Ma Yongkai, Ghiretti Lucia, Castellone Vincenzo, Mena Pedro, Rubert Josep
Food Quality and Design, Wageningen University & Research, Bornse Weilanden 9, Wageningen, 6708 WG, the Netherlands.
Human Nutrition Unit, Department of Food & Drug, University of Parma, Parma, Italy.
Free Radic Biol Med. 2025 Feb 1;227:582-592. doi: 10.1016/j.freeradbiomed.2024.12.034. Epub 2024 Dec 12.
Flavan-3-ols are the most found flavonoid compounds in the human diet. Polymeric and monomeric flavan-3-ols reach the colonic region intact, where the gut microbiota utilizes them as substrates. In this research work, we investigated the pattern of colonic metabolites associated with flavan-3-ols, conducting a comprehensive analysis that combined (un)targeted metabolomics and in vitro colonic models. Firstly, the proposed flavan-3-ol metabolic pathway was investigated in-depth using a static in vitro model inoculated with different fecal donors. An apple, (-)-epicatechin, and procyanidin C1 were employed as feeding conditions. Small phenolic acids, such as phenylpropanoic acid and 3,4-dihydroxybenzoic acid, were positively associated with the apple feeding condition. In contrast, 5-(3',4'-dihydroxyphenyl)-γ-valerolactone and other specific early intermediates like phenylvaleric acids were positively associated with (-)-epicatechin. Secondly, by employing a dynamic in vitro simulator model of the human digestion system (SHIME), we reconstructed the flavan-3-ol metabolic pathway regionally. In the proximal colon region, we localized catabolites, such as 5-(3',4'-dihydroxyphenyl)-γ-valerolactone, while in the distal region, we identified mainly small phenolics. Combining static and dynamic in vitro models, we observed differences in the release of flavan-3-ol catabolites, influenced by both the food structure (isolated compounds and a food matrix) and the colonic region. This study sheds light on the colonic catabolism of one of the main dietary (poly)phenols and localizes microbial metabolites.
黄烷-3-醇是人类饮食中最常见的类黄酮化合物。聚合态和单体态的黄烷-3-醇能够完整地到达结肠区域，肠道微生物群将其用作底物。在本研究中，我们通过结合（非）靶向代谢组学和体外结肠模型进行全面分析，研究了与黄烷-3-醇相关的结肠代谢物模式。首先，使用接种了不同粪便供体的静态体外模型深入研究了提出的黄烷-3-醇代谢途径。以苹果、（-）-表儿茶素和原花青素C1作为喂养条件。小酚酸，如苯丙酸和3,4-二羟基苯甲酸，与苹果喂养条件呈正相关。相比之下，5-（3'，4'-二羟基苯基）-γ-戊内酯和其他特定的早期中间体，如苯戊酸，与（-）-表儿茶素呈正相关。其次，通过使用人类消化系统的动态体外模拟模型（SHIME），我们在区域上重建了黄烷-3-醇代谢途径。在近端结肠区域，我们定位了分解代谢物，如5-（3'，4'-二羟基苯基）-γ-戊内酯，而在远端区域，我们主要鉴定出小酚类物质。结合静态和动态体外模型，我们观察到黄烷-3-醇分解代谢物的释放存在差异，这受到食物结构（分离的化合物和食物基质）和结肠区域的影响。这项研究揭示了主要膳食（多）酚类之一的结肠分解代谢，并定位了微生物代谢物。
