Are (poly)phenols able to improve nutritional status? Can they assist in the prevention of human diseases? Although most researchers in the field would answer affirmatively to both questions without major discussion, (poly)phenol research is still considered a minor part of nutrition sciences. Despite the scientific community, policymakers and even consumers being aware of their potential health benefits, the presence (poly)phenols in dietary guidelines, and sound nutritional strategies is still very limited. However, there is enough evidence to believe that they can be valuable assets to improve the nutritional status of an individual, even to reduce the risk of suffering from some major chronic diseases. However, this evidence is not enough to play in the major leagues. (Poly)phenols are not essential, comprise a very broad family of chemical structures, present a complex metabolism, and are widespread in plant-based food and drinks. Not all (poly)phenols are the same and they are everywhere, while they are prone to high inter-individual variation rates both in the metabolism and the physiological response associated with their consumption. These characteristics may seem drawbacks for these phytochemicals as health-promoting compounds. The current nutritional paradigm deals mainly with nutrients, molecules considered essential and able to impact physiological processes.

(Poly)phenols are non-nutrients, but they are also able to drive physiological responses. Perhaps they deserve a more crucial role in the actual nutritional scenario, where prevention of diseases by an excess of nutrients represents the main challenge. Their recognition as food bioactives able to improve human health needs realistic, robust, and reliable insights. This Special Issue gathers a series of original research articles and reviews demonstrating the importance of (poly)phenols for human nutrition. They provide invaluable contributions to the research front and may serve to goad the scientific community to build a new paradigm including not only nutrients, but all the biologically active molecules present in food.

The effects of (poly)phenols on human health are pleiotropic, and interesting findings related to different body systems have been published. The cardiovascular scenario has been widely assessed in the (poly)phenol literature, while the influence of the biological rhythms on the protective effects of dietary (poly)phenols has not been considered in any detail. The review by Torres-Fuentes et al.^[1] addresses this topic, discussing the contribution of both circadian and seasonal rhythms to the effects of (poly)phenols, and deepening in the importance of factors that are not commonly taken into account. Milenkovic et al.^[2] evaluated the nutrigenomic and nutriepigenomic effects of cocoa flavan-3-ols in middle-age men. Preservation of the integrity of immunological-endothelial barrier functions may be one of the molecular mechanisms behind the well-known protective role of these flavonoids in vascular health. Non-significant results are also of interest to better understand the compounds having an effect on key biomarkers of cardiometabolic risk. In this sense, Aboufarrag et al.^[3] report that anthocyanin extracts from bilberry and black rice did not affect lipoprotein profiles, functions, or glycemic control in a randomized, placebo-controlled, crossover trial with hyperlipidemic participants. The review by Williamson^[4] supports previous results on the weak effects of anthocyanins on glucose homeostasis, while it provides a complete and mechanistic overview of how many dietary (poly)phenols may inhibit glucose transporters and modulate glucose uptake. A very interesting read.

Intestinal health represents an important research topic for (poly)phenols. Taladrid et al.^[5] conduced an explorative trial assessing the impact of moderate red wine consumption on the clinical status and symptomatology of patients with an active-phase ulcerative colitis. Besides fecal microbiota, they studied saliva microbiota, as oral dysbiosis may also play a role in this gut disease. In Caco-2 cell monolayers, Iglesias et al.^[6] also addressed the capacity of a polyphenol, curcumin, in mitigating intestinal barrier inflammation and oxidative stress and preserving monolayer integrity. Rubert et al.^[7] screened dietary (poly)phenols and their gut microbiota-related metabolites in the context of colorectal cancer, using 3D HCT116 spheroids. An optimized high-throughput imaging approach was used and some phenyl-γ-valerolactones and phenolic acids were able to inhibit spheroid aggregation. Spheroids were also used by Carecho et al.^[8] to demonstrate the neuroprotective effects of two phenolic metabolites that are able to cross the blood-brain barrier on a human 3D cell model of Parkinson's disease. This further supports the role of (poly)phenol metabolites in brain (patho)physiology. In this regard, Cheng et al.^[9] provided evidence for the positive impact of flavonoids on human cognition through a meta-analysis of randomized controlled trials with subgroup analysis.

