Dietary vitamin B6 intake modulates colonic inflammation in the IL10-/- model of inflammatory bowel disease.

Pyridoxal-5-phosphate, the biologically active form of vitamin B6, is a cofactor for over 140 biochemical reactions. Although severe vitamin B6 deficiency is rare, mild inadequacy [plasma pyridoxal 5’-phosphate (PLP) <20 nmol/L] is observed in 19–27% of the US population. Plasma PLP concentrations are inversely related to markers of inflammation such as C-reactive protein. Furthermore, plasma PLP is diminished in those with inflammatory conditions and, in the case of inflammatory bowel disease (IBD), more so in those with active versus quiescent disease. Restricting B6 intake attenuates IBD pathology in mice; however, the effects of supplementation are unclear. We therefore sought to determine the effects of mild inadequacy and moderate supplementation of B6 on the severity of colonic inflammation. Weanling IL-10−/− (positive for Helicobacter hepaticus) mice were fed diets containing 0.5 (deficient), 6.0 (replete) or 24 (supplemented) mg/kg pyridoxine HCl for 12 weeks and then assessed for histological and molecular markers of colonic inflammation. Both low and high plasma PLP were associated with a significant suppression of molecular (TNFα, IL-6, IFN-γ, COX-2 and iNOS expression) and histological markers of inflammation in the colon. PLP is required for the breakdown of sphingosine 1-phosphate (S1P), a chemotactic lipid, by S1P lyase. Colonic concentrations of S1P and PLP were significantly and inversely correlated. If confirmed, vitamin B6 supplementation may offer an additional tool for the management of IBD. Although B6 is required in dozens of reactions, its role in the breakdown of S1P may explain the biphasic relationship observed between PLP and inflammation.

吡哆醛 - 5 - 磷酸是维生素B6的生物活性形式，是140多种生化反应的辅因子。尽管严重的维生素B6缺乏症很少见，但在美国人群中，有19% - 27%的人存在轻度缺乏（血浆吡哆醛5’ - 磷酸（PLP）<20 nmol/L）的情况。血浆PLP浓度与炎症标志物如C - 反应蛋白呈负相关。此外，患有炎症疾病的患者血浆PLP水平会降低，就炎症性肠病（IBD）而言，活动期患者比缓解期患者的血浆PLP水平更低。限制B6摄入会减轻小鼠的IBD病理状况；然而，补充B6的效果尚不清楚。因此，我们试图确定B6轻度缺乏和适度补充对结肠炎症严重程度的影响。给断奶的白细胞介素 - 10基因敲除（肝螺杆菌阳性）小鼠喂食含0.5（缺乏）、6.0（充足）或24（补充）mg/kg盐酸吡哆醇的饲料，持续12周，然后评估结肠炎症的组织学和分子标志物。低血浆PLP和高血浆PLP都与结肠中分子（肿瘤坏死因子α、白细胞介素 - 6、干扰素 - γ、环氧合酶 - 2和诱导型一氧化氮合酶表达）和炎症组织学标志物的显著抑制有关。PLP是鞘氨醇 - 1 - 磷酸（S1P）裂解酶分解趋化性脂质S1P所必需的。结肠中S1P和PLP的浓度呈显著负相关。如果得到证实，维生素B6补充剂可能为IBD的治疗提供一种额外的手段。尽管B6在数十种反应中是必需的，但其在S1P分解中的作用可能解释了PLP与炎症之间观察到的双相关系。