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      The Functional Role of Lactoferrin in Intestine Mucosal Immune System and Inflammatory Bowel Disease

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          Abstract

          Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), is one of the main types of intestinal inflammatory diseases with intestine mucosal immune disorder. Intestine mucosal immune system plays a remarkable and important role in the etiology and pathogenesis of IBD. Therefore, understanding the intestine mucosal immune mechanism is a key step to develop therapeutic interventions for IBD. Intestine mucosal immune system and IBD are influenced by various factors, such as inflammation, gut permeability, gut microbiota, and nutrients. Among these factors, emerging evidence show that nutrients play a key role in inflammation activation, integrity of intestinal barrier, and immune cell modulation. Lactoferrin (LF), an iron-binding glycoprotein belonging to transferrin family, is a dietary bioactive component abundantly found in mammalian milk. Notably, LF has been reported to perform diverse biological functions including antibacterial activity, anti-inflammatory activity, intestinal barrier protection, and immune cell modulation, and is involved in maintaining intestine mucosal immune homeostasis. The improved understanding of the properties of LF in intestine mucosal immune system and IBD will facilitate its application in nutrition, clinical medicine, and health. Herein, this review outlines the recent advancements on LF as a potential therapeutic intervention for IBD associated with intestine mucosal immune system dysfunction. We hope this review will provide a reference for future studies and lay a theoretical foundation for LF-based therapeutic interventions for IBD by understanding the particular effects of LF on intestine mucosal immune system.

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          Most cited references146

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          Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies.

          Inflammatory bowel disease is a global disease in the 21st century. We aimed to assess the changing incidence and prevalence of inflammatory bowel disease around the world.
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            Role of the microbiota in immunity and inflammation.

            The microbiota plays a fundamental role on the induction, training, and function of the host immune system. In return, the immune system has largely evolved as a means to maintain the symbiotic relationship of the host with these highly diverse and evolving microbes. When operating optimally, this immune system-microbiota alliance allows the induction of protective responses to pathogens and the maintenance of regulatory pathways involved in the maintenance of tolerance to innocuous antigens. However, in high-income countries, overuse of antibiotics, changes in diet, and elimination of constitutive partners, such as nematodes, may have selected for a microbiota that lack the resilience and diversity required to establish balanced immune responses. This phenomenon is proposed to account for some of the dramatic rise in autoimmune and inflammatory disorders in parts of the world where our symbiotic relationship with the microbiota has been the most affected. Copyright © 2014 Elsevier Inc. All rights reserved.
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              Interaction between microbiota and immunity in health and disease

              The interplay between the commensal microbiota and the mammalian immune system development and function includes multifold interactions in homeostasis and disease. The microbiome plays critical roles in the training and development of major components of the host’s innate and adaptive immune system, while the immune system orchestrates the maintenance of key features of host-microbe symbiosis. In a genetically susceptible host, imbalances in microbiota-immunity interactions under defined environmental contexts are believed to contribute to the pathogenesis of a multitude of immune-mediated disorders. Here, we review features of microbiome-immunity crosstalk and their roles in health and disease, while providing examples of molecular mechanisms orchestrating these interactions in the intestine and extra-intestinal organs. We highlight aspects of the current knowledge, challenges and limitations in achieving causal understanding of host immune-microbiome interactions, as well as their impact on immune-mediated diseases, and discuss how these insights may translate towards future development of microbiome-targeted therapeutic interventions.
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                Author and article information

                Contributors
                Journal
                Front Nutr
                Front Nutr
                Front. Nutr.
                Frontiers in Nutrition
                Frontiers Media S.A.
                2296-861X
                25 November 2021
                2021
                : 8
                : 759507
                Affiliations
                [1] 1Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, China Agricultural University , Beijing, China
                [2] 2Key Laboratory of Functional Dairy, Ministry of Education, Department of Nutrition and Health, China Agricultural University , Beijing, China
                [3] 3Inner Mongolia Yili Industrial Group, Co., Ltd. , Hohhot, China
                [4] 4Yili Maternal & Infant Nutrition Institute , Beijing, China
                [5] 5Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen , Groningen, Netherlands
                [6] 6Department of Genetics, University of Groningen and University Medical Center Groningen , Groningen, Netherlands
                [7] 7College of Food Science and Engineering, Gansu Agricultural University , Lanzhou, China
                Author notes

                Edited by: Xian Wu, Miami University, United States

                Reviewed by: Maria Elisa Drago-Serrano, Universidad Autónoma Metropolitana Unidad Xochimilco, Mexico; Xiaoqiong Cao, University of Massachusetts Amherst, United States

                *Correspondence: Yixuan Li liyixuan9735@ 123456126.com

                This article was submitted to Nutritional Immunology, a section of the journal Frontiers in Nutrition

                Article
                10.3389/fnut.2021.759507
                8655231
                34901112
                0ab67cbf-cf2d-4624-b2d5-be9891e865f7
                Copyright © 2021 Liu, Feng, Zhang, Hu, Sun, Sun, Sun, Wang, Zhang, Wang and Li.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 August 2021
                : 18 October 2021
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 146, Pages: 13, Words: 10213
                Funding
                Funded by: National Natural Science Foundation of China-China Academy of General Technology Joint Fund for Basic Research, doi 10.13039/501100019492;
                Award ID: 31625025
                Award ID: 32000082
                Funded by: National Key Laboratory of Animal Nutrition, doi 10.13039/501100011364;
                Award ID: 2004DA125184F1909
                Funded by: Higher Education Discipline Innovation Project, doi 10.13039/501100013314;
                Categories
                Nutrition
                Review

                cytokine,intestinal epithelial cells,immunocytes,lactoferrin,inflammatory bowel disease,intestine mucosal immune system

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