Immunomodulatory effects of Vitamin D: Focus In the gut

SESSION 1 - EPIDEMIOLOGY - NUTRITIONAL PREVENTION AND CANCER RISKIntroduction:Vitamin D deficiency is observed in more than 80% of the elderly in France and is correlated with the appearance of pathophysiological processes related to aging (cancers and inflammatory diseases). Owing to the expression of its receptor (VDR) in immuno-competent cells (immune cells and barrier cells), vitamin D has the capacity to modulate innate and adaptive immune responses. The richness of intestinal tissue in immuno-competent cells (GALT: Gut Associated Lymphoid Tissue) makes this organ as a preferred target of the anti-inflammatory effects of vitamin D. Several epidemiological studies have yet established a correlation between vitamin D deficiency and the risk of developing a Chronic Inflammatory Bowel Disease and colorectal cancer.Objectives:This study aims to assess immunomodulatory effects of vitamin D in in the ileum of depleted and supplemented young and old rats.Methods:After 2 weeks acclimatization, 6 male Wistar rats aged 2 months and 8 rats aged 18 months were divided into 3 groups: Young control group (n = 6): 1 IU vitD / g diet; Elderly control group (n = 4): 1 IU vitD / g diet;- Elderly supplemented group (n = 4): 10 IU vitD / g diet.The rats were sacrificed after 3 months of diet and ileum was removed. These tissues were disrupted and subjected to a transcriptomic analysis targeted on genes of the metabolism of vitamin D and immunity in order to characterize the immune and inflammatory profile of intestine.Results:Our data demonstrated an overexpression of CYP24A1 with aging. This hydroxylases is known to inactivate vitamin D. Supplementation of vitamin D reduced its expression. Nevertheless, there was not significant difference of VDR expression between young and elderly rats, which remained at the same level after supplementation. mRNA expression levels of cathelicidin, IL6 and NFkB (p65) significantly increased in the elderly group. Supplementation of vitamin D significantly decreased expression of these pro-inflammatory molecules.Conclusion:Aging is accompanied by a majored degradation of active form of vitamin D and an inflammation status at the intestinal level. This inflammation could contribute to a major risk of carcinogenesis. Supplementation of vitamin D is able to limit the pathophysiological effects associated with aging, such as the appearance of low grade inflammatory status. A better understanding of the regulatory mechanisms induced by vitamin D in gut will enable us to acquire new knowledge useful in the prospects of a re-evaluation of the vitamin D requirements of the elderly population or even the systematic administration of a complementatio