Gut microbiota- bone axis

The gut microbiota (GM) is an important regulator of body homeostasis, including intestinal and extraintestinal effects. This review focuses on the GM-bone axis, which we define as the effect of the gutassociated microbial community or the molecules they synthesize, on bone health. While research in this field is limited, findings from preclinical studies support that gut microbes positively impact bone mineral density and strength parameters. Moreover, administration of beneficial bacteria (probiotics) in preclinical models has demonstrated higher bone mineralization and greater bone strength. The preferential bacterial genus that has shown these beneficial effects in bone is Lactobacillus and thus lactobacilli are among the best candidates for future clinical intervention trials. However, their effectiveness is dependent on stage of development, as early life constitutes an important time for impacting bone health, perhaps via modulation of the GM. In addition, sex-specific difference also impacts the efficacy of the probiotics. Although auspicious, many questions regarding the GM-bone axis require consideration of potential mechanisms; sex-specific efficacy; effective dose of probiotics; and timing and duration of treatment. Abbreviations: BMC: bone mineral content; BMD: bone mineral density; BV/TV%: bone volume as a percentage of total volume; CONV-D: conventionalized; CONV-R: conventionally-raised; CD: Crohn's disease; DXA: Dual-energy X-ray Absorptiometry; GF: germ-free; GIT: gastrointestinal tract; GM: gut microbiota; 5-HT: 5-hydroxytryptamine; IBD: inflammatory bowel disease; IL: interleukin; IBS: irritable bowel syndrome; LPS: lipopolysaccharide; LBP: LPS binding protein; OCL: osteoclast; OPG: osteoprotegrin; Ovx: ovariectomized; RANK: receptor activator of nuclear factor kappa-B; RANKL: receptor activator of nuclear factor kappa-B ligand; SAM: senescence accelerated mice; SERT: serotonin transporter; TLRs: toll-like receptors; Tph1: tryptophan hydroxylase-1; TNF: tumor necrosis factor; UC: ulcerative colitis