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

Guan, Zhiyuan; Luo, Liying; Liu, Shengfu; Guan, Zhiqiang; Li, Xu; Tao, Kun

doi:10.3389/fendo.2022.847401

Cited by 17 publications

(13 citation statements)

References 89 publications

(94 reference statements)

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“…Thus, comprehensive approaches, such as improvement of systemic peroxidation state, chronic inflammatory stress, and immune status, as well as regulation of bone homeostasis, should be taken into consideration for treating postmenopausal osteoporosis. Also, disrupted gut microbial homeostasis, iron metabolism, cellular aging and stress, advanced glycation end products, and microRNA contributed to the pathogenesis of osteoporosis (Che et al, 2020;Yang et al, 2020;Chandra and Rajawat, 2021;Ge et al, 2022;Guan et al, 2022). Thus, the influence of monotropein on these biological processes should be explored.…”

Section: Discussionmentioning

confidence: 99%

Monotropein: A comprehensive review of biosynthesis, physicochemical properties, pharmacokinetics, and pharmacology

Lai²,

Peng

et al. 2023

Front. Pharmacol.

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Monotropein, a principal natural compound in iridoid glycosides extracted from Morindae officinalis radix, has potent pharmacological activities. To understand and utilize monotropein, we systematically summarized the studies on monotropein, including its biosynthetic pathway, physicochemical properties, pharmacokinetics, and pharmacology. Interestingly, we found that the multiple bioactivities of monotropein, such as anti-osteoporosis, anti-inflammation, anti-oxidation, anti-nociception, and hepatic or renal protection, are closely associated with its capability of downregulating the nuclear factor-κB signaling pathway, inhibiting the mitogen-activated protein kinase signaling pathway, attenuating the activation of nuclear factor E2-related factor 2/heme oxygenase-1 signaling pathway, and regulating the mammalian target of rapamycin/autophagy signaling pathway. However, the clinically therapeutic effects and the potential problems need to be addressed. This review highlights the current research progress on monotropein, which provides a reference for further investigation of monotropein.

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Section: Discussionmentioning

confidence: 99%

Monotropein: A comprehensive review of biosynthesis, physicochemical properties, pharmacokinetics, and pharmacology

Lai²,

Peng

et al. 2023

Front. Pharmacol.

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“…In addition to their role in regulating regulatory T cells, probiotics also help maintain the integrity of intestinal epithelial cells (51) , which is critical for separating commensal bacteria from mucosal immune cells. In osteoporosis, the integrity of intestinal epithelial cells is often compromised (52) , leading to the expansion of Th17 cells that produce osteoclastogenic inflammatory cytokines (53) . These cytokines promote the formation of bone-resorbing osteoclasts, leading to bone loss.…”

Section: Discussionmentioning

confidence: 99%

Effect of probiotics on postmenopausal bone health: a preclinical meta-analysis

Bose,

Sharan

2023

Br J Nutr

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Postmenopausal osteoporosis is a major concern for women worldwide, due to increased risk of fractures and diminished bone quality. Recent research on gut microbiota have suggested that probiotics can combat various diseases, including postmenopausal bone loss. Although several pre-clinical studies have explored the potential of probiotics in improving postmenopausal bone loss, the results have been inconsistent, and the mechanism of action remains unclear. To address this, a meta-analysis was conducted to determine the effect of probiotics on animal models of postmenopausal osteoporosis. The bone parameters studied were Bone Mineral Density (BMD), Bone Volume Fractions (BV/TV), and hallmarks of bone formation and resorption. Pooled analysis showed that probiotic treatment significantly improves BMD and BV/TV of the ovariectomised animals. Probiotics, while not statistically significant, exhibited a tendency toward enhancing bone formation and reducing bone resorption. Next, we compared the effects of Lactobacillus sp. and Bifidobacterium sp. on osteoporotic bone. Both probiotics improved BMD and BV/TV compared to control, but Lactobacillus sp. had a larger effect size. In conclusion, our findings suggest that probiotics have the potential to improve bone health and prevent postmenopausal osteoporosis. However, further studies are required to investigate the effect of probiotics on postmenopausal bone health in humans.

