Article Introduction:
Osteoporosis is characterized by low bone mass and trabecular bone degeneration, and is a common bone disease among the elderly, especially in postmenopausal women. The imbalance of bone metabolism and increased levels of inflammatory factors caused by estrogen deficiency or aging are closely related to the decrease in bone mass. Engaging in sports activities is crucial for maintaining bone mass and preventing bone diseases. In a randomized controlled trial, postmenopausal women with decreased bone mass showed significant improvement in bone strength through high-intensity resistance and impact exercise. Similarly, in a mouse model of osteoporosis induced by ovariectomy (OVX), exercise is not only a powerful means of combating bone loss, but also promotes angiogenesis by increasing extracellular vesicle miRNA levels in the blood. However, the detailed mechanism of the protective effect of exercise on the skeletal system is still largely unclear. A deep understanding of these mechanisms is crucial for developing innovative methods for preventing and treating osteoporosis.
Dr. Run Run Shaw Hospital affiliated with Zhejiang University School of Medicine, Zhejiang Key Laboratory of Musculoskeletal System Degeneration and Regeneration Transformation, Zhejiang Hospital of Traditional Chinese and Western Medicine, Jiangnan Hospital affiliated with Zhejiang University of Chinese Medicine, and the First Affiliated Hospital of Zhejiang University School of Medicine jointly published an article titled "Exercise ameliorates osteopenia in mice via intestinal microbiota mediated bile acid metabolism pathway" in Theranos, Volume 15, Issue 5, 2025. Research has found that exercise improves bone loss in mice, and gut microbiota plays an important role in it. Fecal microbiota transplantation matched with exercise can activate the Apelin signaling pathway and regulate bile acid metabolism, providing new ideas for the treatment of osteoporosis.
Research background:
Osteoporosis is common in elderly and postmenopausal women, and exercise is beneficial for bone health, but the mechanism of exercise's protective effect on bones is unclear. The gut microbiota is related to bone homeostasis, and its role in exercise mediated bone benefits remains to be explored.
Research methods:
Select female 8-week-old OVX mice and 18 month old male aged mice for treadmill exercise training. Using techniques such as antibiotic treatment, fecal microbiota transplantation (FMT), 16S rRNA sequencing, metabolomics analysis, transcriptome sequencing, etc., to explore the role and mechanism of gut microbiota in improving bone loss through exercise.
Research results:
1. The impact of gut microbiota on the protective effect of exercise on bone: Antibiotic treatment inhibits the protective effect of exercise on bone loss in OVX mice; Exercise matched FMT can improve the bone structure of OVX mice, enhance osteoblast activity, inhibit osteoclast formation, and promote osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs).
2. Exercise matched FMT activates the apelin signaling pathway: FMT activates the apelin signaling pathway, promoting osteogenesis and inhibiting adipogenesis. When this pathway is blocked, the bone promoting effect of exercise matched FMT is inhibited.
3. Exercise and FMT improve intestinal barrier and inhibit inflammation: Exercise and exercise matched FMT increase the number of goblet cells, reduce intestinal permeability, inhibit the expression of inflammatory factors, and reduce systemic inflammation.
4. Exercise training changes gut microbiota: Exercise increases the richness of gut microbiota, and exercise matched FMT transforms the gut microbiota of recipient mice to that of donor mice. Supplementing with Helicobacter pylori can improve bone quality in OVX mice.
5. Bile acid metabolism pathway mediates bone benefits of exercise matched FMT: Exercise matched FMT alters gut metabolite profiles, with significant increases in taurine (Tau) and ursodeoxycholic acid (UDCA). Supplementing Tau and UDCA can improve bone mass in OVX and aged mice and activate the apelin signaling pathway.
The article involves treadmill exercise:
Treadmill training is conducted as previously described. Use KW-PT eight channel animal treadmill (Nanjing Calvin Biotechnology Co., Ltd.) for exercise training. When mice start training, they exercise for 60 minutes a day at a speed of 6 meters per minute, increasing their speed by 1 meter per minute each day until they reach a stable 12 meters per minute and continue for 60 minutes. Throughout the entire 8-week exercise plan, train according to this routine every day.
Research conclusion:
Exercise alleviates osteoporosis in mice through the bile acid metabolism pathway mediated by the gut microbiota. Exercise and exercise matched FMT can improve intestinal health, activate the Apelin signaling pathway, and regulate bone fat balance. Tau and UDCA are expected to become potential drugs for the prevention and treatment of osteoporosis.