Abstract

Inflammatory bowel disease (IBD) is an idiopathic disease that can impair bone metabolism. Low vitamin D status has been implicated in its progress. This study used interleukin (IL)-10 knockout (KO) mice, that develop an intestinal inflammation when housed in a non-sterile environment, to determine if supplementation with vitamin D3 throughout life could mitigate inflammation and attenuate the lower bone mineral content (BMC) and density (BMD), and bone strength. Female IL-10 KO mice were randomized 25 or 5000 IU vitamin D3/kg diet throughout pregnancy and lactation. At weaning, offspring received the same or opposite diet as their mother until age three months. Body weight growth was similar among groups within a sex. At three months of age, there were no differences in inflammation and gene expression in the colon of offspring. Male offspring exposed to continuous 25 IU vitamin D3/kg diet had lower (p < 0.001) colonic VDR expression and those exposed only to low vitamin D3 until weaning had higher serum IL-6. There were no differences in femur or vertebral BMC, BMD or bone strength. In summary, long-term exposure to vitamin D3 did not attenuate intestinal inflammation or preserve bone mineral or bone strength. Thus, supplementation with vitamin D3 does not exert anti-inflammatory effects in this mouse model that mimics human inflammatory bowel disease.

Highlights

  • Inflammatory bowel disease (IBD) is an idiopathic disease comprising Crohn’s disease and ulcerative colitis, characterized by a dysregulated immune response towards the normal intestinal microbiota in genetically susceptible people [1]

  • The objective of this study was to determine if lifelong supplementation with vitamin D3 in utero and through to three months of age could mitigate the development of intestinal inflammation and subsequent bone abnormalities in IL-10 KO offspring at young adulthood

  • There were no significant differences in litter size (H: 6 ± 0 pups, L: 6 ± 0 pups, p = 0.51) or pup weight at postnatal day (PND) 14 (H: 6.9 ± 0.3 g, L: 6.7 ± 0.2 g, p = 0.43) between high and low vitamin D groups

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Summary

Introduction

Inflammatory bowel disease (IBD) is an idiopathic disease comprising Crohn’s disease and ulcerative colitis, characterized by a dysregulated immune response towards the normal intestinal microbiota in genetically susceptible people [1]. This results in the production of proinflammatory cytokines, such as interferon-γ (IFN-γ), interleukin-1α (IL-1α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-17. The objective of this study was to determine if lifelong supplementation with vitamin D3 in utero and through to three months of age could mitigate the development of intestinal inflammation and subsequent bone abnormalities (lower BMC, BMD and bone strength) in IL-10 KO offspring at young adulthood

Animals and Diet
Litter Characteristics and Body Weight
Histological Assessment
RNA Extraction
Microarray Analysis
Colonic VDR Expression
Cytokine and Bone Marker Analysis
2.10. Statistical Analyses
Colonic Gene Expression
Cytokine Analysis
Serum Bone Markers and Femur and Lumbar Vertebrae Outcomes
Discussion
Conclusions

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