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      Dual Role of Indoles Derived From Intestinal Microbiota on Human Health

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          Abstract

          Endogenous indole and its derivatives (indoles), considered as promising N-substituted heterocyclic compounds, are tryptophan metabolites derived from intestinal microbiota and exhibit a range of biological activities. Recent studies indicate that indoles contribute to maintaining the biological barrier of the human intestine, which exert the anti-inflammatory activities mainly through activating AhR and PXR receptors to affect the immune system’s function, significantly improving intestinal health (inflammatory bowel disease, hemorrhagic colitis, colorectal cancer) and further promote human health (diabetes mellitus, central system inflammation, and vascular regulation). However, the revealed toxic influences cannot be ignored. Indoxyl sulfate, an indole derivative, performs nephrotoxicity and cardiovascular toxicity. We addressed the interaction between indoles and intestinal microbiota and the indoles’ effects on human health as double-edged swords. This review provides scientific bases for the correlation of indoles with diseases moreover highlights several directions for subsequent indoles-related studies.

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          Most cited references158

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          Neutrophil recruitment and function in health and inflammation.

          Neutrophils have traditionally been thought of as simple foot soldiers of the innate immune system with a restricted set of pro-inflammatory functions. More recently, it has become apparent that neutrophils are, in fact, complex cells capable of a vast array of specialized functions. Although neutrophils are undoubtedly major effectors of acute inflammation, several lines of evidence indicate that they also contribute to chronic inflammatory conditions and adaptive immune responses. Here, we discuss the key features of the life of a neutrophil, from its release from bone marrow to its death. We discuss the possible existence of different neutrophil subsets and their putative anti-inflammatory roles. We focus on how neutrophils are recruited to infected or injured tissues and describe differences in neutrophil recruitment between different tissues. Finally, we explain the mechanisms that are used by neutrophils to promote protective or pathological immune responses at different sites.
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            Gut microbiota, metabolites and host immunity.

            The microbiota - the collection of microorganisms that live within and on all mammals - provides crucial signals for the development and function of the immune system. Increased availability of technologies that profile microbial communities is facilitating the entry of many immunologists into the evolving field of host-microbiota studies. The microbial communities, their metabolites and components are not only necessary for immune homeostasis, they also influence the susceptibility of the host to many immune-mediated diseases and disorders. In this Review, we discuss technological and computational approaches for investigating the microbiome, as well as recent advances in our understanding of host immunity and microbial mutualism with a focus on specific microbial metabolites, bacterial components and the immune system.
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              Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease

              The gut microbiota is a crucial actor in human physiology. Many of these effects are mediated by metabolites that are either produced by the microbes or derived from the transformation of environmental or host molecules. Among the array of metabolites at the interface between these microorganisms and the host is the essential aromatic amino acid tryptophan (Trp). In the gut, the three major Trp metabolism pathways leading to serotonin (5-hydroxytryptamine), kynurenine (Kyn), and indole derivatives are under the direct or indirect control of the microbiota. In this review, we gather the most recent advances concerning the central role of Trp metabolism in microbiota-host crosstalk in health and disease. Deciphering the complex equilibrium between these pathways will facilitate a better understanding of the pathogenesis of human diseases and open therapeutic opportunities.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                17 June 2022
                2022
                : 13
                : 903526
                Affiliations
                [1] 1 State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University , Hangzhou, China
                [2] 2 Department of Basic Medical Sciences, Shulan International Medical College, Zhejiang Shuren University , Hangzhou, China
                [3] 3 Department of Medicine and pharmacy, Ocean University of China , Qingdao, China
                [4] 4 Key Laboratory of Endocrine Gland Diseases of Zhejiang Province , Hangzhou, China
                [5] 5 Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College) , Hangzhou, China
                [6] 6 Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences , Hangzhou, China
                Author notes

                Edited by: Qixiao Zhai, Jiangnan University, China

                Reviewed by: Tingtao Chen, Nanchang University, China; Teresa Zelante, University of Perugia, Italy; Jiachao Zhang, Hainan University, China

                *Correspondence: Lanjuan Li, ljli@ 123456zju.edu.cn ; Wei Liu, biolwei@ 123456sina.com

                †These authors have contributed equally to this work. The author order was determined by their equal but gradated contributions for this paper

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

                Article
                10.3389/fimmu.2022.903526
                9248744
                35784338
                9edece97-ac5b-4a47-9724-7549d88dd0d1
                Copyright © 2022 Ye, Li, Anjum, Zhong, Miao, Zheng, Liu 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
                : 24 March 2022
                : 23 May 2022
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 158, Pages: 15, Words: 7703
                Categories
                Immunology
                Review

                Immunology
                indole,inflammation,intestinal flora,indoxyl sulfate,dual role
                Immunology
                indole, inflammation, intestinal flora, indoxyl sulfate, dual role

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