. Molecules, 26.","DOI":"10.3390\/molecules26072090"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"631","DOI":"10.3389\/fphar.2018.00631","article-title":"trans-Resveratrol Ameliorates Stress-Induced Irritable Bowel Syndrome-Like Behaviors by Regulation of Brain-Gut Axis","volume":"9","author":"Xu","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Zorzi, M., Gai, F., Medana, C., Aigotti, R., Morello, S., and Peiretti, P.G. (2020). Bioactive Compounds and Antioxidant Capacity of Small Berries. Foods, 9.","DOI":"10.3390\/foods9050623"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/nyas.13426","article-title":"Resveratrol and inflammatory bowel disease","volume":"1403","author":"Shi","year":"2017","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"275","DOI":"10.15403\/jgld.2014.1121.243.sst","article-title":"A Pilot Study of the Effect of Aloe barbadensis Mill. Extract (AVH200\u00ae) in Patients with Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study","volume":"24","year":"2015","journal-title":"J. Gastrointestin Liver Dis."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Chiarioni, G., Popa, S.L., Ismaiel, A., Pop, C., Dumitrascu, D.I., Brata, V.D., Duse, T.A., Incze, V., and Surdea-Blaga, T. (2023). The Effect of Polyphenols, Minerals, Fibers, and Fruits on Irritable Bowel Syndrome: A Systematic Review. Nutrients, 15.","DOI":"10.3390\/nu15184070"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ng, Q.X., Soh, A.Y.S., Loke, W., Venkatanarayanan, N., Lim, D.Y., and Yeo, W.S. (2018). A Meta-Analysis of the Clinical Use of Curcumin for Irritable Bowel Syndrome (IBS). J. Clin. Med., 7.","DOI":"10.3390\/jcm7100298"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Burillo, S., Navajas-Porras, B., L\u00f3pez-Maldonado, A., Hinojosa-Nogueira, D., Pastoriza, S., and Rufi\u00e1n-Henares, J.\u00c1. (2021). Green Tea and Its Relation to Human Gut Microbiome. Molecules, 26.","DOI":"10.3390\/molecules26133907"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s10787-015-0236-1","article-title":"Green tea polyphenols and their potential role in health and disease","volume":"23","author":"Afzal","year":"2015","journal-title":"Inflammopharmacology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1089\/jmf.2018.4264","article-title":"Quercetin Attenuates Visceral Hypersensitivity and 5-Hydroxytryptamine Availability in Postinflammatory Irritable Bowel Syndrome Rats: Role of Enterochromaffin Cells in the Colon","volume":"22","author":"Qin","year":"2019","journal-title":"J. Med. Food."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.cbi.2010.08.007","article-title":"Anti-inflammatory effects of dietary phenolic compounds in an in vitro model of inflamed human intestinal epithelium","volume":"188","author":"Sergent","year":"2010","journal-title":"Chem. Biol. Interact."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"14126","DOI":"10.3748\/wjg.v20.i39.14126","article-title":"Impact of psychological stress on irritable bowel syndrome","volume":"20","author":"Qin","year":"2014","journal-title":"WJG"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1586\/17474124.2015.1002086","article-title":"Dietary anthocyanins as a complementary medicinal approach for management of inflammatory bowel disease","volume":"9","author":"Sodagari","year":"2015","journal-title":"Expert. Rev. Gastroenterol. Hepatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ijbiomac.2022.03.118","article-title":"ROS-responsive thioketal-linked alginate\/chitosan carriers for irritable bowel syndrome with diarrhea therapy","volume":"209","author":"Zhang","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"666-e278","DOI":"10.1111\/j.1365-2982.2011.01697.x","article-title":"Role of neuronal nitric oxide synthase in colonic distension-induced hyperalgesia in distal colon of neonatal maternal separated male rats: Elevated nNOS expression from distal colon of NMS rats","volume":"23","author":"Tjong","year":"2011","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/s41575-018-0021-x","article-title":"Mitochondrial function\u2014gatekeeper of intestinal epithelial cell homeostasis","volume":"15","author":"Rath","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"629026","DOI":"10.3389\/fphar.2020.629026","article-title":"Pharmacological Therapies and Their Clinical Targets in Irritable Bowel Syndrome With Diarrhea","volume":"11","author":"Colomier","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e15920","DOI":"10.1097\/MD.0000000000015920","article-title":"Pharmacological treatments for patients with irritable bowel syndrome: An umbrella review of systematic reviews and meta-analyses","volume":"98","author":"Qin","year":"2019","journal-title":"Medicine"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1136\/gutjnl-2015-309957","article-title":"High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome","volume":"65","author":"Pellegrini","year":"2016","journal-title":"Gut"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1136\/gutjnl-2015-309460","article-title":"Psychological