Phytosterols Protect against Osteoporosis by Regulating Gut Microbiota

Abstract

Osteoporosis is increasingly prevalent worldwide, representing a major health burden. However, there is a lack of nutritional strategies for osteoporotic therapy. Phytosterols, as natural bioactive compounds, have the potential to alleviate osteoporosis. In this study, a glucocorticoid-induced osteoporosis mouse model and treatment with low and high concentrations of phytosterols for 4 weeks were established. The results demonstrated that compared to the control group, low-concentration phytosterols (LP) (0.3 mg/mL) increased bone mass, improved trabecular microstructure, reduced serum levels of cross-linked C-telopeptide of type I collagen (CTX-1), and elevated serum levels of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). Conversely, high-concentration phytosterols (0.5 mg/mL) showed no effect. Additionally, we validated the effect of LP in ameliorating osteoporosis using an ovariectomized (OVX)-induced osteoporosis mouse model. Mechanistically, phytosterols altered the microbial composition to counteract glucocorticoid-induced gut microbiota disorder and improve the length and morphology of the small intestine. Particularly, based on selection strategy and correlation analysis, phytosterols increased the relative abundance of Ruminococcus and decreased the relative abundance of Bilophila, which were significantly associated with glucocorticoid-induced osteoporosis indications. Overall, these findings suggest that phytosterols regulate gut microbiota to increase bone mass, thereby exerting an antiosteoporotic effect.

Associations of healthy eating index-2015 with osteoporosis and low bone mass density in postmenopausal women: a population-based study from NHANES 2007–2018

“…Meanwhile, beans are a good source of plant protein and proteins intake is positively associated with BMD and negatively related with osteoporosis regardless of protein source ( 51 – 53 ). Our results additionally demonstrated the beneficial effect of higher refined-grains score and lower refined-grains intake, and this may be attributed to the fact that refined grains are known to contain fewer vitamins, minerals, and phytosterols that are important for bone health and protection against osteoporosis ( 54 ). Furthermore, refined grains were found to decrease BMD by modulating osteoprotegerin and receptor activator of nuclear factor kappa B (NF-κB) in male rats ( 55 ).…”

Characteristics of the gut microbiota and serum metabolites in postmenopausal women with reduced bone mineral density

“…Furthermore, the depletion of the butyrate-producing Firmicutes bacterium Fusicatenibacter in OS patients could produce a beneficial effect on maintaining the stability of the intestinal lumen environment ( Tian et al., 2023 ). Ruminococcus was regarded as a beneficial bacterium related to the prevention of osteoporosis in studies focusing on the anti-osteoporosis mechanism of active ingredients ( Han et al., 2023 ; Xiao et al., 2023 ). To the best of our knowledge, Agathobacter has not been reported to be associated with osteoporosis.…”

Genetically Predicted Elevated Circulating 3,4-Dihydroxybutyrate Levels Mediate the Association between families.Christensenellaceae and Osteoporosis Risk: A Mendelian randomization study

“…Existing research suggests a crucial role for gut microbiota in the development of osteoporosis. Xiao, XY et al [4] in a mouse experiment, found that phytosterols regulate gut microbiota to increase bone mass, exerting an antiosteoporotic effect. Wang, JH et al [5] conducted a diversity analysis of gut microbiota in osteoporosis and osteopenia patients, identifying statistically signi cant differences compared to a normal population, indicating that gut microbiota may be a critical factor in osteoporosis development.…”