Appearance of green tea compounds in plasma following acute green tea consumption is modulated by the gut microbiome in mice

Study information

Reviewed Marked as Reviewed by Svetlana up on 2025-4-16

study design

laboratory experiment

Citation

PMID PubMed identifier for scientific articles.

39791884

DOI Digital object identifier for electronic documents.

10.1128/spectrum.01799-24

URI

Authors

Sterrett JD, Quinn KD, Doenges KA, Nusbacher NM, Levens CL, Armstrong ML, Reisdorph RM, Smith H, Saba LM, Kuhn KA, Lozupone CA, Reisdorph NA

Journal

Microbiology spectrum

Year

2025

Keywords:

16S RNA, food, gnotobiotic, metabolomics, microbiome, multi-omics, nutrition, polyphenols, symbiosis

UNLABELLED: Studies have suggested that phytochemicals in green tea have systemic anti-inflammatory and neuroprotective effects. However, the mechanisms behind these effects are poorly understood, possibly due to the differential metabolism of phytochemicals resulting from variations in gut microbiome composition. To unravel this complex relationship, our team utilized a novel combined microbiome analysis and metabolomics approach applied to low complexity microbiome (LCM) and human colonized (HU) gnotobiotic mice treated with an acute dose of powdered matcha green tea. A total of 20 LCM mice received 10 distinct human fecal slurries for an n = 2 mice per human gut microbiome; 9 LCM mice remained un-colonized with human slurries throughout the experiment. We performed untargeted metabolomics on green tea and plasma to identify green tea compounds that were found in the plasma of LCM and HU mice that had consumed green tea. 16S ribosomal RNA gene sequencing was performed on feces of all mice at study end to assess microbiome composition. We found multiple green tea compounds in plasma associated with microbiome presence and diversity (including acetylagmatine, lactiflorin, and aspartic acid negatively associated with diversity). Additionally, we detected strong associations between bioactive green tea compounds in plasma and specific gut bacteria, including associations between spiramycin and Gemmiger and between wildforlide and Anaerorhabdus. Notably, some of the physiologically relevant green tea compounds are likely derived from plant-associated microbes, highlighting the importance of considering foods and food products as meta-organisms. Overall, we describe a novel workflow for discovering relationships between individual food compounds and the composition of the gut microbiome. IMPORTANCE: Foods contain thousands of unique and biologically important compounds beyond the macro- and micro-nutrients listed on nutrition facts labels. In mammals, many of these compounds are metabolized or co-metabolized by the community of microbes in the colon. These microbes may impact the thousands of biologically important compounds we consume; therefore, understanding microbial metabolism of food compounds will be important for understanding how foods impact health. We used metabolomics to track green tea compounds in plasma of mice with and without complex microbiomes. From this, we can start to recognize certain groups of green tea-derived compounds that are impacted by mammalian microbiomes. This research presents a novel technique for understanding microbial metabolism of food-derived compounds in the gut, which can be applied to other foods.

Experiment 1

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Reviewed Marked as Reviewed by Svetlana up on 2025-4-16

Curated date: 2025/03/18

Curator: Jorie

Revision editor(s): Jorie, Ese, Ameenatoloko

Subjects

Location of subjects: United States of America

Host species Species from which microbiome was sampled. Contact us to have more species added.: Mus musculus

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Diet measurement Diet measurement,diet measurement

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Low complexity microbiome (LCM) mice

Group 1 name Corresponds to the case (exposed) group for case-control studies: Human colonized (HU) mice

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Mice were orally administered 200 μL of human fecal slurry (100 mg stool homogenized in 1 mL reduced phosphate-buffered saline [PBS]) at 4 weeks of age.

Group 0 sample size Number of subjects in the control (unexposed) group: 9

Group 1 sample size Number of subjects in the case (exposed) group: 20

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: log transformation

Statistical test: ANCOM-BC

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Alpha Diversity

Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample: increased

Signature 2

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Reviewed Marked as Reviewed by Svetlana up on 2025-4-16

Curated date: 2025/04/11

Curator: Ese

Revision editor(s): Ese, Ameenatoloko

Source: Within results text (Taxonomic composition of fecal microbiomes),Figure 2

Description: Taxonomic composition between Low Complexity Microbiome and Humanized Microbiome mice.

Abundance in Group 1: decreased abundance in Human colonized (HU) mice

NCBI	Quality Control	Links
Candidatus Epulonipiscium
Turicibacter
unclassified Peptostreptococcaceae

Revision editor(s): Ese, Ameenatoloko