3828d4c9bc8a3dd7885269c36a68841b cells-13-01145.pdf 013a2cf67d35dcd2f14319b5c452dd7ecd0e71a5 cells-13-01145.pdf 088ac540cd286d06949e92a48c21fd556803d2d4d5a4e62a9d2cf9ec07d4ca00 cells-13-01145.pdf Title: Microbiota and Resveratrol: How Are They Linked to Osteoporosis? Subject: Osteoporosis (OP), which is characterized by a decrease in bone density and increased susceptibility to fractures, is closely linked to the gut microbiota (GM). It is increasingly realized that the GM plays a key role in the maintenance of the functioning of multiple organs, including bone, by producing bioactive metabolites such as short-chain fatty acids (SCFA). Consequently, imbalances in the GM, referred to as dysbiosis, have been identified with a significant reduction in beneficial metabolites, such as decreased SCFA associated with increased chronic inflammatory processes, including the activation of NF-B at the epigenetic level, which is recognized as the main cause of many chronic diseases, including OP. Furthermore, regular or long-term medications such as antibiotics and many non-antibiotics such as proton pump inhibitors, chemotherapy, and NSAIDs, have been found to contribute to the development of dysbiosis, highlighting an urgent need for new treatment approaches. A promising preventive and adjuvant approach is to combat dysbiosis with natural polyphenols such as resveratrol, which have prebiotic functions and ensure an optimal microenvironment for beneficial GM. Resveratrol offers a range of benefits, including anti-inflammatory, anti-oxidant, analgesic, and prebiotic effects. In particular, the GM has been shown to convert resveratrol, into highly metabolically active molecules with even more potent beneficial properties, supporting a synergistic polyphenol–GM axis. This review addresses the question of how the GM can enhance the effects of resveratrol and how resveratrol, as an epigenetic modulator, can promote the growth and diversity of beneficial GM, thus providing important insights for the prevention and co-treatment of OP. Keywords: resveratrol; microbiome; dysbiosis; osteoporosis; gut–bone axis; prebiotics; epigenetics; bone metabolism Author: Christine Meyer, Aranka Brockmueller, Vicenç Ruiz de Porras and Mehdi Shakibaei Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Mon Jul 8 03:21:26 2024 CEST ModDate: Mon Jul 8 03:24:38 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 44 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1769945 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- DXMKTW+VnURWPalladioL Type 1 Custom yes yes yes 10 0 KESBIZ+EURM10 Type 1 Builtin yes yes yes 16 0 RUVOIS+URWPalladioL-Bold Type 1 Custom yes yes yes 21 0 FSQRXQ+URWPalladioL-Roma Type 1 Custom yes yes yes 27 0 WYNLSV+URWPalladioL-Ital Type 1 Custom yes yes yes 32 0 ZJBXVH+CMSY10 Type 1 Builtin yes yes yes 37 0 PFKOHU+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 53 0 ERPOGD+PazoMath-Italic Type 1 Builtin yes yes yes 70 0 MKMFKB+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 93 0 MKMEEB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 96 0 MKMEEC+PalatinoLinotype CID TrueType Identity-H yes yes yes 99 0 MKMEED+PalatinoLinotype TrueType WinAnsi yes yes no 105 0 MKMEEF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 108 0 MKMELF+PalatinoLinotype TrueType MacRoman yes yes no 111 0 MKMEEB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 124 0 MKMEEC+PalatinoLinotype CID TrueType Identity-H yes yes yes 127 0 MKMEED+PalatinoLinotype TrueType WinAnsi yes yes no 133 0 MKMEEF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 136 0 MKMELF+PalatinoLinotype TrueType MacRoman yes yes no 139 0 MKMFKB+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 152 0 MKMICF+PalatinoLinotype,Italic TrueType MacRoman yes yes no 155 0 MKMEEB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 158 0 MKMEEC+PalatinoLinotype CID TrueType Identity-H yes yes yes 161 0 MKMEED+PalatinoLinotype TrueType WinAnsi yes yes no 167 0 MKMEEF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 