Metabolomic analysis revealed that green tea polyphenols decreased - PowerPoint PPT Presentation

Metabolomic analysis revealed that green tea polyphenols decreased the formation of microbial metabolites of aromatic amino acids in humans Yuyin Zhou 1 , Ningning Zhang 1 , Andrea Arikawa 2 , and Chi Chen 1, * 1 Department of Food Science and Nutrition, University of Minnesota 1334 Eckles Ave, St Paul, MN 55108-1038 2 Department of Nutrition & Dietetics, University of North Florida 1 UNF Drive, Jacksonville, FL 32224-7699 * Corresponding author: chichen@umn.edu 1

Minn nnes esota Gr Green een T Tea Trial ( (MGTT) • Subjects: 120 postmenopausal women aged 50-70 years, with high mammographic density (>50% fibroglandular tissue). • Treatment: subjects taking green tea capsules (800 mg epigallocatechin gallate (EGCg)/day) or placebo for one year. • Sample group: --- P0 : placebo before trial --- P12 : placebo after trial --- T0 : GTPs treatment before the trial --- T12 : GTPs treatment after the trial • Urine and fecal samples were collected and analyzed by LC-MS-based metabolomics. LC-MS MDA https://clinicaltrials.gov/ct2/show/NCT00917735 2

Modeling of fecal and urine samples Urine s samples Fecal s samples P0 P12 T0 T12 T12 P0 P12 T0 3

Identification of GTP-responsive markers Fecal s samples Urine s samples Phenyl-acetylglutamine Hippuric acid Indoxyl sulfate Indole-3-carboxaldehyde 4

Identification of GTP microbial metabolite markers • A group of phenolic acids derived from microbial metabolism of GTPs were identified as the robust exposure markers. • Major GTPs were not found in significant amounts in feces. 5

Identification of GTP-responsive markers • Chronic GTPs treatment decreased the levels of microbial metabolites of aromatic amino acids in urine and feces. 6

• However, GTP treatment did not significantly affect the levels of short chain fatty acids and secondary bile acids, two other major groups of microbial metabolites. 7

Microbiome analysis (16S) 100% PCoA 80% 60% • Chronic GTP 40% did not change the microbial 20% composition. 0% T0 T12 OTU numbers Alpha diversity NA Verrucomicrobiae Thermoplasmata Synergistia Saccharimonadia Oxyphotobacteria Negativicutes Mollicutes Methanobacteria Melainabacteria Lentisphaeria Gammaproteobacteria T0 T12 T0 T12 8

Potential competitive inhibitions between microbial metabolism of GTPs and aromatic amino acids GTP Aromatic amino acids OH OH HO O Phenylalanine OH O Tryptophan OH OH O Tyrosine OH OH COOH OH OH COOH COOH OH OH Decarboxylation OH N HOOC OH HO H Dehydroxylation OH COOH COOH COOH HOOC HO OH CHO N Decarboxylation H N H OH COOH Indole-3- COOH HOOC HO OH carboxaldehyde Dehydroxylation Decarboxylation COOH Phenylacetyl- HO Indoxyl sulfate glutamine Dehydroxylation COOH 9 Hippuric acid

Conflict of interests The authors declare no conflict of interests. Acknowledgement This work was partially supported by the NIFA project No. MIN-18-092 . The human samples were from a NIH project 5R01CA127236-06. We thanks Dr. Hamed Samavat and Ms. Sarah Bedell for their assistance. Any questions, please email me. zhou0882@umn.edu 10