Lentinula edodes Cultured Extract and Rouxiella badensis subsp. acadiensis (Canan SV-53) Intake Alleviates Immune Deregulation and Inflammation by Modulating Signaling Pathways and Epigenetic Mechanisms
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Published:2023-09-27
Issue:19
Volume:24
Page:14610
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Shahbazi Roghayeh1, Yasavoli-Sharahi Hamed1, Alsadi Nawal1, Sharifzad Farzaneh2, Fang Sandra3, Cuenin Cyrille4, Cahais Vincent4ORCID, Chung Felicia Fei-Lei45ORCID, Herceg Zdenko4ORCID, Matar Chantal16
Affiliation:
1. Cellular and Molecular Medicine Department, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada 2. Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA 3. Translational Molecular Medicine Department, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada 4. Epigenomics and Mechanisms Branch, International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, 69007 Lyon, France 5. Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Jalan Universiti, Bandar Sunway, Subang Jaya 47500, Selangor, Malaysia 6. School of Nutrition, Faculty of Health Sciences, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Abstract
Puberty is a critical developmental period of life characterized by marked physiological changes, including changes in the immune system and gut microbiota development. Exposure to inflammation induced by immune stressors during puberty has been found to stimulate central inflammation and lead to immune disturbance at distant sites from the gut; however, its enduring effects on gut immunity are not well explored. Therefore, in this study, we used a pubertal lipopolysaccharides (LPS)-induced inflammation mouse model to mimic pubertal exposure to inflammation and dysbiosis. We hypothesized that pubertal LPS-induced inflammation may cause long-term dysfunction in gut immunity by enduring dysregulation of inflammatory signaling and epigenetic changes, while prebiotic/probiotic intake may mitigate the gut immune system deregulation later in life. To this end, four-week-old female Balb/c mice were fed prebiotics/probiotics and exposed to LPS in the pubertal window. To better decipher the acute and enduring immunoprotective effects of biotic intake, we addressed the effect of treatment on interleukin (IL)-17 signaling related-cytokines and pathways. In addition, the effect of treatment on gut microbiota and epigenetic alterations, including changes in microRNA (miRNA) expression and DNA methylation, were studied. Our results revealed a significant dysregulation in selected cytokines, proteins, and miRNAs involved in key signaling pathways related to IL-17 production and function, including IL-17A and F, IL-6, IL-1β, transforming growth factor-β (TGF-β), signal transducer and activator of transcription-3 (STAT3), p-STAT3, forkhead box O1 (FOXO1), and miR-145 in the small intestine of adult mice challenged with LPS during puberty. In contrast, dietary interventions mitigated the lasting adverse effects of LPS on gut immune function, partly through epigenetic mechanisms. A DNA methylation analysis demonstrated that enduring changes in gut immunity in adult mice might be linked to differentially methylated genes, including Lpb, Rorc, Runx1, Il17ra, Rac1, Ccl5, and Il10, involved in Th17 cell differentiation and IL-17 production and signaling. In addition, prebiotic administration prevented LPS-induced changes in the gut microbiota in pubertal mice. Together, these results indicate that following a healthy diet rich in prebiotics and probiotics is an optimal strategy for programming immune system function in the critical developmental windows of life and controlling inflammation later in life.
Funder
NSERC Collaborative Research and Development Grant AHCC Research Association, and New Frontiers in Research Fund—Exploration NFRFE admission scholarship by the Faculty of Graduate and Postgraduate Studies at the University of Ottawa Nutrition and Mental Health Doctoral Scholarship by the Nutrition and Mental Health initiative at the Faculty of Health Sciences at the University of Ottawa
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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