Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss

Lucas, Sébastien; Omata, Yasunori; Hofmann, Jörg; Böttcher, Martin; Iljazović, Aida; Sarter, Kerstin; Albrecht, Olivia; Schulz, Oscar; Krishnacoumar, Brenda; Krönke, Gerhard; Herrmann, Martin; Mougiakakos, Dimitrios; Strowig, Till; Schett, Georg; Zaiss, Mario M.

doi:10.1038/s41467-017-02490-4

Cited by 490 publications

(450 citation statements)

References 47 publications

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“…In addition, SCFAs are important secreted microbial metabolites for osteoporosis alleviation. SCFAs increase calcium absorption and transportation, stimulate the biosynthesis of gut‐derived serotonin, and directly inhibit osteoclast differentiation and bone resorption . In this study, 21 OTUs were annotated as SCFA producers, although not all of them increased after TBP treatment.…”

Section: Discussionmentioning

confidence: 99%

Tuna Bone Powder Alleviates Glucocorticoid‐Induced Osteoporosis via Coregulation of the NF‐κB and Wnt/β‐Catenin Signaling Pathways and Modulation of Gut Microbiota Composition and Metabolism

Yang

et al. 2020

Molecular Nutrition Food Res

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Scope The effects and mechanism of tuna bone powder (TBP) on glucocorticoid‐induced osteoporosis (GIOP) alleviation in terms of signaling pathway coregulation and gut microbiota modulation are investigated. Methods and results The powder size distribution and composition of TBP are measured. The GIOP female mice induced by dexamethasone intramuscular injection are used to examine the anti‐osteoporosis effects of TBP in a 10 week experiment, and improved bone mineral density and bone microarchitecture are observed via micro‐CT. In addition, qRT‐PCR results show that the NF‐κB pathway is inhibited to reduce bone resorption, whereas the Wnt/β‐catenin pathway is activated to enhance bone formation after treatment. Moreover, TBP treatments suppress the release of pro‐inflammatory cytokines, repair dysfunction of the intestinal epithelial barrier, and prevent aggravated systemic inflammation in mRNA levels. Additionally, 16S rRNA gene sequencing indicate that TBP treatments enhance the abundance of anti‐inflammatory bacteria and short‐chain fatty acid (SCFA) producers, which is consistent with increased SCFA contents in feces measured via GC–MS. Conclusion These data show that TBP ameliorates GIOP in mice through four aspects, including coregulating signaling pathways, blocking proinflammatory cytokines, repairing the intestinal epithelial barrier, and modulating gut microbiota. Therefore, TBP may be a potential prebiotic agent to alleviate osteoporosis in humans.

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Section: Discussionmentioning

confidence: 99%

Tuna Bone Powder Alleviates Glucocorticoid‐Induced Osteoporosis via Coregulation of the NF‐κB and Wnt/β‐Catenin Signaling Pathways and Modulation of Gut Microbiota Composition and Metabolism

Yang

et al. 2020

Molecular Nutrition Food Res

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“…Directly, SCFAs bind to receptors (GPR18, GPR41, GPR43, GPR109A) present on osteoclast precursors; in specific, acetate and propionate show higher affinity for GPR41, while butyrate exerts effects mostly via GPR43 activation . Indirectly, SCFAs regulate bone mineral absorption by influencing signalling pathways and gene expression. Butyrate and propionate induce metabolic reprogramming of osteoclasts to enhance glycolysis and thus downregulating critical genes in osteoclasts such as TRAF6 and NFATc1 .…”

Section: Modulation Of Fatty Acids On Specific Bone Cell Typesmentioning

confidence: 99%

Therapeutic potentials and modulatory mechanisms of fatty acids in bone

et al. 2019

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Bone metabolism is a lifelong process that includes bone formation and resorption. Osteoblasts and osteoclasts are the predominant cell types associated with bone metabolism, which is facilitated by other cells such as bone marrow mesenchymal stem cells (BMMSCs), osteocytes and chondrocytes. As an important component in our daily diet, fatty acids are mainly categorized as long‐chain fatty acids including polyunsaturated fatty acids (LCPUFAs), monounsaturated fatty acids (LCMUFAs), saturated fatty acids (LCSFAs), medium‐/short‐chain fatty acids (MCFAs/SCFAs) as well as their metabolites. Fatty acids are closely associated with bone metabolism and associated bone disorders. In this review, we summarized the important roles and potential therapeutic implications of fatty acids in multiple bone disorders, reviewed the diverse range of critical effects displayed by fatty acids on bone metabolism, and elucidated their modulatory roles and mechanisms on specific bone cell types. The evidence supporting close implications of fatty acids in bone metabolism and disorders suggests fatty acids as potential therapeutic and nutritional agents for the treatment and prevention of metabolic bone diseases.

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“…The impact of the intestinal microbiota on the BM is becoming increasingly evident. Small microbially derived metabolites called short‐chain fatty acids modify osteoclast differentiation by shifting their metabolism from OXPHOS to glycolysis . These metabolic impacts from systemic environmental changes may modify different niche constituents and translate into aberrant immune differentiation and function.…”

Section: Fatty Acids In the Bone Marrow To Support Long‐lived Immune mentioning

confidence: 99%

Local exchange of metabolites shapes immunity

2018

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SummaryImmune cell differentiation and function depend on metabolic changes for the provision of energy and metabolites. Consequently, cellular metabolism relies on the availability of micronutrients such as vitamins and energy‐rich sources including amino acids and fatty acids. The bone marrow controls the continuous production of blood cells and is thereby reliant on the sophisticated interplay of progenitor and mature immune cells with its stromal microenvironment. The significance of stromal subsets in immunopoiesis is undisputed; however, our current knowledge is limited to their role in the production and secretion of a variety of soluble proteins such as cytokines. In contrast, the role of the haematopoietic niche in controlling and providing nutrients such as fatty acids, amino acids and vitamins, which are required for immune cell differentiation and function, remains largely elusive. In this review, we summarize the current understanding of local nutritional exchange and control between immune and stromal cells in peripheral tissue and, when it is known, in the bone marrow. The parallels found between peripheral tissues and bone marrow stroma raises the question of how local metabolism is capable of influencing haematopoiesis and immunopoiesis. A better understanding of the local exchange of nutrients in the bone marrow can be used to improve immune cell formation during ageing, after haematopoietic stem cell transplantation and during immune challenge.

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Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss

Cited by 490 publications

References 47 publications

Tuna Bone Powder Alleviates Glucocorticoid‐Induced Osteoporosis via Coregulation of the NF‐κB and Wnt/β‐Catenin Signaling Pathways and Modulation of Gut Microbiota Composition and Metabolism

Tuna Bone Powder Alleviates Glucocorticoid‐Induced Osteoporosis via Coregulation of the NF‐κB and Wnt/β‐Catenin Signaling Pathways and Modulation of Gut Microbiota Composition and Metabolism

Therapeutic potentials and modulatory mechanisms of fatty acids in bone

Local exchange of metabolites shapes immunity

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