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

点击翻译按钮获取中文摘要

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.