Location: Children's Nutrition Research Center
2016 Annual Report
Objectives
There is an ongoing need to enhance our understanding of the influences and role of various nutrients on fetal, postnatal, and childhood health, growth, and development as well as the etiology of obesity. A goal of this project is to provide evidence-based nutrient bioavailability data for the development of nutritional guidelines in children 6-24 months of age by: 1) using stable isotopes to assess the absorption of calcium, zinc, and magnesium over a range of usual dietary intakes in groups of children at 6-12, 12-18, and 18-24 months of age; 2) relate mineral absorption values to dietary mineral intake and body composition as determined by DXA; 3) evaluate mineral absorption and body composition in a group of preterm infants. We plan to increase understanding of how diet and age influence gut microbial population composition and promote health; we will: 4) determine effects of diet/age on gut microbial composition and relate these to gut barrier function and inflammation in children 7-18 years of age; 5) develop de novo method to assemble short sequence reads into contigs; apply method to assemble gut microbiome sequence reads; develop statistical method to cluster contigs and quantify abundance of these clusters; perform genetic association testing for haplotype-microbiome interactions that affect risk of childhood obesity; and 6) identify panel of human mRNAs indicative of environmental enteropathy (EE); evaluate as biomarker for EE in other populations; test whether micronutrient and/or fish oil supplements can reduce EE; explore microbiome of children with and without EE; correlate mRNA panel markers with child growth parameters. Additionally we will determine: 7) negative effect of obesity-induced inflammation and oxidative stress on women's fertility and if it can be reversed by weight loss and supplemental nutrients with antioxidant and anti-inflammatory properties; 8) if pre-pregnant lipid supply underlies the insulin resistance and increased susceptibility to gestational diabetes in obese women and if exercise and modified diet will decrease the prevalence of gestational diabetes; 9) whether children born to obese and/or gestational diabetic mothers have an altered macronutrient metabolism; 10) the relationship of vascular function to insulin resistance in youth; and relationship of monocyte function and serum inflammatory markers and vascular reactivity to insulin sensitivity; 11) the effect of hyperglycemia on endothelial function, monocyte function and inflammatory markers; and 12) individual variability, metabolic pathways, and genetic variants underlying differences in obligatory and adaptive components of energy expenditure and macronutrient utilization in non-obese and obese children.
Approach
A multi-discipline approach will be undertaken to improve our understanding of how foods support health, meet dietary requirements, and reduce disease risk such as cardiovascular disease and obesity. Our studies will utilize stable isotope techniques to provide accurate, practically applicable information that may be obtained from the study populations in a safe manner. Comparison will be made of intake and absorption of calcium and magnesium with total body bone mineral as determined by Dual Energy X-ray Absorptiometry. For magnesium and zinc, comparisons will be made of estimated retained minerals with expected tissue accretion rates in early childhood. We will also evaluate these values in a group of preterm infants who may have greater nutrient requirements due to the need to have catch-up growth. For other studies, obese and normal weight infertile women will be recruited, measured, and assigned a calorie-specific diet. Numerous biological measurements will be taken and correlations between body fat and other outcomes will be made. Additionally, we will conduct a cross-sectional study to evaluate endothelial dysfunction in obese youth with and without Type 2 diabetes compared with normal weight controls with the primary aim to explore the effect of insulin resistance vs. hyperglycemia on endothelial function. A cross-sectional study design will also take place comparing non-obese/obese adolescents wherein plasma samples will be collected and DNA will be sequenced and analyzed. Furthermore we will determine the effects of diet and age on gut microbial composition, ascertain the metagenomic profile of the gut microbes, and relate these to gut barrier function and inflammation in children 7-18 years of age; and develop a new de novo assembly method to assemble short sequence reads into long contiguous reads and apply this method to assemble gut microbiome sequence reads. Development of a statistical method to cluster contigs and quantify abundance of these clusters will occur, and we will perform genetic association testing for haplotype-microbiome interactions that affect the risk of childhood obesity. Researchers will identify a panel of human mRNAs in fecal samples indicative of environmental enteropathy, evaluate this panel as a biomarker for environmental enteropathy in other populations, test whether micronutrient and/or fish oil supplements can reduce environmental enteropathy.
Progress Report
Significant research progress was accomplished during the year. To review the progress, please refer to project 3092-51000-057-02S (Project #2), 3092-51000-057-03S (Project #3) and the new 3092-51000-057-04S (Project #4).
