Intermittent fasting triggers interorgan communication to improve the progression of diabetic osteoporosis

Diabetic osteoporosis is a disease that seriously affects health, and intermittent fasting is a promising dietary approach to manage diabetes. The objective of our study was to analyze the effects of intermittent fasting on diabetic osteoporosis and its possible mechanisms. Streptozotocin-induced diabetes in mice was treated by intermittent fasting. Micro-CT and Immunostaining techniques were utilized to evaluate glycogen synthesis and morphological changes in the tibia. Gut microbiota analysis involved 16S rRNA gene amplification and sequencing. Liquid chromatography-mass spectrometry was employed, and quantitative real-time PCR assessed gene expression levels. Our study found that intermittent fasting improved blood glucose levels in diabetic mice and simultaneously enhanced cancellous bone microstructure, including BMD, BV/TV, Tb.Th, and Tb.Sp, which was revised by intervention with intermittent fasting. Intermittent fasting increased Christensenellaceae Chr) flora abundance. To further validate the role of Chr in diabetic osteoporosis treated with intermittent fasting, we used a gut microbiota transplanting and elimination experiment and Chr supplementation experiment, and the result found that Chr supplementation improved bone mass and microstructure in diabetic osteoporosis mice. In addition, Christensenellaceae facilitated the release of exosomes, which promote osteoclast activity, and exosome sequencing analysis showed miR551b upregulation in Christensenellaceae-derived exosomes, and the miR551b improves bone parameters in diabetic osteoporosis mice by supplement or inhibiting miR551b experiments. In conclusion, our study highlights the role of intermittent fasting in improving osteoporosis in diabetes by regulating changes in the abundance of Chr in the gut microbiota and improving the exosomes miR551b secreted by Chr, which in turn improves osteoblast activity. These findings provide a mechanism of intermittent fasting in managing osteoporosis via the gut microbiota-bone axis, potentially leading to innovative therapeutic approaches for diabetes-mediated osteoporosis.