Alginate oligosaccharides relieve estrogen-deprived osteosarcopenia by affecting intestinal Th17 differentiation and systemic inflammation through the manipulation of bile acid metabolism

Abstract

Alginate oligosaccharides (AOS) have gained attention for their capacity to regulate human health as prebiotics. Osteosarcopenia is a progressive disease of the musculoskeletal system and result in heavy burden of patients. Studies suggest that gut microbiota is involved in the pathogenesis of osteosarcopenia, whether AOS can improve the symptoms of osteosarcopenia by modulating gut microbiota remains to be elucidated. In this study, we proved that 200 mg/kg body weight AOS (MW = 4.9 kDa, G/M = 1.88) treatment significantly increased bone mass, boosted muscle function, and promoted gut barrier integrity in ovariectomized (OVX) mice. After AOS treatment, a marked reduction in the proportion of intestinal Th17 subsets and in peripheral levels of relevant inflammatory cytokines was observed compared to the OVX group. 16S rRNA sequencing indicated that AOS treatment could restore the imbalance of gut microbiota caused by estrogen deficiency. Additionally, the impact of AOS on bile acid changes was revealed according to metabolomics. In particular, the Th17 differentiation inhibitor, such as isoLCA, were significantly upregulated after AOS treatment. In conclusion, AOS can alleviate the symptoms of osteoporosis by modulating the relative abundance of gut microbiota and bile acid metabolism, thereby reducing the proportion of intestinal Th17 cells and peripheral Inflammation.

Keywords: Alginate oligosaccharides; Bile acids; Gut microbiota; Osteosarcopenia; Prebiotics; Th17.