Polyphenol Utilization Proteins in the Human Gut Microbiome.
Polyphenol Utilization Proteins in the Human Gut Microbiome.
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DOI：
10.1128/aem.01851-21
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发表时间：
2022-02-08
影响因子：
4.4
通讯作者：
Yin Y
中科院分区：
文献类型：
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作者：
Zheng B;He Y;Zhang P;Huo YX;Yin Y
膳食多酚可以显着有益于人类健康，但其生物利用度是由人体肠道微生物群代谢控制的。为了促进多酚代谢对人类肠道健康的研究，我们从已发表的文献中手动策划了经过实验表征的多酚利用蛋白 (PUP)。这产生了 60 个经过实验表征的 PUP（称为种子），具有各种元数据，例如物种和基质。进一步的数据库搜索从 UniProt 和 UHGP（统一人类胃肠道蛋白）数据库中发现了 107,851 个种子的同源物。所有 PUP 种子和同源物均根据酶委员会 (EC) 编号、Pfam（蛋白质家族）结构域和序列相似性网络分为蛋白质类别、家族和亚家族。通过在 UHGP 基因组中定位 PUP 同源物，我们鉴定了 1,074 个物理连锁的 PUP 基因簇 (PGC)，它们可能参与人类肠道中的多酚代谢。就 PUP 同源物和 PGC 的丰度和流行率而言，非洲人的肠道微生物组在所有地理大陆中始终名列前茅。这反映了这样一个事实：非洲人群比欧洲人和北美人群等其他人群更常消耗膳食多酚。哈扎狩猎采集者微生物组的案例研究验证了使用 dbPUP 分析宏基因组数据以进行具有生物学意义的发现的可行性，表明饮食与 PUP 丰度之间存在关联。 Pfam 域富集 PGC 分析确定了许多假定的新型 PUP 家族。最后，用户友好的网络界面（https://bcb.unl.edu/dbpup/）在线提供所有数据，以促进多酚代谢研究以改善人类健康。重要性 长期食用富含多酚的食物已被证明可以降低多种人类疾病的风险，例如心血管疾病、癌症和代谢疾病。原始多酚通常由肠道微生物组进行酶促加工，其中含有各种多酚利用蛋白 (PUP)，以产生胃肠道细胞具有更高生物可及性的代谢物。这项研究将 dbPUP 作为在线数据库，用于记录人类肠道微生物组中经过实验表征的 PUP 及其同源物。这项工作还对 PUP 进行了系统分类，分为酶类、家族和亚家族。为 PUP 家族确定了签名 Pfam 域，从而实现基于保守域的 PUP 注释。这种标准化的基于序列相似性的 PUP 分类系统为未来纳入新的实验表征的 PUP 和创建新的 PUP 家族提供了指导。对不同人群肠道微生物组中 PUP 同源物和物理连接的 PUP 基因簇 (PGC) 进行了深入的数据分析。
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 consumed by the African population more commonly than by 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 has 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 contains 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.