Dataset Information

Pomegranate Metabolites Impact Tryptophan Metabolism in Humans and Mice.

ABSTRACT: Background: 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.

Objectives: We aimed to test the hypothesis that PomJ and its metabolites ellagic acid (EA) and urolithin A (UA) affect Trp metabolism.

Methods: 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.

Results: 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 (P = 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 (P < 0.05). The abundance of 2 genera, Shigella and Catenibacterium, 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 (P < 0.05).

Conclusions: 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.

SUBMITTER: Yang J

PROVIDER: S-EPMC7695807 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Pomegranate Metabolites Impact Tryptophan Metabolism in Humans and Mice.

Yang Jieping J Guo Yuanqiang Y Lee Rupo R Henning Susanne M SM Wang Jing J Pan Yajing Y Qing Tianyu T Hsu Mark M Nguyen Alex A Prabha Siddarth S Ojha Rashi R Small Gary W GW Heber David D Li Zhaoping Z

Current developments in nutrition 20201125 11

<h4>Background</h4>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.<h4>Objectives</h4>We aimed to test the hypothesis that PomJ and its metabolites ellagic acid (EA) and urolithin A (UA) affect Trp metabolism.<h4>Methods</h4>Stool and plasma from a cohort [11 PomJ, 9 placebo drink (PL)] of subjects enrolled in our double-blind, place ...[more]

PMID: 33274309

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Project description:It is increasingly recognized that psychological stress influences inflammatory responses and mood. Here, we investigated whether psychological stress (combined acoustic and restraint stress) activates the tryptophan (Trp) catabolizing enzyme indoleamine 2,3-dioxygenase 1(IDO1) and thereby alters the immune homeostasis and behavior in mice. We measured IDO1 mRNA expression and plasma levels of Trp catabolites after a single 2-h stress session and in repeatedly stressed (4.5-days stress, 2-h twice a day) naïve BALB/c mice. A role of cytokines in acute stress-induced IDO1 activation was studied after IFNgamma and TNFalpha blockade and in IDO1(-/-) mice. RU486 and 1-Methyl-L-tryptophan (1-MT) were used to study role of glucocorticoids and IDO1 on Trp depletion in altering the immune and behavioral response in repeatedly stressed animals. Clinical relevance was addressed by analyzing IDO1 activity in patients expecting abdominal surgery. Acute stress increased the IDO1 mRNA expression in brain, lung, spleen and Peyer's patches (max. 14.1+/-4.9-fold in brain 6-h after stress) and resulted in a transient depletion of Trp (-25.2+/-6.6%) and serotonin (-27.3+/-4.6%) from the plasma measured 6-h after stress while kynurenine levels increased 6-h later (11.2+/-9.3%). IDO1 mRNA up-regulation was blocked by anti-TNFalpha and anti-IFNgamma treatment. Continuous IDO1 blockade by 1-MT but not RU486 treatment normalized the anti-bacterial defense and attenuated increased IL-10 inducibility in splenocytes after repeated stress as it reduced the loss of body weight and behavioral alterations. Moreover, kynurenic acid which remained increased in 1-MT treated repeatedly stressed mice was identified to reduce the TNFalpha inducibility of splenocytes in vitro and in vivo. Thus, psychological stress stimulates cytokine-driven IDO1 activation and Trp depletion which seems to have a central role for developing stress-induced immunosuppression and behavioral alteration. Since patients showed Trp catabolism already prior to surgery, IDO is also a possible target enzyme for humans modulating immune homeostasis and mood.

Dataset Information

Pomegranate Metabolites Impact Tryptophan Metabolism in Humans and Mice.

Publications

Pomegranate Metabolites Impact Tryptophan Metabolism in Humans and Mice.

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