Vitamin D regulates the microbiota to induce optimal numbers of RORt/FoxP3+ regulatory T cells.

The active form of vitamin D (1,25(OH) 2 D) suppresses experimental models ofinflammatory bowel disease in part by regulating the microbiota. The role of vitamin D inthe regulation of microbe induced RORt/FoxP3+ T regs in the colon was determined.Vitamin D sufficient (D ) mice had significantly higher frequencies of FoxP3 T regsand RORt/FoxP3 T regs in the colon compared to vitamin D deficient (D−) mice. Thehigher frequency of RORt/FoxP3 T regs in D colon correlated with higher numbersof bacteria from the genus Clostridium XIVa and XVIII, and Bacteroides in D comparedto D- cecum. Transfer of the cecal bacteria from D or D- mice to germfree recipientsphenocopied the higher numbers of RORt/FoxP3 T regs in D versus D- recipientmice. The numbers of Clostridium XI, XIVa, and XVIII were correlated with thefrequencies of colonic RORt/FoxP3 T regs in the D and D- mice. D- mice with fewerRORt/FoxP3 T regs were significantly more susceptible to colitis than D mice.1,25D treatment of the D− mice beginning at 3 wks of age did not recoverRORt/FoxP3 T regs or the Clostridium XIVa and XVIII numbers to D values. Earlyvitamin D status shapes the microbiota to optimize the population of colonicRORt/FoxP3 T reg cells important for resistance to colitis.

维生素D的活性形式（1,25(OH)2D）通过调节微生物群的部分作用，抑制了实验性炎症性肠病的模型。本研究确定了维生素D在调节肠道微生物诱导的RORt/FoxP3+ Treg细胞方面的作用。维生素D充足（D+）小鼠的结肠中FoxP3 Treg和RORt/FoxP3 Treg的频率显著高于维生素D缺乏（D-）小鼠。D+小鼠结肠中RORt/FoxP3 Treg的频率较高，与Clostridium XIVa和XVIII以及Bacteroides的细菌数量增加相关，相比于D-回肠。将D+或D-小鼠的回肠细菌转移到无菌受体中，模拟了D+受体小鼠比D-受体小鼠中RORt/FoxP3 Treg数量更高的现象。Clostridium XI、XIVa和XVIII的数量与D+和D-小鼠结肠中RORt/FoxP3 Treg的频率相关。RORt/FoxP3 Treg数量较少的D-小鼠比D+小鼠对结肠炎的易感性显著增加。从3周龄开始对D-小鼠进行1,25D治疗，并未恢复RORt/FoxP3 Treg或Clostridium XIVa和XVIII的数量至D+水平。早期维生素D的状态塑造微生物群，以优化对抵抗结肠炎至关重要的结肠RORt/FoxP3 Treg细胞的种群。