High Maternal Vitamin D Status <i>in utero</i> through Weaning Beneficially Affects the Gut Microbiota‐Bone Axis in Obese Male Mice

The gut microbiota may impact bone health via its released lipopolysaccharides (LPS), peptidoglycans or other metabolites, which we named the gut microbiota‐bone axis. A high‐fat high‐sugar diet increases serum LPS, decreases gut Bacteroides counts and weakens bones. In contrast, vitamin D has been recently shown to positively influence the composition of the gut microbiota, in addition to its important role in bone health. Interestingly, epidemiological studies show that prenatal vitamin D status is a critical contributor to offspring bone status. The purpose of this study was to investigate if exposure to high dietary vitamin D in utero and through weaning positively impacts gut microbiota and protects against chronic inflammation and compromised bone health in adult male mice fed a high‐fat high‐sugar diet. C57BL/6J dams were fed modified AIN93G containing high (H, 5000 IU/kg diet) or low (L, 25 IU/kg diet) vitamin D during pregnancy and lactation. At weaning, male pups remained on their respective vitamin D levels (HH or LL) or were switched (HL or LH) and fed a high‐fat high‐sugar diet to induce chronic inflammation. At seven months of age, colonic Bacteroides and serum LPS were quantified by quantitative PCR and ELISA and bone microarchitecture at the distal femur and lumbar vertebra 2 was assessed via micro computed tomography. Higher maternal but not offspring vitamin D status resulted in higher colonic Bacteroides counts (p=0.0004) and lower serum LPS (p=0.011) such that Bacteroides counts were negatively correlated with serum LPS (Spearman r=−0.49; p=0.018). Femur microarchitecture of offspring was also improved through higher maternal vitamin D status. Specifically, higher maternal vitamin D status resulted in offspring with higher bone volume/tissue volume (p=0.052), higher trabecular number (p=0.022) and lower trabecular separation (p=0.015) at distal femur and higher bone volume/tissue volume (p=0.049) at lumbar vertebra 2 compared to mothers with low vitamin D status. This suggests that the gut microbiota‐bone axis is programmed in utero and through weaning and is susceptible to nutritional modulation; the effects of low vitamin D status during these early life stages cannot completely be rescued by postnatal supplementation. Moreover, vitamin D may impact bone health via gut microbiota‐derived LPS. Support or Funding Information Funded by Centrum Foundation Research Innovation Fund, Department of Nutritional Sciences U of T, NSERC, Lawson Family Chair in Microbiome Nutrition Research, Banting and Best Diabetes Centre Novo Nordisk Studentship and Tamarack Graduate Award.

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