Roles of gut metabolites on bone mineralization and remodeling: impact of metabolic dysregulation on the gut-immune-bone axis.

Gut microbiota, the community of microorganisms in the gastrointestinal (GI) tract, plays many critical roles in the maintenance of an individual's health by regulating bone metabolism. Bone mass has been linked to the GI system because nutrients (minerals) are absorbed to maintain bone homeostasis. Dysbiosis of gut microbiota due to metabolic deregulation associated with obesity, fatty liver, and inflammatory status of an individual promotes altered gut microbial diversity, gut-epithelial integrity, releases of harmful gut metabolites those could mediate malabsorption of nutrients such as calcium, vitamin D, omega-3 fatty acids, phosphorous, magnesium, and other key minerals essential for bone mineralization and remodeling in maintaining bone mass through the controlled processes of bone formation and resorption activities. Postbiotics and related products show promising roles in restoring intestinal barrier integrity by reducing systemic inflammation and stimulating the immune system, thereby preventing bone loss. Manipulating the host gut microbiota by sustained release of microbiota-derived metabolites at target sites can help modulate gut homeostasis by regulating redox balance, macrophage polarization, and controlling systemic inflammation. Although several reviews highlighted the roles of gut microbiota, the specific roles of gut metabolites in bone metabolism and associated disorders as a result of metabolic dysregulation remain limited. This narrative review highlights the emerging roles of gut metabolites, postbiotics and related products in regulating intestinal integrity, immune responses, and inflammation, thereby protecting against bone loss.