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“…GM is closely related to a variety of diseases including trauma repair, osteoporosis, and Parkinson's disease (Hu et al, 2016 ; Liu, Chen, et al, 2021 ; Zmora et al, 2019 ). In our previous studies, we found that gut microbiota depletion caused by antibiotics can alleviate the progression of OA (Guan et al, 2020 ; Guan, Luo, et al, 2022 ). Changes in the abundance of certain specific gut microbiota such as Desulfovibrionales and Ruminiclostridium often lead to the progression of osteoarthritis (Yu et al, 2021 ).…”

Section: Introductionmentioning

confidence: 87%

The gut microbiota metabolite capsiate regulate SLC2A1 expression by targeting HIF‐1α to inhibit knee osteoarthritis‐induced ferroptosis

et al. 2023

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Ferroptosis is an iron‐dependent cell death that has been found to aggravate the progression of osteoarthritis (OA) and gut microbiota‐ OA axis refers to the bidirectional information network between the gut microbiota and OA, which may provide a new way to protect the OA. However, the role of gut microbiota‐derived metabolites in ferroptosis‐relative osteoarthritis remains unclear. The objective of this study was to analyze the protective effect of gut microbiota and its metabolite capsiate (CAT) on ferroptosis‐relative osteoarthritis in vivo and in vitro experiments. From June 2021 to February 2022, 78 patients were evaluated retrospectively and divided into two groups: The health group (n = 39) and the OA group (n = 40). Iron and oxidative stress indicators were determined in peripheral blood samples. And then in vivo and in vitro experiments, a surgically destabilized medial meniscus (DMM) mice model was established and treated with CAT or Ferric Inhibitor‐1 (Fer‐1). Solute Carrier Family 2 Member 1 (SLC2A1) short hairpin RNA (shRNA) was utilized to inhibit SLC2A1 expression. Serum iron was increased significantly but total iron binding capacity was decreased significantly in OA patients than healthy people (p < 0.0001). The least absolute shrinkage and selection operator clinical prediction model suggested that serum iron, total iron binding capacity, transferrin, and superoxide dismutase were all independent predictors of OA (p < 0.001). Bioinformatics results suggested that SLC2A1, Metastasis‐Associated Lung Adenocarcinoma Transcript 1 (MALAT1), and HIF‐1α (Hypoxia Inducible Factor 1 Alpha)‐related oxidative stress signaling pathways play an important role in iron homeostasis and OA. In addition, gut microbiota 16s RNA sequencing and untargeted metabolomics were used to find that gut microbiota metabolites CAT in mice with osteoarthritis were negatively correlated with Osteoarthritis Research Society International (OARSI) scores for chondrogenic degeneration (p = 0.0017). Moreover, CAT reduced ferroptosis‐dependent osteoarthritis in vivo and in vitro. However, the protective effect of CAT against ferroptosis‐dependent osteoarthritis could be eliminated by silencing SLC2A1. SLC2A1 was upregulated but reduced the SLC2A1 and HIF‐1α levels in the DMM group. HIF‐1α, MALAT1, and apoptosis levels were increased after SLC2A1 knockout in chondrocyte cells (p = 0.0017). Finally, downregulation of SLC2A1 expression by Adeno‐associated Virus (AAV) ‐SLC2A1 shRNA improves osteoarthritis in vivo. Our findings indicated that CAT inhibited HIF‐1a expression and reduced ferroptosis‐relative osteoarthritis progression by activating SLC2A1.

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

Cited by 17 publications

References 89 publications

Monotropein: A comprehensive review of biosynthesis, physicochemical properties, pharmacokinetics, and pharmacology

Monotropein: A comprehensive review of biosynthesis, physicochemical properties, pharmacokinetics, and pharmacology

Effect of probiotics on postmenopausal bone health: a preclinical meta-analysis

The gut microbiota metabolite capsiate regulate SLC2A1 expression by targeting HIF‐1α to inhibit knee osteoarthritis‐induced ferroptosis

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