Accomplishments
1. Clinical trial to reduce gut inflammation. Rural African children often are stunted because of gut inflammation. Children's Nutrition Research Center researchers based in rural Malawi, Africa worked closely with 250 young children to see that they received either a daily combination of fish oil and vitamins or a placebo, a harmless substance with no active ingredients. The children had their gut health measured with a urine test while receiving the supplement and found that the fish oil and multivitamins did not improve gut health in this population. Having conducted this work using the most powerful clinical assessment tool, the randomized controlled clinical trial, the results constitute powerful evidence suggesting these simple dietary interventions are not enough to reduce gut inflammation in this population.
2. Treating severe childhood malnutrition: A global concern. Severe undernutrition is a major global health problem and it exists as two forms; a severe form that includes swelling and organ failure and a less severe form in which the body loses weight slowly without organ failure or swelling. The reason for the differences between the two forms is unclear; therefore treatment remains the same for both forms even though mortality and morbidity are higher with the more severe form. Researchers at the Children's Nutrition Research Center in Houston, Texas tested if the differences between the two groups are related to chemical modifications of DNA known (DNA methylation) and they observed that DNA methylation levels were significantly lower in children with the more severe form compared to those with the less severe form. Our results imply that the severity of undernutrition may be related to differences in DNA methylation and that specific nutrients in the diet could be a more effective treatment for the severe form of undernutrition
3. Identification of viruses in stool in children with gut inflammation. Researchers are interested in determining if children with gut inflammation have differences in the viruses in their gut compared to children that do not have inflammation. To do this, Children's Nutrition Research Center researchers based in Malawi, Africa worked to determine what viruses are present by a novel genetic sequencing method and the use of our custom software to interpret data. We have examined stool samples from children with gut inflammation and children without. We have detected numerous viruses in these samples including new viruses that have never before been known to exist.
4. A marker of early endothelial dysfunction in youth. Obese children have evidence of early changes in kidney function with hyperfiltration (increase in glomerular filtration rate) and increase in urine albumin excretion, indicators of early kidney abnormality and the causes of these changes are not clear. Researchers at the Children's Nutrition Research Center in Houston, Texas investigated whether increased urine albumin excretion (microalbuminuria) is related to insulin resistance and endothelial function in obese adolescents. We demonstrated that increased albumin excretion even though within the so-called "normal range" is related to endothelial function in children and therefore, endothelial dysfunction may mediate the link between insulin resistance in obesity and early microalbuminuria. We have shown that urinary albumin excretion is an easily obtainable measure, suitable for clinical studies aiming at assessment of cardiovascular disease risk in children and may constitute a biomarker for intervention studies that target changes in vascular function and cardiovascular disease risk.
5. Changes in the types of gut bacteria with age. A lack of knowledge exists regarding if there are changes in the types of gut bacteria with age and what relationship they may have to human disease. In a preliminary study, researchers at the Children's Nutrition Research Center in Houston, Texas surveyed the types of gut bacteria present in children 7-12 years of age and compared the types of bacteria present to those found in adults based upon data from the human (adult) microbiome project. Previous studies have suggested that by 3-4 years of age the gut bacteria in children are similar to those in adults however, investigating a larger number of children with more precise techniques, we found that the gut population of children in this age group is still undergoing development. Very importantly, when we examined the genetic potential of the gut bacteria, we found that children's gut bacterial communities were enriched in functions which may support ongoing development, while adult communities were enriched in functions associated with inflammation, obesity, and increased risk of adiposity. These observations suggest an opportunity to seek ways to alter the development of the gut bacterial population to help prevent adult onset diseases.
6. Food intolerances in healthy children. A lack of knowledge exists regarding why otherwise healthy children have food intolerances. Using our food questionnaire, researchers at the Children's Nutrition Research Center in Houston, Texas investigated whether healthy children perceive that they have intolerances to certain foods. We found that 62.5% of children 7-18 years of age identify, most commonly, with two foods to which they have an adverse reaction which led 41% of them to avoid certain foods. Moving forward, we plan to investigate whether the types of gut bacteria play a role in causing these intolerances given the importance of gut bacteria in helping to digest and process certain foods.
