The effect of flavan-3-ols on ovariectomy-induced bone loss in mice and the potential mechanisms

Flavan-3-ols (FLOs) have been reported to confer various health benefits, the majority of which reaching the colon for fermentation by gut microbiota. This study sought to examine the effects of FLOs on bone health and to evaluate the influence of gut microbiota on these effects. Using an ovariectomy-induced bone loss model in mice, the animals were administered either a low or high dose of FLOs, or a combination of FLOs with an antibiotic cocktail (Abs+FLOs). Compared to the control group, serum markers of bone formation, as well as bone quality as determined by micro-CT, were elevated in the groups supplemented with FLOs, particularly when combined with Abs. Furthermore, both FLOs and Abs+FLOs interventions significantly improved the levels of estrogen. However, no additional influence of FLOs on these markers was detected compared to the group supplemented with Abs alone. Analysis of 16S rRNA sequencing data revealed that the abundance of certain operational taxonomic units, such as s__unclassified_Clostridia_UCG_014, s__unclassified_Ruminococcus, and s__unclassified_Lachnospiraceae, was significantly reduced in osteoporotic mice but effectively reversed following the administration of FLOs. Transcriptomic analysis coupled with KEGG enrichment analysis indicated that Adrb3, Gdf10 (BMP3), Fosb, and Cxcl2, along with the PPARα/PGC-1/UCP1 signaling pathway, may potentially mediate the regulation of bone metabolism by flavanols. Collectively, the study uncovers the osteoprotective properties of flavan-3-ols, indicating that these effects may depend on the presence of gut microbiota.