Fucoidan, as a marine bioactive substance, has shown great potential in regulating the bone-gut axis

Fucoidans exhibit numerous biological activities, including anti-inflammatory and hypolipidemic effects. Although its potential in regulating intestinal flora has been demonstrated, studies on its impact on bone metabolism and its relationship with the bone-gut axis remain limited. Therefore, this study was undertaken to explore the effects of fucoidan on the gut-bone axis in ovariectomized mice with osteoporosis. Twenty-one SPF ICR female mice were used in this study, distributed as follows: sham-operated (7), ovariectomized (7), and ovariectomized + fucoidan (200 mg/kg, 7). Subsequently, body indices, blood chemistry, bone specimens, short-chain fatty acids, fecal microbiota content, transmission electron microscopy, and RNA-seq transcriptome analysis were assessed, and statistical analysis was performed. The efficacy of fucoidan in treating osteoporosis was demonstrated in this study. Fucoidan treatment led to a significant increase in bone mineral density and procollagen N-terminal propeptide levels and a significant decrease in body weight and C-terminal peptide of human type I collagen and triglyceride levels (P < 0.05). Fucoidan promoted the health of ovariectomized mice, possibly by regulating the gut-bone axis. It significantly decreased the abundance of Ruminococcaceae UG-014, Parasutterella, and Muribaculum and increased the abundance of Akkermansia and Dubosiella (P < 0.05). Moreover, fucoidan protected the intestinal barrier and increased the acetic acid ratio. These changes in microbiota were significantly correlated with clinical features of osteoporosis (P < 0.05). Lipid metabolism emerged as a pivotal factor in the association between the intestinal microbiota and osteoporosis. Notably, intestinal transcriptome sequencing revealed significant changes in the expression of genes related to lipid metabolism (Adipoq, Angptl4, Adrb3, and C3ar1) and bone metabolism (Clec3b, Nrtn, Bpnt2, Ccn3, and Lama2) (P < 0.05). Overall, this study provides valuable insights into the unexplored microbiome-based mechanism by which fucoidan improves bone quality in ovariectomized mice, possibly by regulating the gut-bone axis.