Mycotoxin exposure, intestinal inflammation and childhood stunting in India

Childhood stunting is recognised as 'one of the most significant impediments to human development' by the World Health Assembly and its aim to reduce global stunting rates by 40% by 2025 is now deemed unachievable. When growth is impaired in children at an early age, later development of cognitive capacity is also impacted and children are thought not to be able to reach their full potential. The first 1000 days of a child's life are crucial to determining the development in later life. Hence it is imperative that the multiple factors contributing to childhood stunting are identified, their interrelation understood and their route cause treated.
Undernutrition is an obvious risk factor for childhood stunting, but simple nutritional interventions have failed to solve the problem. Multiple dietary and environmental risk factors are likely to contribute, and in this study we aim to unpick these complex links.
The environment a child grows up in regarding access to clean water and basic sanitation as well as access to nutritious and safe food are likely to contribute to the healthy functioning of the child's digestive tract which will facilitate the utilisation of foods for the growth and development of the child.
Hence the proposed project aims to follow children from birth up to two years of age and from two to five years of age and link multiple measures of child growth, health status and intestinal function with dietary intakes and exposure food contaminants. The study will be conducted in rural areas of southern India where stunting is prevalent.
This study will identify the main contributors to stunting in children and will provide the necessary information to guide future intervention programmes aimed at improving the lives of children in affected areas and hence addressing the WHO childhood development targets.

This study will explore the mechanistic link between dietary mycotoxin exposure and childhood stunting, including intestinal inflammation.
Mycotoxins are highly toxic fungal metabolites which frequently contaminate important food commodities such as cereals, millets and groundnuts. Aflatoxin, trichothecenes and fumonisins have all been shown to markedly affect intestinal function through limiting nutrient absorption, disrupting intestinal barrier function and subsequently increasing translocation of bacterial pathogens and luminal pro-inflammatory stressors in numerous animal and in vitro models (8). Especially in the immature intestine, the effect of multiple mycotoxins is of great concern, but robust evidence in humans linking multi-mycotoxin exposure with stunting is lacking.
In India, stunting is highly prevalent, representing one third of the global population of stunted children of pre-school age. We hypothesise that dietary mycotoxin exposure increases the risk of childhood stunting by disrupting the integrity of the intestinal epithelium hence impairing nutrient utilisation and increasing the risk of intestinal infections.
In two cohorts of 100 children (birth - weaning and post-weaning) growth and health status will be monitored and information on feeding practices will be collected. Food samples, breastmilk samples and urine samples (6 monthly) will be analysed for multiple mycotoxins and blood and stool samples (annually) will be analysed for inflammatory markers and microbiome composition. Multiple regression analysis will assess the effect of mycotoxin exposure and other relevant risk factors and confounders to evaluate the magnitude of their contribution to stunting.
This detailed analysis of multi-mycotoxin exposure in children will help unravelling the different risk factors contributing to stunting. The outcome of this study will inform future interventions to be more effective in tackling this intractable global development problem.

At the outset of this project the team from University of Aberdeen will visit Hyderabad and will together with co-investigators from the Indian National Institute of Nutrition host a workshop to gather important stakeholders from academia, industry and policy makers to discuss the issues of mycotoxin contamination in foods in India. During this networking event, the current project and its aims will be presented and discussed and feedback from stakeholder will inform the detailed planning of the project. This workshop will establish a network of local stakeholders which will be developed and used to communicate and disseminate the progress and outcomes of the research to a wide-ranging audience and bring the study's findings close the potential end-users working in areas of public health and infant health, food production industries and food safety regulators.
Capacity building is an important component of the proposed study and will involve an extended research visit of Indian colleagues to the UK to participate in activities regarding the systematic literature review and dietary modelling. Furthermore, lab-based training will be provided during the visit on mycotoxin biomarker analysis in human urine samples. This methodology will then be established at NIN to facilitate a sustainable research infrastructure which will be utilised in the main study and beyond.
Public engagement activities are managed through the University of Aberdeen's Public Engagement in Research Unit (PERU) and its Press Office. Through these channels we will communicate an initial project brief highlighting the research topic and project idea together with key aims, objectives and outcomes at the outset of the project. Subsequent progress updates will be prepared in conjunction with publication of scientific publications. Two of the main outcomes for the development phase of the project are the systematic review of existing literature (activity 1) and the dietary modelling of mycotoxin exposure, nutrition, stunting and inflammation (activity 2). The findings from both activities will be disseminated to the research community though publication in the scientific literature. Furthermore, a summary of the development phase of the project will be produced by the project team and distributed though communication channels available at UoA and NIN in the form of science briefs and/or blogs which will be distributed though social media outlets.