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      Vitamin D and colorectal cancer: Chemopreventive perspectives through the gut microbiota and the immune system

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          Abstract

          Vitamin D and its receptor are involved in health and diseases through multiple mechanisms including the immune system and gut microbiota modulations. Gut microbiota variations have huge implications in intestinal and extra‐intestinal disorders such as colorectal cancer (CRC). This review highlights the preventive role of vitamin D in colorectal tumorigenesis through the effects on the immune system and gut microbiota modulation. The different associations between vitamin D, gut microbial homeostasis, immune system, and CRC, are dissected. Vitamin D is supposed to exert several chemopreventive effects on CRC including direct antineoplastic mechanisms, the effects on the immune system, and gut microbiota modulation. Large clinical studies with a randomized design, are required to confirm the role of vitamin D in CRC, confirming its key role in the complex interplay between the gut immune system and microbiota.

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          What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases

          Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions.
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            Introduction to the human gut microbiota

            The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host during homeostasis and disease. Multiple factors contribute to the establishment of the human gut microbiota during infancy. Diet is considered as one of the main drivers in shaping the gut microbiota across the life time. Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens. Altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections. The interpretation of these studies relies on a better understanding of inter-individual variations, heterogeneity of bacterial communities along and across the GI tract, functional redundancy and the need to distinguish cause from effect in states of dysbiosis. This review summarises our current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host–microbe interactions.
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              Vitamin D Deficiency

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                Author and article information

                Contributors
                emanuele.rinninella@unicatt.it
                Journal
                Biofactors
                Biofactors
                10.1002/(ISSN)1872-8081
                BIOF
                Biofactors (Oxford, England)
                John Wiley & Sons, Inc. (Hoboken, USA )
                0951-6433
                1872-8081
                24 September 2021
                Mar-Apr 2022
                : 48
                : 2 ( doiID: 10.1002/biof.v48.2 )
                : 285-293
                Affiliations
                [ 1 ] UOC di Nutrizione Clinica, Dipartimento di Scienze Mediche e Chirurgiche Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy
                [ 2 ] Dipartimento di Medicina e Chirurgia Traslazionale Università Cattolica Del Sacro Cuore Rome Italy
                [ 3 ] UOSD di Nutrizione Avanzata in Oncologia, Dipartimento di Scienze Mediche e Chirurgiche Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy
                [ 4 ] Scuola di Specializzazione in Scienza dell'Alimentazione Università di Roma Tor Vergata Rome Italy
                [ 5 ] UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy
                Author notes
                [*] [* ] Correspondence

                UOC di Nutrizione Clinica, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy.

                Email: emanuele.rinninella@ 123456unicatt.it

                Author information
                https://orcid.org/0000-0002-9165-2367
                Article
                BIOF1786
                10.1002/biof.1786
                9293134
                34559412
                eb7ad664-6ba6-42cf-8e3d-67ba04a86f4d
                © 2021 The Authors. BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 31 August 2021
                : 13 September 2021
                Page count
                Figures: 2, Tables: 0, Pages: 9, Words: 7335
                Categories
                Review Article
                Mini Theme issue on “Polyphenols‐Microbiota Interactions”
                Guest editors: Giovanni Scapagnini and Emanuele Rinninella
                Review Articles
                Custom metadata
                2.0
                March/April 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.7 mode:remove_FC converted:18.07.2022

                Molecular biology
                colorectal cancer,gut microbiota,immune system,inflammation,vitamin d
                Molecular biology
                colorectal cancer, gut microbiota, immune system, inflammation, vitamin d

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