Luthold Renata V, Fernandes Gabriel R, Franco-de-Moraes Ana Carolina, Folchetti Luciana G D, Ferreira Sandra Roberta G
Department of Nutrition, School of Public Health, University of São Paulo, SP, Brazil.
Oswaldo Cruz Foundation, René Rachou Research Center, Belo Horizonte, MG, Brazil.
Metabolism. 2017 Apr;69:76-86. doi: 10.1016/j.metabol.2017.01.007. Epub 2017 Jan 13.
Due to immunomodulatory properties, vitamin D status has been implicated in several diseases beyond the skeletal disorders. There is evidence that its deficiency deteriorates the gut barrier favoring translocation of endotoxins into the circulation and systemic inflammation. Few studies investigated whether the relationship between vitamin D status and metabolic disorders would be mediated by the gut microbiota composition.
We examined the association between vitamin D intake and circulating levels of 25(OH)D with gut microbiota composition, inflammatory markers and biochemical profile in healthy individuals.
In this cross-sectional analysis, 150 young healthy adults were stratified into tertiles of intake and concentrations of vitamin D and their clinical and inflammatory profiles were compared. The DESeq2 was used for comparisons of microbiota composition and the log2 fold changes (log2FC) represented the comparison against the reference level. The association between 25(OH)D and fecal microbiota (16S rRNA sequencing, V4 region) was tested by multiple linear regression.
Vitamin D intake was associated with its concentration (r=0.220, p=0.008). There were no significant differences in clinical and inflammatory variables across tertiles of intake. However, lipopolysaccharides increased with the reduction of 25(OH)D (p-trend <0.05). Prevotella was more abundant (log2FC 1.67, p<0.01), while Haemophilus and Veillonella were less abundant (log2FC -2.92 and -1.46, p<0.01, respectively) in the subset with the highest vitamin D intake (reference) than that observed in the other subset (first plus second tertiles). PCR (r=-0.170, p=0.039), E-selectin (r=-0.220, p=0.007) and abundances of Coprococcus (r=-0.215, p=0.008) and Bifdobacterium (r=-0.269, p=0.001) were inversely correlated with 25(OH)D. After adjusting for age, sex, season and BMI, 25(OH)D maintained inversely associated with Coprococcus (β=-9.414, p=0.045) and Bifdobacterium (β=-1.881, p=0.051), but significance disappeared following the addition of inflammatory markers in the regression models.
The role of vitamin D in the maintenance of immune homeostasis seems to occur in part by interacting with the gut microbiota. The attenuation of association of bacterial genera by inflammatory markers suggests that inflammation participate in part in the relationship between the gut microbiota and vitamin D concentration. Studies with appropriate design are necessary to address hypothesis raised in the current study.
由于具有免疫调节特性，维生素D状态已被认为与骨骼疾病以外的多种疾病有关。有证据表明，维生素D缺乏会破坏肠道屏障，有利于内毒素进入循环系统并引发全身炎症。很少有研究调查维生素D状态与代谢紊乱之间的关系是否由肠道微生物群组成介导。
我们研究了健康个体中维生素D摄入量和25(OH)D循环水平与肠道微生物群组成、炎症标志物和生化指标之间的关联。
在这项横断面分析中，150名年轻健康成年人按维生素D摄入量和浓度分为三个三分位数组，并比较了他们的临床和炎症指标。使用DESeq2比较微生物群组成，log2倍变化（log2FC）表示与参考水平的比较。通过多元线性回归测试25(OH)D与粪便微生物群（16S rRNA测序，V4区域）之间的关联。
维生素D摄入量与其浓度相关（r=0.220，p=0.008）。摄入量三分位数组之间的临床和炎症变量无显著差异。然而，脂多糖随着25(OH)D的降低而增加（p趋势<0.05）。在维生素D摄入量最高的亚组（参考组）中，普雷沃氏菌更为丰富（log2FC 1.67，p<0.01），而嗜血杆菌和韦荣球菌则较少（log2FC分别为-2.92和-1.46，p<0.01），与其他亚组（第一和第二个三分位数组）相比。PCR（r=-0.170，p=0.039）、E选择素（r=-0.220，p=0.007）以及粪球菌（r=-0.215，p=0.008）和双歧杆菌（r=-0.269，p=0.001）的丰度与25(OH)D呈负相关。在调整年龄、性别、季节和BMI后，25(OH)D与粪球菌（β=-9.414，p=0.045）和双歧杆菌（β=-1.881，p=0.051）仍呈负相关，但在回归模型中加入炎症标志物后，这种相关性消失。
维生素D在维持免疫稳态中的作用似乎部分是通过与肠道微生物群相互作用实现的。炎症标志物减弱了细菌属之间的关联，这表明炎症在肠道微生物群与维生素D浓度之间的关系中也起到了一定作用。需要进行适当设计的研究来验证本研究中提出的假设。
