Short-term dietary methionine supplementation affects one-carbon metabolism and DNA methylation in the mouse gut and leads to altered microbiome profiles, barrier function, gene expression and histomorphology.
Short-term dietary methionine supplementation affects one-carbon metabolism and DNA methylation in the mouse gut and leads to altered microbiome profiles, barrier function, gene expression and histomorphology.
复制标题
DOI：
10.1186/s12263-017-0576-0
复制
发表时间：
2017
影响因子：
3.5
通讯作者：
Koturbash I
中科院分区：
文献类型：
--
作者：
Miousse IR;Pathak R;Garg S;Skinner CM;Melnyk S;Pavliv O;Hendrickson H;Landes RD;Lumen A;Tackett AJ;Deutz NEP;Hauer-Jensen M;Koturbash I
蛋氨酸是一碳代谢的中心分子，是正常生长发育所必需的氨基酸。尽管蛋氨酸对生物系统很重要，但如果以超生理水平给药，它是有毒的。这项研究的目的是在小鼠模型中研究短期蛋氨酸饮食调节对空肠近端的影响，空肠近端是专门负责氨基酸吸收的肠道部分。8周龄CBA/J雄性小鼠饲喂蛋氨酸适量(MAD；6.5 mg/kg)或蛋氨酸补充(MSD；19.5 g/kg)日粮3.5天或6天(平均摄食量为100 mg/kg体重)。这项研究设计是为了解决西方人群中蛋氨酸饮食摄入量对应的蛋氨酸补充剂的短期影响。评估血液中的生化指标以及肠道中的代谢、表观遗传学、转录、后基因组和组织形态参数。到第6天，饲喂MSD(蛋白质摄入量与MAD相差10%)的小鼠血浆蛋氨酸浓度(p <； 0.054)升高了2.3倍，但空肠近端蛋氨酸浓度(p <； 0.0 5)降低了2.2倍，与中性氨基酸转运蛋白的表达无关。MSD还导致肠道细菌定植，增加了致病细菌伯克霍尔德雷亚斯的丰度，并降低了肠道跨膜蛋白Cldn8(0.18倍，p <； 0.05)、Cldn9(0.24倍，p <； 0.01)和Cldn10(0.05倍，p <； 0.05)的基因表达。饲喂MSD导致空肠近端组织形态发生显著变化，表现为血浆瓜氨酸浓度降低(1.80倍，p <； 0.07)，隐窝深度(减少28%，p <； 0.05)和粘膜表面(减少20%，p <； 0.001)。综上所述，这些变化表明，短期喂食MSD实质上改变了正常的肠道生理。这些效应可能参与肠道炎症性疾病的发病机制和/或使肠道对其他应激源敏感。本文的在线版本(10.1186/s12263-0170576-0)包含向授权用户提供的补充材料。
Methionine, a central molecule in one-carbon metabolism, is an essential amino acid required for normal growth and development. Despite its importance to biological systems, methionine is toxic when administered at supra-physiological levels. The aim of this study was to investigate the effects of short-term methionine dietary modulation on the proximal jejunum, the section of the gut specifically responsible for amino acid absorption, in a mouse model. Eight-week-old CBA/J male mice were fed methionine-adequate (MAD; 6.5 g/kg) or methionine-supplemented (MSD; 19.5 g/kg) diets for 3.5 or 6 days (average food intake 100 g/kg body weight). The study design was developed in order to address the short-term effects of the methionine supplementation that corresponds to methionine dietary intake in Western populations. Biochemical indices in the blood as well as metabolic, epigenetic, transcriptomic, metagenomic, and histomorphological parameters in the gut were evaluated. By day 6, feeding mice with MSD (protein intake <10% different from MAD) resulted in increased plasma (2.3-fold; p < 0.054), but decreased proximal jejunum methionine concentrations (2.2-fold; p < 0.05) independently of the expression of neutral amino acid transporters. MSD has also caused small bowel bacteria colonization, increased the abundance of pathogenic bacterial species Burkholderiales and decreased the gene expression of the intestinal transmembrane proteins—Cldn8 (0.18-fold, p < 0.05), Cldn9 (0.24-fold, p < 0.01) and Cldn10 (0.05-fold, p < 0.05). Feeding MSD led to substantial histomorphological alterations in the proximal jejunum exhibited as a trend towards decreased plasma citrulline concentrations (1.8-fold, p < 0.07), as well as loss of crypt depth (by 28%, p < 0.05) and mucosal surface (by 20%, p < 0.001). Together, these changes indicate that short-term feeding of MSD substantially alters the normal gut physiology. These effects may contribute to the pathogenesis of intestinal inflammatory diseases and/or sensitize the gut to exposure to other stressors. The online version of this article (10.1186/s12263-017-0576-0) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
4.9
作者：
Bao W;Kojima KK;Kohany O
通讯作者：
Kohany O
影响因子：
5.1
作者：
Batra, Vipen;Sridhar, Swathi;Devasagayam, Thomas Paul Asir
通讯作者：
Devasagayam, Thomas Paul Asir
影响因子：
3.7
作者：
Clifford RJ;Milillo M;Prestwood J;Quintero R;Zurawski DV;Kwak YI;Waterman PE;Lesho EP;Mc Gann P
通讯作者：
Mc Gann P
影响因子：
3.5
作者：
Camilleri M;Madsen K;Spiller R;Greenwood-Van Meerveld B;Verne GN
通讯作者：
Verne GN
影响因子：
2
作者：
BADDELEY, AJ;GUNDERSEN, HJG;CRUZORIVE, LM
通讯作者：
CRUZORIVE, LM