Effects of a high-fat diet on gut microbiota and possible implications for bone health in male Wistar rats.

Diet plays an important role in the composition of gut microbiota. Emerging research suggests that bone homeostasis can also be influenced by the gut microbiota. The aim of this study was to assess possible alterations in gut microbiota in an experimental obesity model induced by a high-fat diet (HFD) and the possible effects on parameters of bone metabolism and remodeling. Male Wistar rats were fed a HFD (60% lipids) or standard (control) diet for 14 weeks. Biochemical and hormonal parameters, bone histomorphometry, bone protein levels, and gut microbiota composition were analyzed. HFD animals exhibited a greater gut microbiota α-diversity represented by the Shannon Index and an increased relative abundance of the Proteobacteria phylum. Histomorphometry detected lower bone formation in the HFD group, accompanied by increased levels of serum and bone leptin and FGF-23 (fibroblast growth factor-23). The Shannon Index was correlated directly with bone FGF-23 (R 0.96, p = 0.04) and inversely with the osteoblastic surface (R -0.95, p = 0.04). The present study disclosed a significant increase in gut microbiota α-diversity and relative abundance of Proteobacteria phylum in obese animals fed a high-fat diet in parallel with increased levels of bone and serum leptin and FGF-23 and lower bone formation. The associations of Shannon Index with bone levels of FGF-23 and reduced osteoblastic surface suggest a link between HFD-induced higher gut microbiota diversity and low bone formation.