The importance of (poly)phenol metabolism by gut microbiota and how this may condition their health effects have also been addressed. Koistinen et al.^[10] identified a pattern of phenolic catabolites, produced both from Lactiplantibacillus plantarum-fermented rye and during colonic fermentation, that was able to synergistically modulate bacterial growth. García-Villalba et al.^[11] provide a comprehensive review on the metabolism, associated gut microbiota, and bioactivity of urolithins, colonic metabolites derived from ellagitannins and ellagic acid. Di Pede et al.^[12] assess the influence of flavan-3-ol structure on the production of phenolic catabolites using an in vitro fecal fermentation model. Insights on the catabolic pathways of 12 monomeric flavan-3-ols and procyanidins and the stoichiometry associated with the production of bioactive catabolites are provided. Future research should also include a focus on the effect of (poly)phenols on gut microbiota and the production of bioactive metabolites. Research by Peron et al.^[13] shows how a (poly)phenol-rich diet in older adults was able to increase serum indole 3-propionic acid.

Two mandatory articles for anyone in the field of (poly)phenol analysis, and not just beginners, were masterly produced by Kuhnert and Clifford.^[14] One addresses a “practitioner's dilemma” in mass spectrometry annotation and identification of (poly)phenol metabolites, while its companion review drew attention to pitfalls on the LC–MS characterization and quantification of (poly)phenols, suggesting strategies for their avoidance.^[15] The article by Kay's group,^[16] presents a dietary exposome library including host and gut microbiome metabolites for use in peak identification/annotation of untargeted metabolomics datasets. This a good practical example and further supports the need for good analytical practices to better understand the journey of (poly)phenols in human body.

This frontier science described in this Special Issue may pave the way for future realistic, reliable, and robust interventions and analytical approaches. We acknowledge all the authors, most of them good friends, for their valuable contributions. We hope the scientific community will enjoy reading them as much as we did and together let's shape the future of (poly)phenol research in the nutrition field.

（多）酚能改善营养状况吗？它们能帮助预防人类疾病吗？尽管该领域的大多数研究人员会在没有进行重大讨论的情况下对这两个问题做出肯定的回答，但（多）酚研究仍然被认为是营养科学的一小部分。尽管科学界、政策制定者甚至消费者都意识到其潜在的健康益处，但膳食指南中（多）酚的存在以及合理的营养策略仍然非常有限。然而，有足够的证据表明，它们可以成为改善个人营养状况的宝贵资产，甚至可以降低患某些重大慢性病的风险。然而，这些证据不足以在大联盟打球。(多)酚不是必需的，包含一个非常广泛的化学结构家族，呈现复杂的新陈代谢，并且广泛存在于植物性食品和饮料中。并非所有（多）酚都是相同的，它们无处不在，而它们在新陈代谢和与其消耗相关的生理反应方面容易出现高个体间变异率。对于这些植物化学物质作为促进健康的化合物来说，这些特性似乎是缺点。当前的营养范式主要涉及营养素，被认为是必不可少的并且能够影响生理过程的分子。虽然它们在新陈代谢和与其消费相关的生理反应方面容易出现高个体间的变异率。对于这些植物化学物质作为促进健康的化合物来说，这些特性似乎是缺点。当前的营养范式主要涉及营养素，被认为是必不可少的并且能够影响生理过程的分子。虽然它们在新陈代谢和与其消费相关的生理反应方面容易出现高个体间的变异率。对于这些植物化学物质作为促进健康的化合物来说，这些特性似乎是缺点。当前的营养范式主要涉及营养素，被认为是必不可少的并且能够影响生理过程的分子。

（多）酚是非营养物质，但它们也能够驱动生理反应。也许他们应该在实际的营养场景中发挥更重要的作用，在这种情况下，通过营养过剩来预防疾病是主要挑战。它们被认可为能够改善人类健康的食品生物活性物质需要现实、稳健和可靠的见解。本期特刊收集了一系列原创研究文章和评论，展示了（多）酚对人类营养的重要性。它们为研究前沿提供了宝贵的贡献，并可能有助于推动科学界建立一种新的范式，不仅包括营养素，还包括食物中存在的所有生物活性分子。

