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      The Osteoporosis/Microbiota Linkage: The Role of miRNA

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          Abstract

          Hundreds of trillions of bacteria are present in the human body in a mutually beneficial symbiotic relationship with the host. A stable dynamic equilibrium exists in healthy individuals between the microbiota, host organism, and environment. Imbalances of the intestinal microbiota contribute to the determinism of various diseases. Recent research suggests that the microbiota is also involved in the regulation of the bone metabolism, and its alteration may induce osteoporosis. Due to modern molecular biotechnology, various mechanisms regulating the relationship between bone and microbiota are emerging. Understanding the role of microbiota imbalances in the development of osteoporosis is essential for the development of potential osteoporosis prevention and treatment strategies through microbiota targeting. A relevant complementary mechanism could be also constituted by the permanent relationships occurring between microbiota and microRNAs (miRNAs). miRNAs are a set of small non-coding RNAs able to regulate gene expression. In this review, we recapitulate the physiological and pathological meanings of the microbiota on osteoporosis onset by governing miRNA production. An improved comprehension of the relations between microbiota and miRNAs could furnish novel markers for the identification and monitoring of osteoporosis, and this appears to be an encouraging method for antagomir-guided tactics as therapeutic agents.

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          Most cited references133

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          The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.

          Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota-derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
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            The microbiome and innate immunity.

            The intestinal microbiome is a signalling hub that integrates environmental inputs, such as diet, with genetic and immune signals to affect the host's metabolism, immunity and response to infection. The haematopoietic and non-haematopoietic cells of the innate immune system are located strategically at the host-microbiome interface. These cells have the ability to sense microorganisms or their metabolic products and to translate the signals into host physiological responses and the regulation of microbial ecology. Aberrations in the communication between the innate immune system and the gut microbiota might contribute to complex diseases.
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              Induction of colonic regulatory T cells by indigenous Clostridium species.

              CD4(+) T regulatory cells (T(regs)), which express the Foxp3 transcription factor, play a critical role in the maintenance of immune homeostasis. Here, we show that in mice, T(regs) were most abundant in the colonic mucosa. The spore-forming component of indigenous intestinal microbiota, particularly clusters IV and XIVa of the genus Clostridium, promoted T(reg) cell accumulation. Colonization of mice by a defined mix of Clostridium strains provided an environment rich in transforming growth factor-β and affected Foxp3(+) T(reg) number and function in the colon. Oral inoculation of Clostridium during the early life of conventionally reared mice resulted in resistance to colitis and systemic immunoglobulin E responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                24 November 2020
                December 2020
                : 21
                : 23
                : 8887
                Affiliations
                [1 ]Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; lia.ginaldi@ 123456cc.univaq.it (L.G.); maddalena.sirufo@ 123456gmail.com (M.M.S.)
                [2 ]Allergy and Clinical Immunology Unit, Center for the Diagnosis and Treatment of Osteoporosis, AUSL 04 Teramo, 64100 Teramo, Italy
                [3 ]Division of Hematology, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, 98125 Messina, Italy; aallegra@ 123456unime.it
                [4 ]Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), 98164 Messina, Italy; giovanni.pioggia@ 123456cnr.it
                [5 ]Clinical Physiology Institute, National Research Council of Italy (IFC-CNR), 56124 Pisa, Italy; atonacci@ 123456ifc.cnr.it
                [6 ]School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; gangemis@ 123456unime.it
                Author notes
                [* ]Correspondence: demartinis@ 123456cc.univaq.it ; Tel.: +39-0861-429862
                Author information
                https://orcid.org/0000-0003-4253-1312
                https://orcid.org/0000-0001-6156-8239
                https://orcid.org/0000-0002-8089-7449
                https://orcid.org/0000-0001-8335-5541
                Article
                ijms-21-08887
                10.3390/ijms21238887
                7727697
                33255179
                87b05d7d-1e76-490c-8468-006ce21e8275
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 27 October 2020
                : 23 November 2020
                Categories
                Review

                Molecular biology
                osteoporosis,microbiota,microrna,bone metabolism,gene expression,osteoblast,diet
                Molecular biology
                osteoporosis, microbiota, microrna, bone metabolism, gene expression, osteoblast, diet

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