Interplay Between Cruciferous Vegetables and the Gut Microbiome: A Multi-Omic Approach

Cruciferous vegetable consumption has been associated with a decreased risk of multiple types of cancers, thus presenting a cost-effective, non-pharmacological approach to cancer prevention through dietary intervention. Broccoli sprouts and Brussels sprouts are among the leading cruciferous vegetables under study and contain some similar and some distinct phytochemicals which can activate different, but complementary, mechanisms to promote health. While the cancer-preventative effects of cruciferous vegetables are typically attributed to glucosinolates and their metabolic products, isothiocyanates and indoles, other components of cruciferous vegetables could play a synergistic role in conferring cancer-protective and health promoting effects. Additionally, metabolism of phytochemicals from cruciferous vegetables by the gut microbiome could further lead to the production, inactivation, or clearance of bioactive dietary components. The gut microbiome is essential to the production of bioactive compounds from various food sources. For example, with soy isoflavones and pomegranate urolithins, the presence or absence of specific microbial taxa directly dictates which metabolites are produced. A similar paradigm could be extended to cruciferous vegetables in which the gut microbiome may play an important role in driving inter-individual metabolism of glucosinolates and isothiocyanates.Compounds from cruciferous vegetables are also known to alter microbiome composition and metabolism, suggesting a complex interplay between the microbiome and diet. Additionally, the microbes responsible for metabolism of glucosinolates, and other cruciferous vegetable phytochemicals, are still unclear, representing a major gap in knowledge. Many studies have been conducted in vivo, in human and rodent models, to examine the impact of cruciferous vegetable consumption on the gut microbiome, however, these analyses are typically strictly taxonomical and do not examine specific microbe-metabolite relationships. We recently reported (Bouranis et. al, Nutrients 2021) that the gut microbiome composition can influence production of glucosinolate-derived nitriles from cruciferous vegetables, showing that the presence or absence of specific microbes can influence the abundance of a single metabolite. Thus, we sought to take an untargeted approach to investigate other phytochemicals from cruciferous vegetables which the gut microbiome could play a role in generating. To investigate plant- and microbe-derived metabolites of cruciferous vegetable digestion and capture information about the microbiome, we utilized an ex vivo fecal incubation system. Our goals were to 1) understand the impact of cruciferous vegetables on the gut microbiome, 2) describe changes to the digestive metabolome following cruciferous vegetable consumption and 3) identify relationships between specific members of the gut microbiome and specific metabolites.

十字花科蔬菜的摄入与多种癌症风险降低密切相关，因此为通过膳食干预实现癌症预防提供了一种经济高效、非药物的可行途径。西兰花芽苗与抱子甘蓝是当前研究中的主流十字花科蔬菜，二者含有部分相似、部分独特的植物化学物（phytochemicals），可通过不同但互补的机制促进机体健康。尽管十字花科蔬菜的防癌功效通常被归因于硫代葡萄糖苷（glucosinolates）及其代谢产物异硫氰酸酯（isothiocyanates）与吲哚类化合物（indoles），但十字花科蔬菜的其他成分或许在发挥防癌与健康促进作用时具备协同效应。此外，肠道菌群（gut microbiome）对十字花科蔬菜中植物化学物的代谢过程，可进一步促成具有生物活性的膳食成分的生成、失活或清除。肠道菌群对于多种食物来源的生物活性化合物生成至关重要：以大豆异黄酮和石榴尿石素为例，特定微生物类群的存在与否直接决定了所生成的代谢物种类。类似的研究范式或可推广至十字花科蔬菜领域，其中肠道菌群可能在驱动个体间硫代葡萄糖苷与异硫氰酸酯代谢差异方面发挥关键作用。十字花科蔬菜来源的化合物还被证实可改变菌群组成与代谢模式，这表明肠道菌群与膳食之间存在复杂的相互作用。此外，负责代谢硫代葡萄糖苷及其他十字花科蔬菜植物化学物的微生物类群仍未明确，这是当前研究的一大知识空白。已有多项在人体和啮齿动物模型中开展的体内研究，探讨了十字花科蔬菜摄入对肠道菌群的影响，但这类分析通常仅局限于分类学层面，并未考察特定的微生物-代谢物关联。我们团队此前曾报道（Bouranis等，《Nutrients》2021），肠道菌群组成可影响十字花科蔬菜来源的硫代葡萄糖苷衍生腈类代谢物的生成，证实特定微生物的存在与否可影响单一代谢物的丰度。因此，本研究旨在采用非靶向分析方法（untargeted approach），探究肠道菌群可能参与生成的其他十字花科蔬菜植物化学物相关代谢物。为研究十字花科蔬菜消化过程中植物与微生物来源的代谢物，并获取菌群相关信息，本研究采用了体外粪便孵育体系（ex vivo fecal incubation system）。本研究的目标为：1）明确十字花科蔬菜对肠道菌群的影响；2）描述十字花科蔬菜摄入后消化代谢组（metabolome）的变化；3）识别肠道菌群特定成员与特定代谢物之间的关联。