Review Publications
Yu, D., Gadkari, M., Zhou, Q., Yu, S., Gao, N., Guan, Y., Schady, D., Roshan, T.N., Chen, M., Laritsky, E., Ge, Z., Wang, H., Chen, R., Westwater, C., Bry, L., Waterland, R.A., Moriarty, C., Hwang, C., Swennes, A.G., Moore, S.R., Shen, L. 2015. Postnatal epigenetic regulation of intestinal stem cells requires DNA methylation and is guided by the microbiome. Genome Biology. 16:211.
Zhou, Q., Zhao, L., Guan, Y. 2016. Strong selection at MHC in Mexicans since admixture. PLoS Genetics. 2(2):e1005847.
Kao, C.C., Cope, J.L., Hsu, J.W., Dwarkanath, P., Karnes, J.M., Luna, R.A., Hollister, E.B., Thame, M.M., Kurpad, A.V., Jahoor, F. 2016. The microbiome, intestinal function, and arginine metabolism of healthy Indian women are different from those of American and Jamaican women. Journal of Nutrition. doi:10.3945/jn.115.227579.
Dwarkanath, P., Hsu, J.W., Tang, G.J., Anand, P., Thomas, T., Thomas, A., Sheela, C.N., Kurpad, A.V., Jahoor, F. 2016. Energy and protein supplementation does not affect protein and amino acid kinetics or pregnancy outcomes in underweight Indian women. Journal of Nutrition. 146(2):218-226.
Tan, H.C., Roberts, J., Catov, J., Krishnamurthy, R., Shypailo, R., Bacha, F. 2015. Mother's pre-pregnancy BMI is an important determinant of adverse cardiometabolic risk in childhood. Pediatric Diabetes. 16(6):419-426.
Bartz, S.K., Caldas, M.C., Tomsa, A., Krishnamurthy, R., Bacha, F. 2015. Urine albumin to creatinine ratio: A marker of early endothelial dysfunction in youth. Journal of Clinical Endocrinology and Metabolism. 100(9):3393-3399.
Silverstein, J., Cheng, P., Ruedy, K.J., Kollman, C., Beck, R.W., Klingensmith, G.J., Wood, J.R., Willi, S., Bacha, F., Lee, J., Cengiz, E., Redondo, M.J., Tamborlane, W.V. 2015. Depressive symptoms in youth with type 1 or type 2 diabetes: Results of the Pediatric Diabetes Consortium screening assessment of depression in diabetes study. Diabetes Care. 38(12):2341-2343.
Libman, I.M., Miller, K.M., Dimeglio, L.A., Bethin, K.E., Katz, M.L., Bacha, F. 2015. Effect of metformin added to insulin on glycemic control among overweight/obese adolescents with type 1 diabetes: A randomized clinical trial. Journal of the American Medical Association. 314(21):2241-2250.
Nambam, B., Silverstein, J., Cheng, P., Ruedy, K.J., Beck, R.W., Paul Wadwa, R., Klingensmith, G., Willi, S.M., Wood, J.R., Bacha, F., Thomas, I.H., Tamborlane, W.V. 2016. A cross-sectional view of the current state of treatment of youth with type 2 diabetes in the USA: Enrollment data from the Pediatric Diabetes Consortium type 2 diabetes registry. Pediatric Diabetes. doi:10.1111/pedi.12377.
Bacha, F., Gidding, S.S. 2016. Cardiac abnormalities in youth with obesity and type 2 diabetes. Current Diabetes Reports. 16(7):62.
Wood, J.R., Connor, C.G., Cheng, P., Ruedy, K.J., Tamborlane, W.V., Klingensmith, G., Schatz, D., Gregg, B., Cengiz, E., Willi, S., Bacha, F., Beck, R.W. 2015. Vitamin D status in youth with type 1 and type 2 diabetes enrolled in the Pediatric Diabetes Consortium (PDC) is not worse than in youth without diabetes. Pediatric Diabetes. doi:10.1111/pedi.12340.
Mohd Nor, N.S., Lee, S.J., Bacha, F., Tfayli, H., Arslanian, S. 2015. Triglyceride glucose index as a surrogate measure of insulin sensitivity in obese adolescents with normoglycemia, prediabetes, and type 2 diabetes mellitus: Comparison with the hyperinsulinemic–euglycemic clamp. Pediatric Diabetes. doi:10.1111/pedi.12303.
