Precision Nutrition for Gut Health: Development of a novel seaweed-containing, gut microbiota targeted nutraceutical

肠道中含有人体内代谢最活跃的微生物群落，为宿主提供了无数的好处。疾病、年龄以及饮食和生活方式因素的变化会扰乱这一复杂的生态系统，通常会导致胃肠道问题，从而影响整体健康。针对肠道微生物区系的饮食干预措施，如益生元和益生菌，是安全和成熟的改善胃肠道健康的方法，通过有利地改变肠道细菌的组成(例如增加有益微生物的水平，如双歧杆菌)并产生具有积极的局部和系统影响的微生物代谢物。海藻是天然生物活性的丰富来源，包括抗氧化剂、维生素、矿物质和必需的微量营养素，如碘。此外，它们还含有大量营养素，如蛋白质和多糖(这是纤维的良好来源)。由于这些底物可以被肠道微生物利用，海藻的益生菌潜力引起了人们越来越大的兴趣。一种利用海藻生物活性力量的新型营养食品的开发，与更成熟的针对肠道微生物区系的饮食干预措施(如益生菌和益生菌)相结合，提供了一个令人兴奋的机会，可以应用精确营养方法来开发支持肠道健康的优化食品。我们假设一种含有海藻的、以肠道微生物区系为靶标的营养食品将积极地改变人类肠道微生物区系的组成和活性，从而改善肠道健康。目标1)表征一系列商业相关海藻物种的营养成分，然后收集和保存来自阿伯里斯特威斯地区的材料，以产生混合物种的制剂，用于纳入新的营养食品。2)使用实验室人体肠道模型系统，评估候选营养成分对体外肠道微生物区系的影响。来自Obj.1的制剂将a)单独用作唯一的碳原料，b)与已建立的肠道微生物区系目标干预措施，如益生菌和益生菌一起使用，以及c)合并到食品中(如饮料、谷类食品)。肠道模型样品的分子表型分析将提供含有海藻的干预是否有利于改变肠道微生物组成和代谢活性的评估。3)基于目标2的结果，推动新开发的营养食品作为食品，包括规模化生产，用于体内；4.4)通过在100名健康志愿者中进行为期8周的随机、非安慰剂对照、4臂平行的饮食干预试验(海藻、益生菌、益生元及联合)，评估营养食品在体内的影响。这项研究数字是基于我们之前的益生菌试验，并基于双歧杆菌(主要终点衡量标准)增加0.2log10的基础上。第二个终点将是肠道健康的临床测量(例如，来自自我报告的问卷数据的肠道习惯)，这些测量将与使用分子表型方法从基线和终点收集的粪便、血液和尿液样本获得的微生物和代谢特征进行回归。通过人类干预研究，我们将能够更好地确定一种新开发的营养食品在改变肠道微生物组成以调节功能，并最终改善肠道健康方面的有效性。这一新颖的建议结合了最先进的分析技术，对整个系统的饮食干预进行了全面评估。这可能会导致所使用的食品的健康声明，以及重大的科学、临床和社会利益。

The gut contains the most metabolically active microbial community in the human body, providing innumerable benefits to the host. Illness, age & changes in diet & lifestyle factors can disrupt this complex ecosystem, often causing gastrointestinal issues that can affect overall health. Dietary interventions targeting the gut microbiota such as prebiotics and probiotics are safe and well established approaches that improve gastrointestinal health, by favourably altering the composition of bacteria in the gut (e.g. increasing levels of beneficial microbes, such as bifidobacteria) and producing microbial metabolites which have positive local and systemic effects. Seaweeds are a rich source of natural bioactives including antioxidants, vitamins, minerals and essential micronutrients such as iodine. Furthermore, they contain macronutrients such as proteins and polysaccharides (which are a good source of fibre). Since these are substrates that can be utilised by gut microbes, the prebiotic potential of seaweed is of growing interest. The development of a novel nutraceutical harnessing the power of seaweed bioactives in conjunction with more established gut microbiota-targeted dietary interventions (such as prebiotics and probiotics), presents an exciting opportunity to apply a precision nutrition approach in developing an optimised food product to support gut health. We hypothesise that a seaweed-containing, gut microbiota-targeted nutraceutical, will positively alter the composition and activity of the human gut microbiota, resulting in improved gut health.Objectives1)To characterise the nutritional composition of a range of commercially-relevant seaweed species, then collect and preserve material from the Aberystwyth locality to generate mixed-species preparations for incorporation into the novel nutraceutical. 2)To assess the impact of candidate nutraceutical components on the gut microbiota in vitro, using a laboratory human gut model system. Preparations from Obj.1 will be used a) individually as sole carbon feedstocks, b) in conjunction with established gut microbiota targeted interventions such as probiotics and prebiotics, and c) incorporated into a food product (e.g. beverage, cereal bar). Molecular phenotyping of the gut model samples will provide assessment of whether the seaweed-containing intervention favourably alters gut microbial composition and metabolic activity.3)Based on Obj.2 outcomes, to progress the newly developed nutraceutical as a food product, including production at scale, for use in Obj.4.4)To assess the impact of the nutraceutical food product in vivo, by conducting a randomised, non-placebo controlled, 4-arm parallel (seaweed, probiotics, prebiotics, and combination), 8-week dietary intervention trial in 100 healthy volunteers, i.e. 25 on each arm. This study number is based upon our previous prebiotic trials and is powered based on a 0.2 log10 increase in bifidobacteria (primary endpoint measure). The secondary endpoint will be clinical measures of gut health (e.g. bowel habits from self-reported questionnaire data) which will be regressed against microbial and metabolic profiles acquired from stool, blood and urine samples collected at baseline and endline using molecular phenotyping approaches. These results will improve knowledge of microbes as well as biomarkers/molecular pathways involved in changes to gut health as a result of the nutraceutical intervention.Through the use of a human intervention study, we will be able to better determine effectiveness of a newly developed nutraceutical in altering gut microbial composition to modulate function, and ultimately, improve gut health. This novel proposal combines state-of-the-art analytical technologies to conduct a holistic assessment of dietary intervention on the entire system. This would lead to possible health claims for the food products used, as well as major scientific, clinical and societal interest.