（多）酚对人类健康的影响是多效的，并且已经发表了与不同身体系统相关的有趣发现。心血管情况已在（多）酚文献中得到广泛评估，而生物节律对膳食（多）酚保护作用的影响尚未得到任何详细考虑。Torres-Fuentes 等人的评论。^{[ 1 ]}讨论了这一主题，讨论了昼夜节律和季节节律对（多）酚影响的贡献，并加深了通常不考虑的因素的重要性。米伦科维奇等人。^{[ 2 ]}评估了可可黄烷-3-醇对中年男性的营养基因组和营养基因组学影响。保持免疫内皮屏障功能的完整性可能是这些黄酮类化合物在血管健康中众所周知的保护作用背后的分子机制之一。非显着性结果也有助于更好地了解对心脏代谢风险的关键生物标志物有影响的化合物。从这个意义上说，Aboufarrag 等人。^{[ 3 ]}报告称，在一项针对高脂血症参与者的随机、安慰剂对照、交叉试验中，越橘和黑米中的花青素提取物不会影响脂蛋白谱、功能或血糖控制。威廉姆森的评论^{[ 4 ]}支持先前关于花青素对葡萄糖稳态的弱影响的结果，同时它提供了关于有多少膳食（多）酚可以抑制葡萄糖转运蛋白和调节葡萄糖摄取的完整和机械概述。非常有趣的读物。

肠道健康是（多）酚的重要研究课题。塔拉德里德等人。^{[ 5 ]}进行了一项探索性试验，评估适度饮用红酒对活动期溃疡性结肠炎患者临床状态和症状的影响。除了粪便微生物群，他们还研究了唾液微生物群，因为口腔生态失调也可能在这种肠道疾病中发挥作用。在 Caco-2 细胞单层中，Iglesias 等人。^{[ 6 ]}还讨论了多酚姜黄素在减轻肠道屏障炎症和氧化应激以及保持单层完整性方面的能力。鲁伯特等人。^{[ 7 ]}使用 3D HCT116 球体筛选了结直肠癌背景下的膳食（多）酚及其肠道微生物群相关代谢物。使用优化的高通量成像方法，一些苯基-γ-戊内酯和酚酸能够抑制球体聚集。Carecho 等人也使用了球体。^{[ 8 ]}证明两种酚类代谢物能够穿过血脑屏障对帕金森病人类 3D 细胞模型的神经保护作用。这进一步支持了（多）酚代谢物在脑（病理）生理学中的作用。在这方面，Cheng 等人。^{[ 9 ]}通过对随机对照试验和亚组分析的荟萃分析，为黄酮类化合物对人类认知的积极影响提供了证据。

肠道微生物群对（多）酚代谢的重要性以及这可能如何影响它们的健康影响也已得到解决。Koistinen 等人。^{[ 10 ]}确定了一种酚类分解代谢物的模式，这种模式由植物乳杆菌发酵黑麦和结肠发酵产生，能够协同调节细菌生长。加西亚-维拉尔巴等人。^{[ 11 ]}全面回顾了尿石素、鞣花单宁和鞣花酸衍生的结肠代谢物的代谢、相关肠道微生物群和生物活性。迪佩德等人。^{[ 12 ]}使用体外粪便发酵模型评估黄烷-3-醇结构对酚类分解代谢物产生的影响。提供了关于 12 种单体黄烷-3-醇和原花青素的分解代谢途径以及与生物活性分解代谢物产生相关的化学计量的见解。未来的研究还应包括关注（多）酚对肠道微生物群的影响和生物活性代谢物的产生。Peron 等人的研究。^{[ 13 ]}显示了老年人富含（多）酚的饮食如何能够增加血清吲哚 3-丙酸。

Kuhnert 和 Clifford 巧妙地为（多）苯酚分析领域的任何人（而不仅仅是初学者）撰写了两篇必读文章。^{[ 14 ]}一篇文章解决了质谱注释和（多）苯酚代谢物鉴定中的“从业者困境”，而其伴随的评论提请注意（多）苯酚的 LC-MS 表征和定量的缺陷，提出了避免它们的策略. ^{[ 15 ]}凯课题组的文章，^{[ 16 ]}提出了一个膳食暴露库，包括宿主和肠道微生物组代谢物，用于非靶向代谢组学数据集的峰识别/注释。这是一个很好的实际例子，进一步支持了对良好分析实践的需求，以更好地了解（多）酚在人体中的作用。

本期特刊中描述的这一前沿科学可能为未来现实、可靠和稳健的干预和分析方法铺平道路。我们感谢所有作者，其中大多数是好朋友，感谢他们的宝贵贡献。我们希望科学界能像我们一样喜欢阅读它们，让我们一起塑造营养领域（多）酚研究的未来。