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

成年人的肠道中有大约100万亿种微生物，统称为“微生物区系”。肠道微生物区系主要由细菌组成，在维持我们的健康方面发挥着关键作用。微生物群帮助将食物加工成维持我们健康的有利能源，它还产生必要的维生素(如维生素K、叶酸、生物素)，防止肠道感染，并有助于我们免疫系统的发展。肠道内有1000多种不同类型的细菌，但不同个体的组成不同，可能会发生变化。重要的是，现在很明显，我们的微生物区系的变化与各种疾病有关，例如过敏、厌食症、自闭症、乳糜泻、克罗恩病/溃疡性结肠炎(IBD)、肥胖和糖尿病。然而，我们对微生物区系影响疾病状态的方式知之甚少，就像饮食影响我们肠道微生物区系的组成以影响疾病的方式一样。铁是几乎所有生命形式所需的一种次要但关键的饮食成分。人类缺铁是最常见的营养不良形式，导致缺铁性贫血(IDA)，仅在英国就有约240万成年人和230万儿童受到影响。IDA导致疲劳、注意力不集中、免疫力减弱以及在学校和工作中表现不佳--这是一个主要的经济和社会负担。IDA用口服补铁剂治疗，铁强化(如白面粉)可减少发病率。然而，补铁常常会引起不良的胃肠道副作用(恶心、腹痛、便秘、腹泻)。此外，越来越多的证据表明，膳食铁影响微生物区系的组成，补充铁会导致有益共生体水平的有害降低。这些变化是肠道健康的负面指标。事实上，饮食中额外的铁供应可以促进致病肠道细菌的生长，这反过来可能会引发虚弱的感染性腹泻。目前，尚不清楚铁如何增加这些种群和减少保护性的驻留微生物区系，也不清楚饮食铁如何影响肠道微生物区系。然而，这种由铁引起的微生物区系变化的一个主要组成部分很可能是由于我们肠道内不同类型的细菌对铁的反应方式的差异。不幸的是，膳食铁、肠道微生物区系与健康/疾病之间的关系仍然很少被探索，因此通过膳食铁制度积极操纵肠道微生物区系的潜力还不能被开发来促进我们的健康和抗击疾病。这个项目将使用我们的大肠(大多数肠道微生物区系居住的地方)的受控体外模型和人体试验来研究微生物区系的组成和代谢活动如何受到铁的影响，以及这对健康相关结果的影响。我们将探索不同的铁源以及增加或减少铁供应的饮食成分。益生元逆转不利的铁诱导的肠道微生物区系变化的能力也将被调查。此外，还将研究断奶期间铁对肠道微生物群的影响，因为这一关键时期涉及日粮铁含量和可获得性的急剧增加，以及肠道微生物群的重大变化。增加膳食铁的供应可能是断奶后形成类似成年动物的微生物区系的关键，这一可能性仍未被探索。因此，我们将阐明微生物区系与饮食和健康之间的关系，使我们能够向营养科学家、食品饮料行业、政府和公众等关键利益集团提供信息，以便将膳食铁对微生物区系状态的影响纳入改善健康的当前思维中。

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.