Effects of the gut microbiota on bone mass

•Studies in germ-free (GF) mice demonstrate that the gut microbiota (GM) is a regulator of bone mass. •The GM affects bone mass via effects on the immune status, which in turn regulates osteoclastogenesis. •Probiotic and prebiotic treatments may impact GM composition and affect bone metabolism. •The GM may be a novel therapeutic target for osteoporosis. The gut microbiota (GM), the commensal bacteria living in our intestine, performs numerous useful functions, including modulating host metabolism and immune status. Recent studies demonstrate that the GM is also a regulator of bone mass and it is proposed that the effect of the GM on bone mass is mediated via effects on the immune system, which in turn regulates osteoclastogenesis. Under normal conditions, the skeleton is constantly remodeled by bone-forming osteoblasts (OBs) and bone-resorbing osteoclasts (OCLs), and imbalances in this process may lead to osteoporosis. Here we review current knowledge on the possible role for the GM in the regulation of bone metabolism and propose that the GM might be a novel therapeutic target for osteoporosis and fracture prevention. The gut microbiota (GM), the commensal bacteria living in our intestine, performs numerous useful functions, including modulating host metabolism and immune status. Recent studies demonstrate that the GM is also a regulator of bone mass and it is proposed that the effect of the GM on bone mass is mediated via effects on the immune system, which in turn regulates osteoclastogenesis. Under normal conditions, the skeleton is constantly remodeled by bone-forming osteoblasts (OBs) and bone-resorbing osteoclasts (OCLs), and imbalances in this process may lead to osteoporosis. Here we review current knowledge on the possible role for the GM in the regulation of bone metabolism and propose that the GM might be a novel therapeutic target for osteoporosis and fracture prevention. is highly correlated with bone strength and is commonly measured and used in the clinic to predict fracture risk. According to the World Health Organization's guidelines, osteoporosis is diagnosed when the BMD is more than or equal to 2.5 standard deviations below that of a young adult reference population. refers to an imbalance between putative species of ‘protective’ versus ‘harmful’ intestinal bacteria. is an animal that is free of bacteria or contaminants or into which a known microorganism or contaminant has been introduced for research purposes. are plant-derived polysaccharides. The inulins belong to a class of dietary fibers known as fructans. refers to the microflora and microfauna in an ecosystem. are cells that make bone by producing a matrix that then becomes mineralized. The skeleton is preserved by a balance between the activity of OBs that form bone and OCLs that break it down. are cells that break down bone and are responsible for bone resorption. OCLs are large multinucleate cells that differentiate from hematopoietic stem cells in the bone marrow. are non-digestible fiber compounds that pass undigested through the upper part of the gastrointestinal tract and act as a substrate for commensal bacteria. They help promote the growth and activity of advantageous bacteria in the gut. the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO) definition of probiotics is ‘live microorganisms which when administered in adequate amounts confer a health benefit on the host’. Probiotics such as lactobacilli and bifidobacteria are beneficial to the host because they help improve the intestinal bacterial balance.