Dietary fibre optimisation in support of global health.

The human gut microbiota influences its host via multiple molecular pathways, including immune system interactions, the provision of nutrients and regulation of host physiology. Dietary fibre plays a crucial role in maintaining a healthy microbiota as its primary nutrient and energy source. Industrialisation has led to a massive decrease of habitual fibre intake in recent times, and fibre intakes across the world are below the national recommendations. This goes hand in hand with other factors in industrialised societies that may negatively affect the gut microbiota, such as medication and increased hygiene. Non-communicable diseases are on the rise in urbanised societies and the optimisation of dietary fibre intake can help to improve global health and prevent disease. Early life interventions shape the developing microbiota to counteract malnutrition, both in the context of industrialised nations with an overabundance of cheap, highly processed foods, as well as in Low- and Middle-Income Countries (LMICs). Adequate fibre intake should, however, be maintained across the life course to promote health. Here we will discuss the current state of dietary fibre research in the global context and consider different intervention approaches.

Improving gut health and growth in early life: a protocol for an individually randomised, two-arm, open-label, controlled trial of a synbiotic in infants in Kaffrine District, Senegal.

INTRODUCTION: Infants exposed to enteropathogens through poor sanitation and hygiene can develop a subclinical disorder of the gut called environmental enteric dysfunction (EED), characterised by abnormal intestinal histology and permeability. EED can contribute to stunting through reduced digestion and absorption of nutrients, increased susceptibility to infections, increased systemic inflammation and inhibition of growth hormones. EED can be apparent by age 12 weeks, highlighting the need for early intervention. Modulating the early life gut microbiota using synbiotics may improve resistance against colonisation of the gut by enteropathogens, reduce EED and improve linear growth. METHODS AND ANALYSIS: An individually randomised, two-arm, open-label, controlled trial will be conducted in Kaffrine District, Senegal. Infants will be recruited at birth and randomised to either receive a synbiotic containing two Bifidobacterium strains and one Lactobacillus strain, or no intervention, during the first 6 months of life. The impact of the intervention will be evaluated primarily by comparing length-for-age z-score at 12 months of age in infants in the intervention and control arms of the trial. Secondary outcome variables include biomarkers of intestinal inflammation, intestinal integrity and permeability, gut microbiota profiles, presence of enteropathogens, systemic inflammation, growth hormones, epigenetic status and episodes of illness during follow-up to age 24 months. DISCUSSION: This trial will contribute to the evidence base on the use of a synbiotic to improve linear growth by preventing or ameliorating EED in a low-resource setting. TRIAL REGISTRATION NUMBER: PACTR202102689928613.

Epigenetic studies in children at risk of stunting and their parents in India, Indonesia and Senegal: a UKRI GCRF Action Against Stunting Hub protocol paper.

INTRODUCTION: In 2020, an estimated 150 million children under the age of 5 years were stunted. Stunting results from early-life adversity and it is associated with significant physical and cognitive deficit, lifelong socioeconomic disadvantage and reduced life expectancy. There is a need to understand the causes of stunting and its effects in order to develop strategies to avoid it and to mitigate the consequences once stunting has occurred. Epigenetics is an important mechanism through which early-life factors are thought to influence biological function, with long-term consequences. We describe a series of epigenetic studies designed to understand how early-life adversity results in stunting and to inform the development of practical tools such as predictive markers and therapeutic targets. This work is part of the UKRI GCRF Action Against Stunting Hub. METHODS AND ANALYSIS: The project-in India, Indonesia and Senegal-comprises an observational study of mothers, fathers, and offspring (n=500) spanning the first 1000 days of life, and an intervention study in each country. Epigenetic status (DNA methylation) is determined in saliva from babies collected within 1 month of birth and again at 18 months of age, and from mothers and fathers around the time of birth. Epigenome-wide analysis is carried out using the Illumina EPIC array, augmented by high-definition sequencing approaches. Statistical analysis is carried out at the level of candidate genes/regions, higher dimensional epigenetic states and epigenome-wide association. Data analysis focuses on the determinants of stunting, the effectiveness of interventions, population comparisons and the link between epigenetics and other thematic areas, which include anthropometry, microbiome, gut health, parasitology, cognition, nutrition, food hygiene and water sanitation, food systems and the home environment. ETHICS AND DISSEMINATION: This study has been approved by the relevant Ethics Committees in Indonesia, India and Senegal, and the UK. Research data will be published and posted in public repositories.

Assessment of the role of gut health in childhood stunting in a multisite, longitudinal study in India, Indonesia and Senegal: a UKRI GCRF Action Against Stunting Hub protocol.

INTRODUCTION: Childhood stunting has a complex aetiology, with poor gut health being an important contributor. This study will assess inter-relationships between maternal and infant gut health indices and infant linear growth. Inter-relationships between gut health indices, systemic inflammation and growth hormones in early childhood will also be assessed. METHODS AND ANALYSIS: A longitudinal observational study of cohorts of 600 newborns and their mothers in India, Indonesia and Senegal will be conducted. Women will be recruited during pregnancy and their children followed up to age 24 months. Stool, urine and blood samples will be collected from the women and children for assessments of helminthic and protozoal parasites, bacterial pathogens, faecal microbiota taxa, biomarkers of environmental enteric dysfunction, systemic inflammation and growth hormones. Child anthropometric measurements will be collected at birth and at ages 3, 6, 9, 12, 18 and 24 months. The gut health indices will be integrated with cohort data from other Action Against Stunting Hub (AASH) workstreams for interdisciplinary analyses of childhood stunting and the development of a new typology of stunting. DISCUSSION: This study will advance scientific understanding of the role of gut health in childhood stunting and will contribute to a broader knowledge of the complex aetiology of this condition as part of the interdisciplinary AASH research to reduce the global burden of childhood stunting. ETHICS AND DISSEMINATION: This study has been approved by the relevant Ethics Committees in Senegal, India, and Indonesia and LSHTM. The results will be submitted for publication in peer-reviewed journals.