B-vitamin deficiency is protective against DSS-induced colitis in mice
B-vitamin deficiency is protective against DSS-induced colitis in mice
复制标题
DOI：
10.1152/ajpgi.00076.2011
复制
发表时间：
2011-08-01
影响因子：
4.5
通讯作者：
Burrin, Douglas G.
中科院分区：
文献类型：
--
作者：
Benight, Nancy M.;Stoll, Barbara;Burrin, Douglas G.
Benight NM, Stoll B, Chacko S, da Silva VR, Marini JC, Gregory JF 3rd, Stabler SP, Burrin DG。b族维生素缺乏对dss诱导的小鼠结肠炎有保护作用。[J] .中国生物医学工程学报，2011,31(2):559 - 559。首次发表于2011年5月19日；doi: 10.1152 / ajpgi.00076.2011。维生素缺乏在炎症性肠病（IBD）患者中很常见。同型半胱氨酸（Hcys）是一种由蛋氨酸（Met）产生的致血栓氨基酸，IBD患者中其升高表明蛋氨酸代谢中断；然而，Hcys和Met代谢在IBD中的作用尚不清楚。我们假设缺乏b族维生素的饮食破坏Met代谢会加剧实验性结肠炎。小鼠分别饲喂缺乏b -6- b -12或对照组2周，然后用葡聚糖硫酸钠（DSS）诱导结肠炎。我们在DSS治疗期间监测疾病活动，并收集血浆和组织以分析炎症组织损伤和Met代谢物。我们还使用[1- c -13-甲基- h -2(3)]蛋氨酸输注类似处理的小鼠，通过测量体内Met动力学来量化Met循环活性。出乎意料的是，我们发现给予缺乏b族维生素饮食的小鼠具有改善的临床结果，包括增加存活率、体重维持和降低疾病评分。我们还发现，饮食不足小鼠的结肠中组织学疾病活动性和促炎基因（tnf - α和诱导型一氧化氮合酶）表达较低。代谢组学分析表明，这些影响与缺乏B-6有关，因为B-12功能的标记物仅轻度改变。体内蛋氨酸动力学证实了这些结果，表明缺乏饮食抑制转硫，但增加了再甲基化。我们的研究结果表明，由于B-6缺乏而导致的Met代谢紊乱会降低dss挑战小鼠的炎症反应和疾病活动。这些结果为进一步的人体临床研究提供了依据，以确定IBD患者B-6缺乏和Hcys升高是否与疾病病理生物学有关。
Benight NM, Stoll B, Chacko S, da Silva VR, Marini JC, Gregory JF 3rd, Stabler SP, Burrin DG. B-vitamin deficiency is protective against DSS-induced colitis in mice. Am J Physiol Gastrointest Liver Physiol 301: G249-G259, 2011. First published May 19, 2011; doi:10.1152/ajpgi.00076.2011.-Vitamin deficiencies are common in patients with inflammatory bowel disease (IBD). Homocysteine (Hcys) is a thrombogenic amino acid produced from methionine (Met), and its increase in patients with IBD indicates a disruption of Met metabolism; however, the role of Hcys and Met metabolism in IBD is not well understood. We hypothesized that disrupted Met metabolism from a B-vitamin-deficient diet would exacerbate experimental colitis. Mice were fed a B-6-B-12-deficient or control diet for 2 wk and then treated with dextran sodium sulfate (DSS) to induce colitis. We monitored disease activity during DSS treatment and collected plasma and tissue for analysis of inflammatory tissue injury and Met metabolites. We also quantified Met cycle activity by measurements of in vivo Met kinetics using [1-C-13-methyl-H-2(3)] methionine infusion in similarly treated mice. Unexpectedly, we found that mice given the B-vitamin-deficient diet had improved clinical outcomes, including increased survival, weight maintenance, and reduced disease scores. We also found lower histological disease activity and proinflammatory gene expression (TNF-alpha and inducible nitric oxide synthase) in the colon in deficient-diet mice. Metabolomic analysis showed evidence that these effects were associated with deficient B-6, as markers of B-12 function were only mildly altered. In vivo methionine kinetics corroborated these results, showing that the deficient diet suppressed transsulfuration but increased remethylation. Our findings suggest that disrupted Met metabolism attributable to B-6 deficiency reduces the inflammatory response and disease activity in DSS-challenged mice. These results warrant further human clinical studies to determine whether B-6 deficiency and elevated Hcys in patients with IBD contribute to disease pathobiology.