Bacha, F., Bartz, S.K. 2015. Insulin resistance, role of metformin and other noninsulin therapies in pediatric type 1 diabetes. Pediatric Diabetes. doi:10.1111/pedi.12337.
Michaliszyn, S.F., Lee, S.J., Bacha, F., Tfayli, H., Farchoukh, L., Mari, A., Ferrannini, E., Arslanian, S. 2017. Differences in beta-cell function and insulin secretion in Black vs. White obese adolescents: Do incretin hormones play a role? Pediatric Diabetes. 18(2):143-151.
Kruger, H.S., Butte, N.F. 2015. Nutrition in pregnancy and lactation. World Review of Nutrition and Dietetics. 111:64-70.
Butte, N.F., Puyau, M.R., Wilson, T.A., Liu, Y., Wong, W.W., Adolph, A.L., Zakeri, I.F. 2016. Role of physical activity and sleep duration in growth and body composition of preschool-aged children. Obesity. 24(6):1328-1335.
Romere, C., Duerrschmid, C., Bournat, J., Constable, P., Jain, M., Xia, F., Saha, P.K., Del Solar, M., Zhu, B., York, B., Sarkar, P., Rendon, D.A., Gaber, M.W., Lemaire, S.A., Coselli, J.S., Milewicz, D.M., Sutton, V.R., Butte, N.F., Moore, D.D., Chopra, A.R. 2016. Asprosin, a fasting-induced glucogenic protein hormone. Cell. 165:566-579.
Gilmore, L.A., Butte, N.F., Ravussin, E., Han, H., Burton, J.H., Redman, L.M. 2016. Energy intake and energy expenditure for determining excess weight gain in pregnant women. American Journal of Obstetrics and Gynecology. 127(5):884-892.
Pasch, L.A., Penilla, C., Tschann, J.M., Martinez, S.M., Deardorff, J., De Groat, C.L., Gregorich, S.E., Flores, E., Butte, N., Greenspan, L.C. 2016. Preferred child body size and parental underestimation of child weight in Mexican-American families. Maternal and Child Health Journal. doi:10.1007/s10995-016-1987-z.
Mou, Z., Hyde, T.M., Lipska, B.K., Martinowich, K., Wei, P., Ong, C., Hunter, L.A., Palaguachi, G.I., Morgun, E., Teng, R., Lai, C., Condarco, T.A., Demidowich, A.P., Krause, A.J., Marshall, L.J., Haack, K., Voruganti, V.S., Cole, S.A., Butte, N.F., Comuzzie, A.G., Nalls, M.A., Zonderman, A.B., Singleton, A.B., Evans, M.K., Martin, B., Maudsley, S., Tsao, J.W., Kleinman, J.E., Yanovski, J.A., Han, J.C. 2015. Human obesity associated with an intronic SNP in the brain- derived neurotrophic factor locus. Cell Reports. 13(6):1073-1080.
Williams, A.E., Czyzewski, D.I., Self, M.M., Shulman, R.J. 2015. Are child anxiety and somatization associated with pain in pain-related functional gastrointestinal disorders? Health Psychology. 20(4):369-379.
Chumpitazi, B.P., Shulman, R.J. 2016. Underlying molecular and cellular mechanisms in childhood irritable bowel syndrome. Molecular and Cellular Pediatrics. 3(1):11.
Butte, N.F. 2015. Energy requirements of infants, children and adolescents. In: Koletzko, B., editor. Nutrition Review of Nutrition and Dietetics - Pediatric Nutrition in Practice. Unionville, CT: S. Karger Publishers, Inc. 2nd Edition. 113:34-40. doi:10.1159/000360315.
Varni, J.W., Franciosi, J.P., Shulman, R.J., Saeed, S., Nurko, S., Neigut, D.A., Bendo, C.B., Patel, A.S., Self, M.M., Saps, M., Zacur, G.M., Denham, J., Dark, C.V., Pohl, J.F. 2015. PedsQL gastrointestinal symptoms scales and gastrointestinal worry scales in pediatric patients with inflammatory bowel disease in comparison with healthy controls. Inflammatory Bowel Diseases. (5)21:1115-1124.
Shulman, R.J., Jarrett, M.E., Cain, K.C., Broussard, E.K., Heitkemper, M.M. 2014. Associations among gut permeability, inflammatory markers, and symptoms in patients with irritable bowel syndrome. American Journal of Gastroenterology. 49(11):1467-1476.
