Multi-omics analysis reveals new mechanistic insights underlying the osteoanabolic effects of short chain fructooligosaccharide.

Abstract

Despite evidence that short chain fructooligosaccharide (FOS) improves bone mass and intestinal mineral absorption, the mechanism driving these effects remains uncertain. This study investigated how FOS modulates molecular and cellular pathways in bone through alterations in the gut microbiota and metabolome. Eight-week-old C57BL/6 female mice were fed a control or FOS-supplemented diet (10%) for 4 weeks. Bone histomorphometry, femur and bone marrow transcriptomics, cecal content 16S rRNA sequencing, and serum untargeted metabolomics were performed. Mice fed the FOS diet exhibited greater femoral trabecular bone volume and cortical bone thickness and area. FOS increased trabecular and cortical bone formation (i.e., periosteal and endocortical surface), and enhanced mineralization on the trabecular and endocortical surfaces. These changes coincided with increased osteoblasts and osteocytes, while osteoclasts were unchanged. Transcriptomics on the flushed femur revealed enrichment of pathways involving calcium ion homeostasis, PPAR signaling and adipogenesis, while in the bone marrow pathways associated with T-cell modulation and extracellular matrix organization were enriched. FOS altered the gut microbiota, increasing the abundance of taxa associated with fermentation and aromatic compound degradation, and increased serum metabolites (e.g., indole, mevalonate, polyphenol, and fatty acid intermediates). These findings reveal new insights into gut microbial and serum metabolite shifts induced with short-term FOS supplementation accompanying a rapid increase in osteocytes as well as bone formation and mineralization.

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