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      Prebiotics, Bone and Mineral Metabolism

      review-article
      ,
      Calcified Tissue International
      Springer US
      Prebiotic, Fiber, Calcium, Bone, Osteoporosis, Microbiome

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          Abstract

          Increasing interest in functional foods has driven discovery in the area of bioactive compounds. Prebiotics are non-digestible carbohydrate compounds that, when consumed, elicit health benefits and aid in the prevention and treatment of chronic diseases. While prebiotics have been shown to improve a number of chronic, inflammatory conditions, growing evidence exists for prebiotic effects on calcium metabolism and bone health. These novel dietary fibers have been shown to increase calcium absorption in the lower intestines of both preclinical and human models. Rodent models have also been imperative for understanding prebiotic effects on bone mineral density and measures of skeletal strength. Although fewer data are available for humans, bone-related prebiotic effects exist across the lifecycle, suggesting benefits for attainment of peak bone mass during adolescence and minimized bone resorption among postmenopausal women. These effects are thought to occur through prebiotic–microbe interactions in the large intestine. Current prebiotic mechanisms for improved mineral absorption and skeletal health include alterations in gut microbiota composition, production of short-chain fatty acids, altered intestinal pH, biomarker modification, and immune system regulation. While the majority of available data support improved mineral bioavailability, emerging evidence suggests alternate microbial roles and the presence of an intricate gut–bone signaling axis. Overall, the current scientific literature supports prebiotic consumption as a cost-effective and sustainable approach for improved skeletal health and/or fracture prevention. The goal of this review is to discuss both foundational and recent research in the area of prebiotics, mineral metabolism, and bone health.

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          Most cited references102

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          The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon.

          The microbiome is being characterized by large-scale sequencing efforts, yet it is not known whether it regulates host metabolism in a general versus tissue-specific manner or which bacterial metabolites are important. Here, we demonstrate that microbiota have a strong effect on energy homeostasis in the colon compared to other tissues. This tissue specificity is due to colonocytes utilizing bacterially produced butyrate as their primary energy source. Colonocytes from germfree mice are in an energy-deprived state and exhibit decreased expression of enzymes that catalyze key steps in intermediary metabolism including the TCA cycle. Consequently, there is a marked decrease in NADH/NAD(+), oxidative phosphorylation, and ATP levels, which results in AMPK activation, p27(kip1) phosphorylation, and autophagy. When butyrate is added to germfree colonocytes, it rescues their deficit in mitochondrial respiration and prevents them from undergoing autophagy. The mechanism is due to butyrate acting as an energy source rather than as an HDAC inhibitor. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Interactions between commensal intestinal bacteria and the immune system.

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              Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum.

              Loss- and gain-of-function mutations in the broadly expressed gene Lrp5 affect bone formation, causing osteoporosis and high bone mass, respectively. Although Lrp5 is viewed as a Wnt coreceptor, osteoblast-specific disruption of beta-Catenin does not affect bone formation. Instead, we show here that Lrp5 inhibits expression of Tph1, the rate-limiting biosynthetic enzyme for serotonin in enterochromaffin cells of the duodenum. Accordingly, decreasing serotonin blood levels normalizes bone formation and bone mass in Lrp5-deficient mice, and gut- but not osteoblast-specific Lrp5 inactivation decreases bone formation in a beta-Catenin-independent manner. Moreover, gut-specific activation of Lrp5, or inactivation of Tph1, increases bone mass and prevents ovariectomy-induced bone loss. Serotonin acts on osteoblasts through the Htr1b receptor and CREB to inhibit their proliferation. By identifying duodenum-derived serotonin as a hormone inhibiting bone formation in an Lrp5-dependent manner, this study broadens our understanding of bone remodeling and suggests potential therapies to increase bone mass.
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                Author and article information

                Contributors
                602-827-2261 , cwhisner@asu.edu
                Journal
                Calcif Tissue Int
                Calcif. Tissue Int
                Calcified Tissue International
                Springer US (New York )
                0171-967X
                1432-0827
                27 October 2017
                27 October 2017
                2018
                : 102
                : 4
                : 443-479
                Affiliations
                ISNI 0000 0001 2151 2636, GRID grid.215654.1, School of Nutrition & Health Promotion, , Arizona State University, ; 500 North 5th Street, Phoenix, AZ 85004 USA
                Article
                339
                10.1007/s00223-017-0339-3
                5851694
                29079996
                852b8b61-3960-4c42-ae77-50450f06952f
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 31 July 2017
                : 3 October 2017
                Categories
                Review
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2018

                Human biology
                prebiotic,fiber,calcium,bone,osteoporosis,microbiome
                Human biology
                prebiotic, fiber, calcium, bone, osteoporosis, microbiome

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