Graham, M.H., Bush, J.A., Olvera, N., Puyau, M.R., Butte, N.F. 2014. Effectiveness of the modified progressive aerobic capacity endurance run test for assessing aerobic fitness in Hispanic children who are obese. The Journal of Strength and Conditioning Research. 28(10):2880-2887.
Varni, J.W., Nurko, S., Shulman, R.J., Self, M.M., Saps, M., Bendo, C.B., Dark, C.V., Pohl, J.F. 2015. Pediatric functional constipation gastrointestinal symptom profile compared with healthy controls. Journal of Pediatric Gastroenterology and Nutrition. 61(4):424-430.
Dubose, S.N., Hermann, J.M., Tamborlane, W.V., Beck, R.W., Dost, A., DiMeglio, L.A., Schwab K.O., Holl, R.W., Hofer, S.E., Maahs, D.M. 2015. Obesity in youth with type 1 diabetes in Germany, Austria, and the United States. Journal of Pediatrics. 167(3):627-632.
Hiremath, G., Byramji, D., Pacheco, A., Constantine, G., Davis, C., Shulman, R., Olive, A. 2015. Eosinophilic esophagitis in children and its relationship with parental allergies: Texas Children's Hospital experience. Digestive Disease and Science. 61(2):501-506.
Varni, J.W., Bendo, C.B., Nurko, S., Shulman, R.J., Self, M.M., Franciosi, J.P., Saps, M., Pohl, J.F. 2015. Health-related quality of life in pediatric patients with functional and organic gastrointestinal diseases. Journal of Pediatrics. 166:85-90.
Wong, G.K., Shulman, R.J., Chumpitazi, B.P. 2015. Gastric emptying scintigraphy results in children are affected by age, anthropometric factors, and study duration. Neurogastroenterology & Motility. 27(3):356-362.
Smith, H.E., Ryan, K.N., Stephenson, K.B., Westcott, C., Thakwalakwa, C., Maleta, K., Cheng, J.Y., Brenna, J.T., Shulman, R.J., Trehan, I., Manary, M.J. 2014. Multiple micronutrient supplementation transiently ameliorates environmental enteropathy in Malawian children aged 12-35 months in a randomized controlled clinical trial. Journal of Nutrition. 144:2059-2065. doi:10.3945/jn.114.201673.
Shypailo, R.J. 2016. Stability evaluation and correction of a pulsed neutron generator prompt gamma activation analysis system. Journal of Radioanalytical and Nuclear Chemistry. 307(3):1781-1786.
Varni, J.W., Bendo, C.B., Denham, J., Shulman, R.J., Self, M.M., Neigut, D.A., Nurko, S., Patel, A.S., Franciosi, J.P., Saps, M., Yeckes, A., Pohl, J.F., Shehzad, S. 2015. PedsQL gastrointestinal symptoms scales and gastrointestinal worry scales in pediatric patients with functional and organic gastrointestinal diseases in comparison to healthy controls. Quality of Life Research. 24:363-378.
Klingensmith, G.J., Pyle, L., Nadeau, K.J., Barbour, L.A., Goland, R.S., Willi, S.M., Linder, B., White, N.H., TODAY Study Group. 2016. Pregnancy outcomes in youth with type 2 diabetes: The TODAY Study experience. Diabetes Care. 39(1):122-129.
Lee, B., Eskandari, R., Jones, K., Reddy, K.R., Quezada-Calvillo, R., Nichols, B.L., Rose, D.R., Hamaker, B.R., Pinto, B. 2012. Modulation of starch digestion for slow glucose release through "toggling" of activities of mucosal "alpha"-glucosidases. Journal of Biological Chemistry. 287(38):31929-31938.
Hollister, E.B., Riehle, K., Luna, R.A., Weidler, E.M., Rubio-Gonzales, M., Mistretta, T., Raza, S., Doddapaneni, H.V., Metcalf, G.A., Muzny, D.M., Gibbs, R.A., Petrosino, J.F., Shulman, R.J., Versalovic, J. 2015. Structure and function of the healthy pre-adolescent pediatric gut microbiome. BMC Microbiome. 3:36.doi 10.1186/s40168-015-0101-x.
