The relationship between gut microbiota and bone remodeling.

Overview of Osteoporosis

Osteoporosis (Osteoporpsis, OP) is a systemic bone disease caused by multiple factors. Ancient Chinese medical texts also record terms like 'bone decay', 'bone atrophy', and 'bone pain'. Osteoporosis is mainly characterized by a decrease in bone mass, destruction of bone microstructure, and a decline in bone strength, leading to increased bone fragility and a higher risk of fractures. However, before a fracture occurs, patients do not exhibit apparent symptoms, which is why osteoporosis is also referred to as a silent disease without obvious symptoms. This condition can occur at any age and in different genders, with higher incidence rates in elderly men and postmenopausal women.

The renewal of human bones, known as bone remodeling, occurs throughout life and includes two processes: bone resorption and bone formation. The process of bone remodeling involves the continuous degradation and absorption of old bone tissue by osteoclasts, which are derived from mononuclear macrophages originating from hematopoietic stem cells, while new bone matrix is constructed by osteoblasts differentiated from bone marrow mesenchymal stem cells. When the dynamic balance of bone remodeling is disrupted, the functions of osteoclasts and osteoblasts become imbalanced, leading to a situation where the rate of bone resorption exceeds that of bone formation, resulting in bone loss and the onset of osteoporosis.

Overview of Gut Microbiota

The gastrointestinal tract is home to a vast and diverse community of microorganisms known as gut microbiota (GM), with numbers exceeding 10^14 and a genomic gene count approximately 150 times that of the human host genome. The gut microbiota functions like an organ in the human body, and in response to external environmental stimuli and other factors, it alters the types and quantities of gut microbiota, affecting the functions of the enteric nervous system, the intestinal endocrine system, the immune system, and intestinal permeability. It plays a crucial role in food digestion, vitamin nutrition, defense against invading pathogens, and immune stimulation.

The Relationship Between Gut Microbiota and Bone Remodeling

• Gut Microbiota, Sex Hormones, and Bone Remodeling

The role of sex hormones in bone growth and development is widely recognized. Estrogen receptors and androgen receptors are expressed on the surface of osteoblasts, and estrogen receptors are also present on the surface of osteoclasts and other cells related to bone remodeling. Estrogen and androgens have the ability to inhibit osteoblast apoptosis and stimulate osteoblast proliferation and maturation. Estrogen can also directly induce osteoclast apoptosis and inhibit the production of tumor necrosis factor (TNF) and interleukin-1 (IL-1), thereby indirectly suppressing bone resorption. Numerous studies have shown that various gut microorganisms can influence the metabolism of sex hormones, and there exists an interaction between sex hormones and gut microbiota: Clostridium can synthesize at least two types of enzymes that affect steroid hormone metabolism; estrogen and progesterone can directly influence the metabolic pathways of Lactobacillus, thereby regulating the overall ecological structure of the gut microbiota.

• Gut Microbiota, Serotonin, and Bone Remodeling

Serotonin is synthesized by two different tryptophan hydroxylases, Tph1 and Tph2, which regulate the synthesis of neurogenic and non-neurogenic 5-hydroxytryptamine (5-HT). 5-HT has a bidirectional regulatory effect on bone remodeling; peripheral tissue-derived 5-HT can inhibit bone formation, while centrally produced 5-HT positively influences bone mass by increasing bone formation and inhibiting bone resorption. Studies have shown that Bacillus, Streptococcus, and Escherichia coli can produce 5-HT in vitro. Additionally, in experiments with germ-free mice, the concentration of 5-HT in the serum of germ-free mice was significantly lower than that of normal mice, but the packaging and release processes of 5-HT within cells did not show significant changes. In germ-free mice at every age stage, transplantation of gut microbiota can restore the levels of 5-HT in the serum and colon.

• Gut Microbiota, Adrenal Corticosteroids, and Bone Remodeling

The connection between bone growth and calcium ions is well known, and excessive adrenal corticosteroids can inhibit the absorption of calcium ions in the intestine, leading to increased urinary calcium excretion and negative calcium balance, which affects bone mineralization. Most current research supports the view that adrenal corticosteroids negatively regulate active vitamin D. Furthermore, adrenal corticosteroids can reduce the number of vitamin D receptors, which has been confirmed in animal experiments and clinical trials. Gut microbiota can influence the synthesis and breakdown of adrenal glucocorticoids, indirectly affecting calcium ion absorption and the bone remodeling process.

• Gut Microbiota, Immune System, and Bone Remodeling

Gut microorganisms can also mediate the regulation of bone metabolism by altering the immune status of bones. Inflammatory factors such as IL-1, IL-6, TNF-α, RANKL, OPG, and CCL2 are influenced by gut microbiota. TNF-α is a key factor involved in bone resorption and can promote the formation of osteoclasts. Elevated levels of IL-1 and TNF-α can increase the risk of osteoporosis in postmenopausal women. By inhibiting the expression of IL-1 and TNF-α, the expression levels of osteogenic markers can be increased, helping to delay the onset of osteoporosis. After transplanting gut microbiota into germ-free mice, the number of bone marrow CD4+ T cells that promote osteoclast generation, osteoclasts, and osteoclast precursor cells in the mice significantly decreased, and TNF-α expression was downregulated.

Note: This article is for informational purposes only and should not be considered medical guidance.