Gut microbiota and bone metabolism

Abstract

Osteoporosis is the most common metabolic skeletal disease. It is characterized by the deterioration of the skeletal microarchitecture and bone loss, leading to ostealgia, and even bone fractures. Accumulating evidence has indicated that there is an inextricable relationship between the gut microbiota (GM) and bone homeostasis involving host–microbiota crosstalk. Any perturbation of the GM can play an initiating and reinforcing role in disrupting the bone remodeling balance during the development of osteoporosis. Although the GM is known to influence bone metabolism, the mechanisms associated with these effects remain unclear. Herein, we review the current knowledge of how the GM affects bone metabolism in health and disease, summarize the correlation between pathogen‐associated molecular patterns of GM structural components and bone metabolism, and discuss the potential mechanisms underlying how GM metabolites regulate bone turnover. Deciphering the complicated relationship between the GM and bone health will provide new insights into the prevention and treatment of osteoporosis.

Gut Microbiota and Serum Metabolic Signatures of High-Fat-Induced Bone Loss in Mice

“…Parasutterella was initially defined as a core component of the human and mouse GM that can contribute to host health in 2019 ( Ju et al., 2019 ). The key role of Parasutterella is to enhance the catabolism of tryptophan, tyrosine, and bile acid components ( Ju et al., 2019 ), which are potentially related to bone metabolism ( Lu et al., 2021 ). A recent study has identified a strain of Odoribacter that protects against colitis and colorectal cancer, and demonstrated a crucial role in inducing immunosuppressive Th17 cells ( Xing et al., 2021 ).…”

“…Metabolites bridge the distance between the GM and skeletal system ( Zaiss et al., 2019 ). Various GM-derived metabolites have displayed bone metabolism-related bioactivities ( Lu et al., 2021 ). Purine metabolism is one of the metabolic pathways enriched by differential metabolites after HFD ( Figure 4G ).…”

“…The alteration of GM induced by HFD not only enhanced carbohydrate and lipid metabolism, but also evoked the metabolism of several amino acids ( Figure 3G ). Circulating amino acids and the metabolites play important roles in bone metabolism ( Lu et al., 2021 ), such as tryptophan, hydroxyproline, cysteine, proline, and glutamine ( You et al., 2014 ; Qi et al., 2016 ; Miyamoto et al., 2017 ; Zhao et al., 2018 ; Su et al., 2019 ). For instance, typtophan metabolites (indoles, indole derivatives, and kynurenine) have dual regulatory effects on both osteoclastogenesis and osteoblastogenesis via aryl hydrocarbon receptor-mediated NFATc1, ERK, and p38 MAPK pathways ( Eisa et al., 2020 ; Liu et al., 2020a ; Liu et al., 2020b ).…”

“…Gut microbiota (GM) is a primary biological barrier for nutrient entry into the human body, abnormal perturbation of which leads to skeletal deterioration ( Lu et al., 2021 ). The composition and function of GM can be altered rapidly by dietary nutrition ( David et al., 2014 ; Aguirre et al., 2016 ); in turn, the absorption, utilization, and metabolism of dietary nutrition will be affected by the altered GM ( Gentile and Weir, 2018 ).…”

The Role of Depletion of Gut Microbiota in Osteoporosis and Osteoarthritis: A Narrative Review

“…Currently, there are many studies on the relationship between intestinal flora and bone metabolism ( 6 ). The interactions of the host microbiota are key factors for health and can ultimately be used to develop a stable microbial community ( 7 ).…”