Astragalus polysaccharide and Clostridium butyricum synergistically inhibit bone loss in mice with humanized intestinal flora

Abstract: Bone loss is one of the major challenges in spaceflight, limiting the ability of humans to explore space. In recent years, studies of the gut-bone axis have revealed the profound effects of the gut microbiota on bone health through the regulation of metabolites (e.g., short-chain fatty acids, SCFAs) and the immune system. Short-chain fatty acids (e.g., butyric acid) not only protect the intestinal mucosal barrier, but also regulate bone metabolism through the gut-bone axis and improve osteoporosis. In addition, astragalus polysaccharide (APS) has been shown to regulate the composition of intestinal flora, promote the production of SCFAs, and improve intestinal health through immunomodulation.In this study, we explored the effects of Astragali polysaccharide and Clostridium butyricum mixed feeding (APS-CB) on bone loss in mice under simulated weightlessness conditions based on the concept of synergistic effect. We used a humanized intestinal flora mouse model and showed that APS-CB significantly inhibited bone loss caused by simulated weightlessness. Specific mechanisms included that APS-CB increased the amount of short-chain fatty acids, especially butyric acid, in mouse feces, while increasing the abundance of Bacillariophyta (Akkermansia) in the intestine and decreasing the serum level of the bone resorption marker CTX-1. These results suggest that by modulating the gut-bone axis, APS-CB is effective in improving bone metabolism.This finding not only provides a new intervention strategy for astronauts' bone health in space, but also provides a theoretical basis for improving bone metabolism by regulating the gut microbiota. Future studies will further explore the underlying mechanisms and provide scientific support for the development of a gut-bone axis-based osteoporosis treatment program.