Influence of prebiotics on human gut microbiota LPS and markers of metabolic syndrome.

肥胖正迅速成为21世纪最大的健康挑战。我们干预这种情况的能力的核心是清楚地了解饮食和肥胖之间的联系，以及工业提供能够降低风险的食品的能力。本项目将奠定肠道微生物区系与肥胖之间联系的科学合理性，并为肥胖者使用功能食品改善健康提供理性，旨在调节肠道细菌。肥胖和相关代谢紊乱的传统风险因素与饮食、遗传和运动有关。然而，有人认为，这些并不能完全解释近年来出现的爆炸性增长。这一点在2006年被赋予了额外的意义，当时第一批报告似乎表明，肥胖者和消瘦者的肠道细菌谱不同。这是假设，细菌图谱不同地影响食物中卡路里的提取速率，它们的一些代谢物可能会影响饱腹感。这仍然是一个有争议的领域(可能是传统的风险因素本身影响微生物区系)，但毫无疑问的是，肠道微生物区系在人类新陈代谢中发挥着重要作用。这是因为存在的数量巨大，而且它们不断地提供营养(主要是饮食)。如果肠道微生物区系的差异是肥胖相关疾病的一个因素，那么这就开启了通过使用具有选择性就地受精的饮食成分来改变这种情况的可能性。益生元是在人体肠道微生物区系中施加主要成分和新陈代谢变化的功能性食品成分。与益生菌一起，它们因其改善胃肠道健康的能力而吸引了人们的注意。新产品正在不断开发，主要任务是改善消化和健康。关于调节肠道菌群的研究主要针对肠道感染，包括与IBS和溃疡性结肠炎等慢性疾病的联系。鉴于最近肠道微生物区系与肥胖之间的联系，研究益生菌是否可以发挥调节作用是有意义的。在这个项目中，它们被选为益生菌，因为它们在改变肠道内的细菌种群方面更有效。我们在动物模型中的合作研究表明，内毒素是革兰氏菌的一种细胞壁成分，可以引起代谢性内毒素血症，这是人类糖尿病的特征。益生菌以革兰氏+Ve菌群(主要是双歧杆菌)为靶标。在小鼠身上的进一步研究表明，通过以双歧杆菌为代价抑制革兰氏杆菌，可以逆转内毒素的毒性效应。在这里，我们的目标是在有代谢综合征风险的人类身上重复这些实验。我们将使用一种经过验证的益生菌(Bimuno，一种低聚半乳糖GOS)，它最初是由我们的实验室开发的，现在已经可以商业使用，在人类喂养研究中针对双歧杆菌。在此之前，食品质量体验将应用于评估最合适的饮食递送载体，以保持成分的功能性和具有最佳的感官质量。一种安慰剂也将进行试验。其结果将是对改变肠道微生物区系的能力以及对代谢综合征有效标记物的伴随影响的体内评估。如果这项研究成功，它将导致一种饮食干预产品，通过改变微生物区系的影响，积极地影响与肥胖相关的风险。这将对21世纪的一个主要饮食问题产生很大影响，并与非常流行的功能食品方法相吻合。结果还将在一定程度上了解改变一个人的肠道微生物区系可预期的健康属性，并与益生菌和益生菌产业都有相关性。

Obesity is fast becoming the greatest health challenge of the 21st century. Central to our ability to intervene in this situation is a clear understanding of the link between diet and obesity and the ability of industry to deliver food products capable of reducing risk. This project will lay down the scientific rational linking the gut microbiota with obesity, and provide a rational for using functional foods in the obese for improved health, targeted towards modulating the gut bacteria. Traditional risk factors for obesity and associated metabolic disorders are dietary, genetic and exercise linked. However, there is the contention that these cannot fully explain the explosive increase seen in recent years. This was given added significance in 2006 when the first reports appeared suggeted that gut bacterial profiles in obese and lean persons differed. It was hypothesised that the bacterial profiles variably affected calory extraction rates from food and that some of their metabolites could influence satiety. This is still an area of some debate (and it may be that the traditional risk factors themselves affect microflora profiles), however what is not in question is that the gut microbiota has a major role to play in human metabolism. This is because of the huge numbers that are present and their constant supply of nutrients (principally diet). Should the gut microbiota differences be a factor in obese related conditions, then this opens up the possibily of altering the situation by using dietary ingredients that have a selective fernentation in situ. Prebiotics are functional foods ingredients that exert major composition and metabolic changes in the human gut microbiota. Together with probiotics, they are attracting much attention for their ability to improve gastrointestinal health. New products are constantly being developed, with the main remit being improved digestion and wellbeing. Research on modulating the gut flora has largely targeted gut infections including links into chronic disorders like IBS and ulcerative colitis. Given the recent link between gut microflora and obesity, it makes sense to research whether prebiotics can exert a modulatory role. In this project, these have been chosen over probiotics as they are more efficacious in exerting change in bacterial populations within the gut. Our collaborative research in an animal models has shown that LPS, a cell wall constituent of Gram -ve bacteria, can exert a metabolic endotoxaemia which is characteristic of diabetes in humans. Prebiotics target Gram+ve flora (principally bifidobacteria). Further studies in the murine showed that the toxic effects of LPS could be reversed by repressing Gram -ves at the expense of bifidobacteria. Here, we aim to replicate these experiments in humans at risk of metabolic syndrome. We will use a proven prebiotic (BiMuno, a type of galactooligosaccharide GOS), that was originally developed in our laboratories and is now commercially availble, to target bifidobacteria in a human feeding study. Prior to this, food quality experitise will be applied towards assessing the most appropriate dietary delivery vehicle that maintains functionality of the ingredient and has optimal sensory qualities. A placebo will also be trialled. The outcomes will be an in vivo assessment of the capacity to alter gut microbiota and concomitant effects upon validated markers of metabolic syndrome. If the research is successful it will lead towards a dietary intervention product that positively affects the risks associated with obesity in a manner that changes the microflora influence. This would have much impact upon a major 21st century dietary problem and tally that with an extremely topical functional food approach. The outcome would also partly inform on the health attributes that can be expected from altering a person's gut microbiota and has relevance for both the probiotic and prebiotic industries.