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Research Project: Intestinal Microbiome and Childhood Feeding

Location: Children's Nutrition Research Center

2020 Annual Report

Objective 1: Compare the effects of inulin and fructo-oligosaccharides against a maltodextrin placebo in obese children, using a double-blind randomized controlled trial, to study weight loss, fecal microbiota and their functions. Objective 2: Among children from low-to-middle income countries with severe acute malnutrition (SAM) to: a) longitudinally characterize epigenomic, and metabolomic responses to SAM treatment; b) assess amino acid content of hair samples taken before, during, and after therapy to identify biochemical markers of nutritional status and therapeutic response, and; c) investigate the role of a newly identified hormone – Asprosin – in the recovery of satiety during SAM refeeding therapy by integrating serial measurements in plasma with clinical nutritional data on caloric intake and weight recovery. Objective 3: Conduct a clinical trial adding black-eyed peas to diets of young children at risk for stunting. Determine efficacy in reducing stunting and analyze fecal sample to understand potential mechanisms by which the food supplement ameliorates stunting. Assess dietary compliance in a novel, quantitative manner using a urinary biomarker for black eyed peas. Currently quercetin and ferulic acid are candidates for this biomarker.

A number of pressing nutritional issues face the US and other nations. Over 20% of children throughout the world are obese with even more children overweight; both associated with diabetes and heart disease. Given the importance of the gut bacteria in our general health and weight control, we will test via various sample analyses a dietary supplement (prebiotic) that selectively enhances the growth and activity of bacteria associated with leanness. We anticipate that this prebiotic will reduce the risk of overweight and obesity in children. At the opposite end of the nutritional spectrum, severe acute malnutrition directly contributes to deaths of more than a million children under 5 yrs. old each year globally. There is a lack of molecular and metabolic biomarkers of existing nutritional therapy limiting the ability to appropriately and adequately assess the utility of dietary supplementation. We will perform serial measures of DNA methylation and tissue metabolites to identify suitable biomarkers of nutritional deficit and recovery. In addition, stunting affects about 23% of all children under 5 years of age globally. Most of these children are in Africa and south Asia and the consequences include lower economic productivity, decreased cognition and more diabetes and hypertension. Similar to obesity, the microbiome is implicated as a cause of stunting and new treatments are needed. We will determine using biomarker analysis if legume supplements can extend their benefits to children in West Africa.

Progress Report
For Objective 1, identifying sources for the treatments (inulin, fructo-oligosaccharides, maltodextrin) was obtained. The institutional review board (IRB) protocol was written and was submitted. Plans for recruitment using the Children's Nutrition Research Center database, advertisements on the Baylor College of Medicine website, and the Children's Nutrition Research Center website were developed. Advertisements were placed to accomplish the staffing increase needed to perform the study. Further progress was delayed by the COVID-19 pandemic and the additional restrictions caused by teleworking. In Objective 2A, the research study aimed at characterizing the change over time in DNA methylation and biochemical metabolites in response to the treatment of severe acute malnutrition (SAM), has been limited by personnel, location, and insufficient resources. The framework for undertaking this objective is in place; however, the originally identified center for this study is no longer available as a result of personnel changes. A new site in Uganda has been proposed and the director of that site has been approached; however, identifying additional trained personnel for sample-taking, and shipping has been challenging. Institutional review board approval cannot be sought until these uncertainties are resolved. For Objective 2B, we are conducting research looking at amino acid changes in SAM using hair samples taken at multiple time points which has progressed well since the start of the project. All components required for moving this objective forward are in place and available. IRB approval for the use of the samples has been sought and obtained. Baylor College of Medicine has agreed to accept the samples and perform biochemical testing for the amino acids desired. The subsequent COVID-19 pandemic shutdown, however, has delayed the submission of samples and their acceptance and testing in the core lab. This objective is expected to resume quickly once the respective labs are more fully operational. In Objective 2C, research is focusing on the role of Asprosin in SAM. The IRB approval for the use of metabolic samples has been obtained. Stored serum and urine samples from Jamaica have been identified, and logistics surrounding shipping and sample integrity have been agreed to by the accepting labs. The COVID-19 pandemic shutdown has delayed the submission, shipping and testing of samples, but this is expected to resume once the labs are fully operational. For Objective 3A, while the nature of the clinical trial with black-eyed pea supplements has been outlined and discussed with the key partners, we have not been able to move ahead with the feeding of children due to the uncertainty introduced by COVID-19. We will adjust activities to be COVID safe and to achieve the research objectives. The changing landscape with respect to The United States Agency for International Development (USAID) priorities and then the COVID-19 outbreak are the primary reasons for our inability to move ahead. In Objective 3B, substantial progress has been made with respect to finding a urinary test which will report the amount of black-eyed pea that has been consumed in the last 48 hours. The human studies testing protocol was written, implemented and completed. Each participant provided about 8 urine samples for a total of 320 samples. All that remains is for the samples to be analyzed and the pattern of urinary molecules that will serve as the measure of black-eyed pea consumption to be discovered.

1. The strength of the gut barrier differs between boys and girls. According to the latest Centers for Disease Control (CDC) report, the prevalence of obesity in children that are 12-19 years of age is 21%. Obesity is associated with a number of healthy complications, and in children, liver disease is prominent, particularly in boys versus girls. Recent studies show that gut bacteria can contribute to the development of liver disease related to obesity. However, the stronger the gut barrier, the less likely gut bacteria and their potentially toxic products can enter the bloodstream, contributing to liver disease. Researchers in Houston, Texas conducted studies that have shown that the gut barrier is weaker in boys than in girls. This may be part of the reason why boys are more at risk for liver disease related to obesity.