Written by Yuying Bai, Wei Song on behalf of the authors.

Fig. Mechanisms of gut-bone axis regulation in HIO and NO mice

Osteoporosis is the most prevalent chronic metabolic bone disease, which is characterized by decreased bone mass, microarchitectural deterioration, and increased bone fragility. ^1,2 The bone metabolism is influenced by many factors, such as genetics, hormones, age and nutrition, among which diet intervention is considered the safest and most easily implemented treatment to improve bone health. ^3-6

 A high-fat diet (HFD) has become a common dietary pattern in the worldwide. ^7,8 Recent studies suggest that an HFD not only leads to obesity but also induces metabolic abnormalities and absorption of bone. ^9-11 Although the relationship between obesity and bone loss is controversial, whether HFD alone preferentially drives bone loss with or without obesity and by what mechanism has not been studied.

 When we established a HFD model with BALB/c mice, we found that about 30% of the mice had constant weights and moved normally. This phenomenon caught our attention. Therefore, we regrouped the mice according to their body weight after 10 weeks of high-fat diet, HFD-induced obesity (HIO) mice were defined as having body weight higher than 20% of chow diet (CD) mice, while non-obese (NO) mice were defined as body weight within 5% of the CD weight range, and found that NO was protected from HIO-induced bone loss by the RANKL /OPG system, with associated increases in the tibia tenacity, cortical bone mean density, bone volume of cancellous bone, and trabecular number.

 The prominent changes in the gut microbiome analysis of SCFAs in the NO group pointed the way to investigate the mechanism. Subsequently, we performed SCFAs fed to HIO mice and fecal transfer experiments, results showed that SCFAs reversed the bone loss caused by HIO and HIO mice that received fecal microbiota from the NO group effectively reduced bone loss.

 These findings suggest that whether an HFD is good or bad diet for an individual is not decided by the dietary ingredients but by the individual’s gut microbiome, which may prove valuable for precisely tailoring nutrition strategies in the future.  

 Reference

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