comorbidity increases the risk for postinfectious IBS partly by enhanced susceptibility to develop infectious gastroenteritis","volume":"65","author":"Wouters","year":"2016","journal-title":"Gut"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1111\/j.1365-2036.2005.02685.x","article-title":"Gabapentin reduces rectal mechanosensitivity and increases rectal compliance in patients with diarrhoea-predominant irritable bowel syndrome","volume":"22","author":"Lee","year":"2005","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"463","DOI":"10.15403\/jgld-229","article-title":"Mast Cells in Irritable Bowel Syndrome: A Systematic Review","volume":"28","author":"Krammer","year":"2019","journal-title":"JGLD"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.3748\/wjg.15.1548","article-title":"Efficacy of tricyclic antidepressants in irritable bowel syndrome: A meta-analysis","volume":"15","author":"Rahimi","year":"2009","journal-title":"WJG"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e0127815","DOI":"10.1371\/journal.pone.0127815","article-title":"Efficacy and Safety of Antidepressants for the Treatment of Irritable Bowel Syndrome: A Meta-Analysis","volume":"10","author":"Xie","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.cgh.2008.02.060","article-title":"Prospective Study of Motor, Sensory, Psychologic, and Autonomic Functions in Patients With Irritable Bowel Syndrome","volume":"6","author":"Camilleri","year":"2008","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"G701","DOI":"10.1152\/ajpgi.00186.2018","article-title":"Mucosal RNA and protein expression as the next frontier in IBS: Abnormal function despite morphologically intact small intestinal mucosa","volume":"316","author":"Santos","year":"2019","journal-title":"Am. J. Physiol. -Gastrointest. Liver Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/gutjnl-2012-303857","article-title":"Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia","volume":"63","author":"Vanheel","year":"2014","journal-title":"Gut"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/ajg.2015.158","article-title":"Evidence for neuronal and structural changes in submucous ganglia of patients with functional dyspepsia","volume":"110","author":"Cirillo","year":"2015","journal-title":"Am. J. Gastroenterol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4012","DOI":"10.3748\/wjg.v18.i30.4012","article-title":"Clinical trial: Lactobacillus plantarum 299v (DSM 9843) improves symptoms of irritable bowel syndrome","volume":"18","year":"2012","journal-title":"WJG"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1097\/MEG.0000000000001737","article-title":"Clinical efficacy and safety of ketotifen in treating irritable bowel syndrome with diarrhea","volume":"32","author":"Wang","year":"2020","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e13718","DOI":"10.1111\/nmo.13718","article-title":"Mast cells are increased in the small intestinal mucosa of patients with irritable bowel syndrome: A systematic review and meta-analysis","volume":"31","author":"Robles","year":"2019","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"15","DOI":"10.51821\/87.1.12487","article-title":"Efficacy of mast cell directed therapies in irritable bowel syndrome: A systematic review","volume":"87","author":"Coppens","year":"2024","journal-title":"AGEB"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Ng, Q.X., Yau, C.E., Yaow, C.Y.L., Chong, R.I.H., Chong, N.Z.-Y., Teoh, S.E., Lim, Y.L., Soh, A.Y.S., Ng, W.K., and Thumboo, J. (2023). What Has Longitudinal \u2018Omics\u2019 Studies Taught Us about Irritable Bowel Syndrome? A Systematic Review. Metabolites, 13.","DOI":"10.3390\/metabo13040484"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1097\/MPG.0000000000001904","article-title":"Eosinophil Counts in the Small Intestine and Colon of Children Without Apparent Gastrointestinal Disease: A Meta-analysis","volume":"67","author":"Kiss","year":"2018","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.1365-2036.2009.04041.x","article-title":"Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: A randomized controlled proof-of-concept study","volume":"30","author":"Corinaldesi","year":"2009","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1053\/j.gastro.2018.07.011","article-title":"Rome Foundation Working Team Report on Post-Infection Irritable Bowel Syndrome","volume":"156","author":"Barbara","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"268S","DOI":"10.1093\/ajcn\/81.1.268S","article-title":"Health promotion by flavonoids, tocopherols, tocotrienols, and other phenols: Direct or indirect effects? Antioxidant or not?","volume":"81","author":"Halliwell","year":"2005","journal-title":"Am. J. Clin. 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