Polyphenol Utilization Proteins in the Human Gut Microbiome

Abstract

Dietary polyphenols can significantly benefit human health, but their bioavailability is metabolically controlled by human gut microbiota. To facilitate the study of polyphenol metabolism for human gut health, we have manually curated experimentally characterized polyphenol utilization proteins (PUPs) from published literature. This resulted in 60 experimentally characterized PUPs (named seeds) with various metadata, such as species and substrate. Further database search found 107,851 homologs of the seeds from UniProt and UHGP (Unified Human Gastrointestinal Protein) databases. All PUP seeds and homologs were classified into protein classes, families and subfamilies based on Enzyme Commission (EC) numbers, Pfam (protein family) domains and sequence similarity networks. By locating PUP homologs in the genomes of UHGP, we have identified 1,074 physically linked PUP gene clusters (PGCs), which are potentially involved in polyphenol metabolism in the human gut. The gut microbiome of Africans was consistently ranked the top in terms of the abundance and prevalence of PUP homologs and PGCs among all geographical continents. This reflects the fact that dietary polyphenols are more commonly consumed by African population than other populations such as Europeans and North Americans. A case study of the Hadza hunter-gatherer microbiome verified the feasibility of using dbPUP to profile metagenomic data for biologically meaningful discovery, suggesting an association between diet and PUP abundance. A Pfam domain enrichment analysis of PGCs identified a number of putatively novel PUP families. Lastly, a user-friendly web interface ( https://bcb.unl.edu/dbpup/ ) provides all the data online to facilitate the research of polyphenol metabolism for improved human health. Importance Long-term consumption of polyphenol-rich foods have been shown to lower the risk of various human diseases such as cardiovascular diseases, cancers, and metabolic diseases. Raw polyphenols are often enzymatically processed by gut microbiome, which encode various polyphenol utilization proteins (PUPs) to produce metabolites with much higher bioaccessibility to gastrointestinal cells. This study delivered dbPUP as an online database for experimentally characterized PUPs and their homologs in human gut microbiome. This work also performed a systematic classification of PUPs into enzyme classes, families, and subfamilies. The signature Pfam domains were identified for PUP families, enabling conserved domain-based PUP annotation. This standardized sequence similarity-based PUP classification system offered a guideline for the future inclusion of new experimentally characterized PUPs and the creation of new PUP families. An in-depth data analysis was further conducted on PUP homologs and physically linked PUP gene clusters (PGCs) in gut microbiomes of different human populations.

CAMPER: curated annotations for profiling microbial polyphenol metabolic potential

“…These three genomes are a case study in the ability of CAMPER to identify and easily summarize genes for polyphenol metabolism in both well-studied and underexplored genomes, as well as control for false positive annotations. To obtain comparable data using existing annotation databases, we tried to annotate the same three genomes with kofamscan and dbPUP (Zheng et al 2022), another polyphenolfocused annotation database. Of the 7 enzymes, kofamscan and dbPUP included 3 and 2, respectively, in their database (Fig.…”

A Mixture of Pure, Isolated Polyphenols Worsens the Insulin Resistance and Induces Kidney and Liver Fibrosis Markers in Diet-Induced Obese Mice

“…The absorption of polyphenols depends on the dose and the type, and their effects are associated with their bioavailability and pharmacokinetics [ 14 ]. In the intestinal tract, they have shown limited stability and a low absorption rate, likely related to the microbiome which transforms the ingested polyphenols to their active metabolites [ 15 ]. Once absorbed, polyphenols are metabolized after their arrival in the liver via portal circulation.…”

Prune supplementation for 12 months alters the gut microbiome in postmenopausal women

“…1 While abundant in the fruit, chlorogenic acids are poorly absorbed in the upper intestine and become available to the gut microbiota in the lower intestine. The gut microbiota metabolize these compounds 12 to a diverse array of low molecular weight phenolic metabolites. 11,12 These microbial phenolic metabolites are more bioavailable to the host 13 and are believed to reduce the host inflammatory response 14 and inhibit development of inflammatory diseases.…”

“…The gut microbiota metabolize these compounds 12 to a diverse array of low molecular weight phenolic metabolites. 11,12 These microbial phenolic metabolites are more bioavailable to the host 13 and are believed to reduce the host inflammatory response 14 and inhibit development of inflammatory diseases.…”