Altered tryptophan metabolism is associated with pediatric multiple sclerosis risk and course.
Altered tryptophan metabolism is associated with pediatric multiple sclerosis risk and course.
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DOI：
10.1002/acn3.637
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发表时间：
2018-10
影响因子：
5.3
通讯作者：
Waubant E
中科院分区：
文献类型：
--
作者：
Nourbakhsh B;Bhargava P;Tremlett H;Hart J;Graves J;Waubant E
确定色氨酸（Trp）代谢改变是否与儿童多发性硬化症风险或疾病严重程度相关。儿童发病多发性硬化症和临床孤立综合征（CIS）发病4年内的参与者和健康对照者进行了血清收集。收集病例的纵向残疾和处理速度测量以及复发数据。69/67例/对照组进行全球代谢组学研究。发现组（82例，50例对照）和验证组（92例，50例对照）进行了靶向色氨酸测定，17例进行了功能性肠道微生物组分析。采用调整后的logistic回归、线性和负二项回归以及Cox -比例风险模型。利用全球代谢组学数据，高相对丰度的色氨酸和吲哚乳酸（一种已知的肠道菌群衍生色氨酸代谢物）与ms的低风险相关。在某些情况下，高相对丰度的肠道菌群衍生色氨酸代谢物与较低的致残率和较高的处理速度评分相关，而高相对丰度的犬尿氨酸与较高的复发率相关。使用靶向色氨酸测量，在发现组和验证组中，血清色氨酸水平每增加1微克/毫升，分别与MS调整后的几率降低20% （95% CI: 4-34%）和32% （95% CI: 16-44%）相关。参与色氨酸分解代谢的肠道微生物基因相对丰度较低与较高的复发风险相关。肠道菌群和犬尿氨酸途径的色氨酸代谢可能与儿童多发性硬化症的风险以及多发性硬化症的活动和严重程度有关。
To determine if altered tryptophan (Trp) metabolism is associated with MS risk or disease severity in children. Participants with pediatric‐onset MS and clinically isolated syndrome (CIS) within 4 years of disease onset and healthy controls underwent collection of serum. Longitudinal disability and processing speed measures and relapse data were collected in cases. Global metabolomics were conducted in 69/67 cases/controls. Targeted Trp measurement was performed in a discovery group (82 cases, 50 controls) and a validation group (92 cases, 50 controls), while functional gut microbiome analysis was done in 17 cases. Adjusted logistic, linear and negative binomial regression and Cox‐proportional hazard models were used. Using global metabolomics data, higher relative abundances of Trp and indole lactate, a known gut microbiota‐derived Trp metabolite, were associated with lower risk of MS. In cases, higher relative abundances of gut microbiota‐derived Trp metabolites were associated with lower disability and higher processing speed scores and higher relative abundance of kynurenine was associated with higher relapse rate. Using targeted tryptophan measures, in the discovery and validation groups, each 1 mcg/mL increase in serum Trp level was associated with 20% (95% CI: 4–34%) and 32% (95% CI: 16–44%) decrease in adjusted odds of having MS, respectively. A lower relative abundance of gut microbial genes involved in Trp catabolism was associated with higher relapse risk. Trp metabolism by the gut microbiota and the kynurenine pathway may be relevant to the risk of MS in children as well as MS activity and severity.
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影响因子：
82.9
作者：
Rothhammer V;Mascanfroni ID;Bunse L;Takenaka MC;Kenison JE;Mayo L;Chao CC;Patel B;Yan R;Blain M;Alvarez JI;Kébir H;Anandasabapathy N;Izquierdo G;Jung S;Obholzer N;Pochet N;Clish CB;Prinz M;Prat A;Antel J;Quintana FJ
通讯作者：
Quintana FJ
影响因子：
11.2
作者：
Mowry, Ellen M.;Krupp, Lauren B.;Waubant, Emmanuelle
通讯作者：
Waubant, Emmanuelle
影响因子：
11.2
作者：
Polman CH;Reingold SC;Banwell B;Clanet M;Cohen JA;Filippi M;Fujihara K;Havrdova E;Hutchinson M;Kappos L;Lublin FD;Montalban X;O'Connor P;Sandberg-Wollheim M;Thompson AJ;Waubant E;Weinshenker B;Wolinsky JS
通讯作者：
Wolinsky JS
影响因子：
11.2
作者：
Fitzgerald KC;Munger KL;Hartung HP;Freedman MS;Montalbán X;Edan G;Wicklein EM;Radue EW;Kappos L;Pohl C;Ascherio A;BENEFIT Study Group
通讯作者：
BENEFIT Study Group
影响因子：
64.5
作者：
Farez MF;Mascanfroni ID;Méndez-Huergo SP;Yeste A;Murugaiyan G;Garo LP;Balbuena Aguirre ME;Patel B;Ysrraelit MC;Zhu C;Kuchroo VK;Rabinovich GA;Quintana FJ;Correale J
通讯作者：
Correale J