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

肠道包含人体中代谢最活跃的微生物群落，为宿主提供无数益处。疾病、年龄、饮食和生活方式的改变会破坏这个复杂的生态系统，通常会导致影响整体健康的胃肠道问题。靶向肠道微生物群的饮食干预，如益生元和益生菌，是安全和完善的方法，通过有利地改变肠道中细菌的组成（例如增加有益微生物，如双歧杆菌的水平）和产生具有积极的局部和全身作用的微生物代谢物，改善胃肠道健康。海藻是天然生物活性物质的丰富来源，包括抗氧化剂，维生素，矿物质和必需微量营养素，如碘。此外，它们含有大量营养素，如蛋白质和多糖（这是纤维的良好来源）。由于这些都是可以被肠道微生物利用的底物，海藻的益生元潜力越来越受到关注。利用海藻生物活性物质的力量与更成熟的肠道微生物群靶向饮食干预（如益生元和益生菌）相结合的新型营养药物的开发，提供了一个令人兴奋的机会，可以应用精确的营养方法来开发优化的食品以支持肠道健康。我们假设，一种含有海藻的、以肠道微生物为目标的营养品，将积极地改变人类肠道微生物的组成和活性，从而改善肠道健康。目的1）鉴定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，以产生混合物种制剂，用于掺入新型营养品中。2）使用实验室人类肠道模型系统，评估候选营养成分对体外肠道微生物群的影响。目标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群靶向干预措施（如益生菌和益生元）联合使用，以及c）掺入食品（如饮料、谷物棒）中。肠道模型样本的分子表型分析将提供对含海藻干预是否有利地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，将新开发的营养食品作为食品进行开发，包括大规模生产，用于目标4.4）通过进行一项随机、非安慰剂对照、在100名健康志愿者中进行的4组平行（海藻、益生菌、益生元和组合）、8周饮食干预试验，即每组25名。该研究编号基于我们之前的益生元试验，并基于0.2 log 10增加的益生菌（主要终点指标）。次要终点将是肠道健康的临床指标（例如，来自自我报告的问卷调查数据的排便习惯），将使用分子表型分析方法对基线和终点时采集的粪便、血液和尿液样本中的微生物和代谢特征进行回归分析。这些结果将提高对微生物以及营养干预导致肠道健康变化的生物标志物/分子途径的认识。通过使用人类干预研究，我们将能够更好地确定新开发的营养药物在改变肠道微生物组成以调节功能方面的有效性，并最终改善肠道健康。这项新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全面评估。这将导致所使用的食品可能具有健康声称，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.