EFFECTS OF DIET ALTERATIONS, WITH OR WITHOUT FECAL MICROBIAL TRANSPLANTS, ON BONE INTEGRITY

Abstract

High fat feeding exerts a negative impact on bone quality and strength. Gut microbiota have been strongly linked to bone outcomes in several models, though a clear mechanism linking alterations in gut microbiota, diet composition, and bone has not yet been elucidated. PURPOSE: To determine if alterations in diet, with or without fecal microbial transplants (FMT) can rescue bone integrity in diet-induced obesity. METHODS: 6-wk old male C57Bl/6 mice (n=10/group) were randomized to a low-fat (LF) or high fat, high sugar (HFS) diet ad libitum for 13 wks. HFS mice were randomized to one of three groups for 4 wks: LF diet with FMT from the LF mice (HFS/LF+), LF diet with sham FMT using PBS (HFS/LF), or HFS diet with FMT from the LF mice (HFS/HFS+) to simulate the impact of combined diet alteration and addition of “healthy” microbes, diet alterations only, and addition of “healthy” microbes only, respectively. Animals had free access to a running wheel until terminated at 23 wks of age. Statistical analyses were performed using a two-way ANOVA and Tukey’s post-hoc test. RESULTS: HFS/HFS+ mice showed greater absolute femoral neck (FN) strength versus HFS/LF and HFS/LF+ mice (p<0.003), while LF/LF mice had the greatest relative FN strength versus all groups (p<0.016). Whole femur bone mineral density (BMD, g/cm2) was greater in HFS/HFS+ versus all groups (p<0.023); LF/LF mice had the highest BMD when normalized to body weight (p<0.029). Immunostaining for tumor necrosis factor alpha, sclerostin, insulin-like growth factor 1, and interferon gamma in cortical and cancellous bone revealed no differences between groups. Despite no difference in marrow adipocyte number (#/mm2) between groups, HFS/HFS+ mice had greater marrow adipocyte size (μm2) versus LF/LF mice; diet alteration, with and without transplanted “healthy” microbes, was able to partially attenuate increased marrow adipocyte size. CONCLUSIONS: A change in diet from HFS to LF led to reduced absolute FN strength compared to HFS/HFS+ and LF/LF mice, with no apparent effect from transplanted “healthy” gut microbes. LF/LF mice had greater relative femoral neck strength. Altering diet, with and without FMT’s, was sufficient to partially rescue the detrimental impacts of high fat, high sugar feeding on bone integrity.