Pomegranate Metabolites Impact Tryptophan Metabolism in Humans and Mice

Abstract

Background We showed that pomegranate juice (PomJ) may help to maintain memory in adults older than 50 years of age. The mechanism for this effect is unknown, but may involve tryptophan (Trp) and its metabolites, which are important in brain function. Objectives We aim 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) of subjects enrolled in our double-blind, placebo-controlled trial (NCT02093130) were collected at baseline and after 1 year of PomJ or placebo drink (PL) consumption. In mice, cecum and serum were collected from DBA2J mice receiving 8-weeks’ dietary 0.1% EA or UA supplementation. Trp metabolites and intestinal microbiota were analyzed by liquid chromatography–mass spectrometry and 16S rRNA gene sequencing respectively. Results In the human study, the change in plasma Trp metabolite indole propionate (IPA) over one year was significantly different between PomJ and PL groups (P = 0.03). In serum of experimental mice, we observed 230% increase of IPA by EA but not UA, 54% increase of IS by UA but not EA, and 43% and 34% decrease of kynurenine (KYN) by EA and UA respectively. In cecum, there were 32% decrease of Trp by UA but not EA and 86% decrease of KYN by EA but not UA (P < 0.05). The abundance of two 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). Conclusion These results suggest a novel mechanism involving the regulation of host and microbial Trp metabolism that may contribute to the health benefits of ellagitannins and EA enriched food, such as PomJ.

Effect of Standardized Grape Powder Consumption on the Gut Microbiome of Healthy Subjects: A Pilot Study

“…Beta diversity was calculated using Bray-Curtis dissimilarity. The relationships of samples across groups were determined by permutational multivariate analysis of variance (PERMANOVA) using the Adonis command provided by Vegan in R and were displayed via principal coordinate analysis (PCoA) ordination [14]. DESeq2 was used to identify abundance changes at the genus level and differences that occurred between the baseline, week 4 samples, and week 8 samples following the grape powder intervention.…”

“…DESeq2 was used to identify abundance changes at the genus level and differences that occurred between the baseline, week 4 samples, and week 8 samples following the grape powder intervention. A statistical model (formula: ~subject + treatment) was passed to DESeq2, which permitted accounting for differences between subjects while estimating the effect due to the treatment [12,14]. p-values were adjusted for multiple testing using Benjamini-Hochberg false discovery rate correction in DESeq2.…”

Pomegranate Extract Improves Colitis in IL‐10 Knockout Mice Fed a High Fat High Sucrose Diet

“…[ 50 ] We recently showed that pomegranate juice intake significantly affects microbial Trp metabolism and host inflammatory markers. [ 51 ] Here, significantly higher fecal IPA and lower blood Kyn to Trp ratio were observed in PomX fed mice compared with HFHS mice. Interestingly, our RNAseq data showed that Ido2 was significantly downregulated by PomX.…”

“…Colonic and serum levels of Trp and its major metabolites, indole‐2‐acetic acid (IAA), kynurenine (KYN), kynurenic acid (KYA), indole‐3‐propionatic acid (IPA), and Indole sulfate (IS), were determined using Liquid chromatography coupled to electrospray ionization triple quadrupole mass spectrometry (LC‐ESI‐MS/MS) and HPLC florescence as previously described. [ 51 ]…”

“…The significance of beta diversity differences across groups were determined by Permutational Multivariate Analysis of Variance (PERMANOVA) using the Adonis command provided by Vegan in R. DESeq2 was used to identify differentially abundant genera between HFHS/PomX mice and HFHS mice using model (∼ treatment) and to assess for significant associations of microbial genera with colitis score using model (∼histological score). [ 51 ]…”