Microbiota and Resveratrol: How Are They Linked to Osteoporosis?

Abstract

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-κB 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: bone metabolism; dysbiosis; epigenetics; gut–bone axis; microbiome; osteoporosis; prebiotics; resveratrol.

Figure 1

Several causes for the depletion of beneficial gut bacteria. Abbreviations: NSAIDs—Nonsteroidal anti-inflammatory drugs, Vit—Vitamin.

Figure 2

Functional axis between the intestinal microbiota, its metabolic products, and numerous body organs and chronic diseases.

Figure 3

Microbial signatures associated with osteoporosis. Created with BioRender.org https://app.biorender.com/ (accessed on 1 May 2024).

Figure 4

The resveratrol–microbiota axis modulates bone remodeling in primary and secondary osteoporosis. The up arrow (↑) indicates up-regulation and the down arrow (↓) indicates suppression. Abbreviations: A. equolifaciens—Adlercreutzia equolifaciens; ALP—alkaline phosphatase; B. infantis—Bifidobacterium infantis; BMP—bone morphogenetic protein; Col I—Collagen I; NF-κB—nuclear factor-kappa B; RANKL—receptor activator of NF-κB ligand; ROS—reactive oxygen species; Runx2—Runt-related transcription factor 2; SCFA—short chain fatty acids; S. equolifaciens—Slackia equolifaciens; Sirt1—Sirtuin 1; TMAO—Trimethylamine N-oxide.