The relationship between dietary iron and the gut microbiota. Can dietary iron regime be exploited to improve health?

点击翻译按钮获取中文摘要

The adult human gut is home to ~100 trillion microbes collectively known as the 'microbiota'. The gut microbiota is largely composed of bacteria and plays a key role in maintaining our wellbeing. The microbiota assists in processing food into favourable energy sources that sustain our health, and it also generates essential vitamins (e.g. vitamin K, folate, biotin), protects against gut infections and contributes to the development of our immune system. Over 1000 different types of bacteria reside within the gut, but composition varies between individuals and is subject to change. Importantly, it is now clear that alterations in our microbiota are linked to various diseases, e.g. allergy, anorexia, autism, Coeliac's disease, Crohn's disease/Ulcerative Colitis (IBD), obesity and diabetes. However, the manner in which disease state is influenced by our microbiota is poorly understood, as is the way in which diet affects the composition of our gut microbiota to influence disease.Iron is a minor yet crucial dietary component required by virtually all lifeforms. Iron deficiency in humans is the most common form of malnutrition causing iron-deficiency anaemia (IDA) affecting ~2.4 million adults and ~2.3 million children in the UK alone. IDA causes fatigue, poor concentration, weakened immunity and poor performance at school and work - representing a major economic and societal burden. IDA is treated by oral iron supplements and incidence may be reduced by iron fortification (e.g. white flour). However, iron supplements often cause undesirable gastrointestinal side-effects (nausea, abdominal pain, constipation, diarrhoea). In addition, there is mounting evidence demonstrating that dietary iron influences composition of the microbiota, with iron supplementation causing deleterious reductions in levels of beneficial commensals. Such changes are negative indicators of gut health. Indeed, extra iron provision in the diet can promote growth of pathogenic enterobacteria which may in turn provoke debilitating infectious diarrhoea. Currently, it is not clear how iron enhances these populations and diminishes the protective resident microbiota, nor is it understood how dietary iron influences the gut microbiota in general. However, it is likely that a major component of such iron-induced alterations in the microbiota is due to differences in the way in which the distinct types of bacteria within our gut respond to iron. Unfortunately, the relationship between dietary iron, gut microbiota and health/disease remains little explored, and so the potential for positive manipulation of the gut microbiota through dietary-iron regime cannot yet be exploited to promote our health and combat disease.This project will employ controlled in vitro models of our large intestine (where most gut microbiota reside) and human trials to investigate how the composition and metabolic activity of the microbiota are influenced by iron, and the impact that this has on health-related outcomes. We will explore different iron sources as well as dietary components that enhance or decrease iron availability. The ability of prebiotics to reverse unfavourable iron-induced alterations in the gut microbiota will also be investigated. In addition, the impact of iron on the gut microbiota during weaning will be examined, as this crucial period involves a dramatic increase in dietary iron content and availability, along with major changes in the gut microbiome. Increases in dietary-iron provision may be key in the development of an 'adult'-like microbiota upon weaning, a possibility that remains unexplored. We will thus shed new light on the relationship between our microbiota, and diet & health, allowing us to inform key interest groups such as nutritional scientists, the food & drink industry, government and the general public so that the effects of dietary iron on the status of our microbiota can be incorporated into current thinking to improve health.