Yang Jieping, Guo Yuanqiang, Lee Rupo, Henning Susanne M, Wang Jing, Pan Yajing, Qing Tianyu, Hsu Mark, Nguyen Alex, Prabha Siddarth, Ojha Rashi, Small Gary W, Heber David, Li Zhaoping
Center for Human Nutrition, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.
Curr Dev Nutr. 2020 Nov 25;4(11):nzaa165. doi: 10.1093/cdn/nzaa165. eCollection 2020 Nov.
We showed that pomegranate juice (PomJ) can help to maintain memory in adults aged >50 y. The mechanism for this effect is unknown, but might involve Trp and its metabolites, which are important in brain function.
We aimed to test the hypothesis that PomJ and its metabolites ellagic acid (EA) and urolithin A (UA) affect Trp metabolism.
Stool and plasma from a cohort [11 PomJ, 9 placebo drink (PL)] of subjects enrolled in our double-blind, placebo-controlled trial (NCT02093130) were collected at baseline and after 1 y of PomJ or PL consumption. In a mouse study, cecum and serum were collected from DBA/2J mice receiving 8 wk of dietary 0.1% EA or UA supplementation. Trp metabolites and intestinal microbiota were analyzed by LC-MS and 16S rRNA gene sequencing, respectively.
In the human study, the change in the plasma Trp metabolite indole propionate (IPA) over 1 y was significantly different between PomJ and PL groups (= 0.03). In serum of experimental mice, we observed a 230% increase of IPA by EA but not UA, a 54% increase of indole sulfate by UA but not EA, and 43% and 34% decreases of kynurenine (KYN) by EA and UA, respectively. In cecum, there was a 32% decrease of Trp by UA but not EA, and an 86% decrease of KYN by EA but not UA (< 0.05). The abundance of 2 genera, and , was reduced by PomJ in humans as well as by UA in mice, and their abundance was negatively associated with blood IPA in humans and mice (< 0.05).
These results suggest a novel mechanism involving the regulation of host and microbial Trp metabolism that might contribute to the health benefits of ellagitannins and EA-enriched food, such as PomJ.
我们发现石榴汁（PomJ）有助于维持50岁以上成年人的记忆力。这种作用的机制尚不清楚，但可能涉及色氨酸（Trp）及其代谢产物，它们对脑功能很重要。
我们旨在检验以下假设：PomJ及其代谢产物鞣花酸（EA）和尿石素A（UA）会影响色氨酸代谢。
在我们的双盲、安慰剂对照试验（NCT02093130）中，从一组受试者（11名饮用PomJ者，9名饮用安慰剂饮料（PL）者）收集基线期以及饮用PomJ或PL 1年后的粪便和血浆。在一项小鼠研究中，从接受8周0.1% EA或UA饮食补充的DBA/2J小鼠收集盲肠和血清。分别通过液相色谱-质谱联用（LC-MS）和16S rRNA基因测序分析色氨酸代谢产物和肠道微生物群。
在人体研究中，PomJ组和PL组血浆色氨酸代谢产物吲哚丙酸（IPA）在1年内的变化有显著差异（=0.03）。在实验小鼠的血清中，我们观察到EA使IPA增加230%，而UA无此作用；UA使硫酸吲哚增加54%，而EA无此作用；EA和UA分别使犬尿氨酸（KYN）减少43%和34%。在盲肠中，UA使色氨酸减少32%，而EA无此作用；EA使犬尿氨酸减少86%，而UA无此作用（<0.05）。在人体中，PomJ以及在小鼠中UA使两个菌属（ 和 ）的丰度降低，它们的丰度与人和小鼠血液中的IPA呈负相关（<0.05）。
这些结果提示了一种涉及宿主和微生物色氨酸代谢调节的新机制，这可能有助于解释鞣花单宁和富含EA的食物（如PomJ）对健康的益处。