170 0 MKMELF+PalatinoLinotype TrueType MacRoman yes yes no 173 0 MKMFKB+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 205 0 MKMKKH+TimesNewRoman CID TrueType Identity-H yes yes yes 208 0 MKMEEB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 214 0 MKMEEC+PalatinoLinotype CID TrueType Identity-H yes yes yes 217 0 MKMEED+PalatinoLinotype TrueType WinAnsi yes yes no 223 0 MKMEEF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 226 0 MKMELF+PalatinoLinotype TrueType MacRoman yes yes no 229 0 FZLVCN+EURM7 Type 1 Builtin yes yes yes 239 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-07-01 02:42:47 CEST RepresentationInformation: cells-13-01145.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-06-30 16:42:28 CEST Size: 1769945 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 1362 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Osteoporosis Destination: section.2 Item: Title: Gut Microbiota and Resveratrol Destination: section.3 Children: Item: Title: Cross-Talk between Microbiota and Organs Destination: subsection.3.1 Children: Item: Title: Epigenetic Modulation Destination: subsubsection.3.1.1 Item: Title: Gut Bone Axis Destination: subsubsection.3.1.2 Item: Title: Risk Factors for Developing Dysbiosis Destination: subsection.3.2 Item: Title: Significance of Dysbiosis in Chronic Inflammatory Diseases Destination: subsection.3.3 Item: Title: Dysbiosis-Induced Osteoporosis Destination: subsection.3.4 Item: Title: Resveratrol Destination: subsection.3.5 Children: Item: Title: Resveratrol-Microbiota-Axis Destination: subsubsection.3.5.1 Item: Title: Resveratrol as a Prebiotic Active Agent Destination: subsubsection.3.5.2 Item: Title: Gut Microbiota Derived Resveratrol Metabolites Destination: subsubsection.3.5.3 Item: Title: Resveratrol as a Phytoestrogen for Osteoporosis Destination: subsubsection.3.5.4 Item: Title: Resveratrol as Epigenetic Modulator for Osteoporosis Destination: subsubsection.3.5.5 Item: Title: Clinical Evidence Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: Microbiota and Resveratrol: How Are They Linked to Osteoporosis? Author: Christine Meyer, Aranka Brockmueller, Vicenç Ruiz de Porras and Mehdi Shakibaei Subject: Osteoporosis (OP), which is characterized by a decrease in bone density and increased susceptibility to fractures, is closely linked to the gut microbiota (GM). It is increasingly realized that the GM plays a key role in the maintenance of the functioning of multiple organs, including bone, by producing bioactive metabolites such as short-chain fatty acids (SCFA). Consequently, imbalances in the GM, referred to as dysbiosis, have been identified with a significant reduction in beneficial metabolites, such as decreased SCFA associated with increased chronic inflammatory processes, including the activation of NF-B at the epigenetic level, which is recognized as the main cause of many chronic diseases, including OP. Furthermore, regular or long-term medications such as antibiotics and many non-antibiotics such as proton pump inhibitors, chemotherapy, and NSAIDs, have been found to contribute to the development of dysbiosis, highlighting an urgent need for new treatment approaches. A promising preventive and adjuvant approach is to combat dysbiosis with natural polyphenols such as resveratrol, which have prebiotic functions and ensure an optimal microenvironment for beneficial GM. Resveratrol offers a range of benefits, including anti-inflammatory, anti-oxidant, analgesic, and prebiotic effects. In particular, the GM has been shown to convert resveratrol, into highly metabolically active molecules with even more potent beneficial properties, supporting a synergistic polyphenol GM axis. This review addresses the question of how the GM can enhance the effects of resveratrol and how resveratrol, as an epigenetic modulator, can promote the growth and diversity of beneficial GM, thus providing important insights for the prevention and co-treatment of OP. 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