The impact of ambient temperature on key metabolic processes, including energy expenditure and insulin sensitivity, makes it a crucial factor in the development of metabolic diseases. Osteoporosis, characterized by reduced bone mass and increased fracture risk, presents significant health concerns, particularly among post-menopausal women who also experience metabolic impairments. The limitations and side effects of current osteoporosis therapies necessitate the exploration of improved treatment options. The gut microbiota serves a critical function in regulating energy metabolism and influencing susceptibility to diseases.

In this thesis, we report that warm exposure induced adipose tissue whitening, reduced caloric uptake, and intestinal adaptive surface length. Notably, warmth led to improvement in oral glucose tolerance concomitant with modulating bone metabolism. Furthermore, warm exposure was preventive against ovariectomy-induced bone loss by increasing trabecular bone mass and biomechanical bone strength. These effects were partially mediated by changes in gut microbiota composition. Combinatorial metagenomics/metabolomics analysis revealed enhanced bacterial polyamine biosynthesis in warm conditions. The administration of polyamines demonstrated enhanced bone strength, whereas inhibiting polyamine biosynthesis in vivo reversed the beneficial effect on bone.

Next, we identified bacterial species from the warm-adapted gut microbiota to investigate their effect on bone and metabolic health in the mice model of post-menopausal osteoporosis. Supplementation of these identified bacteria to ovariectomized mice, increased bone density, strength, and glucose tolerance. Additionally, the administration of the candidate bacteria with alendronate, a bisphosphonate currently used for osteoporosis treatment, exhibited a synergistic effect in mice where osteoporosis progression continued for two months post-ovariectomy, leading to improvements in body weight, glucose tolerance, insulin sensitivity, and bone strength. Our findings highlight the therapeutic potential of warm-adapted gut microbiota for post-menopausal osteoporosis. We identified bacterial species that hold great importance as therapeutic agents for improving bone health and metabolic outcomes in this disease.