Davidovics, Z.H., Carter, B.A., Luna, R.A., Hollister, E.B., Shulman, R.J., Versalovic, J. 2015. The fecal microbiome in pediatric patients with short bowel syndrome. Journal of Parenteral and Enteral Nutrition. 20(10):1-8.
Wong, W.W., Strizich, G., Heo, M., et al. 2016. Relationship between body fat and BMI in a U.S. Hispanic population-based cohort study: Results from HCHS/SOL. Obesity. doi: 10.1002/oby.21495.
Farhat, A.E., Sharma, S., Abrams, S.H., Wong, W.W., Barlow, S.E. 2016. Kamp K’aana, a 2-week residential weight management summer camp, shows long-term improvement in body mass index z scores. Journal of Pediatric Gastroenterology and Nutrition. 62:491-494.
Zhang, F.F., Roberts, S.B., Must, A., Wong, W.W., Gilhooly, C.H., Kelly, M.J., Parsons, S.K., Saltzman, E. 2015. Assessing dietary intake in childhood cancer survivors: Food frequency questionnaire versus 24-hour diet recalls. Journal of Pediatric Gastroenterology and Nutrition. 61(4):499-502.
Wong, W.W., Clarke, L.L. 2015. Accuracy of delta 18O isotope ratio measurements on the same sample by continuous-flow isotope-ratio mass spectrometry. Rapid Communications in Mass Spectrometry. 29: 2252-2256.
Kearns, G.L., Chumpitazi, B.P., Abdel-Rahman, S.M., Garg, U., Shulman, R.J. 2015. Systemic exposure to menthol following administration of peppermint oil to paediatric patients. BMJ Open. 5(8):e008375.
Czyzewski, D.I., Self, M.M., Williams, A.E., Weidler, E.M., Blatz, A.M., Shulman, R.J. 2016. Maintenance of pain in children with functional abdominal pain. Journal of Pediatric Gastroenterology and Nutrition. 62(3):393-398.
Self, M.M., Williams, A.E., Czyzewski, D.I., Weidler, E.M., Shulman, R.J. 2015. Agreement between prospective diary data and retrospective questionnaire report of abdominal pain and stooling symptoms in children with irritable bowel syndrome. Neurogastroenterology & Motility. 27(8):1110-1119.
Chumpoitazi, B.P., Self, M.M., Czyzewski, D.I., Cejka, S., Swank, P.R., Shulman, R.J. 2016. Bristol Stool Form Scale reliability and agreement decreases when determining Rome III stool form designations. Neurogastroenterology & Motility. 28(3):443-448.
Hsu, J.W., Thame, M.M., Gibson, R., Baker, T.M., Tang, G.J., Chacko, S.K., Jackson, A.A., Jahoor, F. 2016. Unlike pregnant adult women, pregnant adolescent girls cannot maintain glycine flux during late pregnancy because of decreased synthesis from serine. British Journal of Nutrition. 115(5):759-763.
Stobaugh, H.C., Ryan, K.N., Kennedy, J.A., Grise, J.B., Crocker, A.H., Thakwalakwa, C., Litkowski, P.E., Maleta, K.M., Manary, M.J., Trehan, I. 2016. Including whey protein and whey permeate in ready-to-use supplementary food improves recovery rates in children with moderate acute malnutrition: A randomized, double-blind clinical trial. American Journal of Clinical Nutrition. 103(3):926-933.
Benzoni, N., Korpe, P., Thakwalakwa, C., Maleta, K., Stephenson, K., Manary, M., Manary, M. 2015. Plasma endotoxin core antibody concentration and linear growth are unrelated in rural Malawian children aged 2-5 years. BMC Research Notes. 8:258.
Ordiz, M.I., May, T.D., Mihindukulasuriya, K., Martin, J., Crowley, J., Tarr, P.I., Ryan, K., Mortimer, E., Gopalsamy, G., Maleta, K., Mitreva, M., Young, G., Manary, M.J. 2015. The effect of dietary resistant starch type 2 on the microbiota and markers of gut inflammation in rural Malawi children. BMC Microbiome. 3:37.
Trehan, I., Benzoni, N.S., Wang, A.Z., Bollinger, L.B., Ngoma, T.N., Chimimba, U.K., Stephenson, K.B., Aqapova, S.E., Maleta, K.M., Manary, M.J. 2015. Common beans and cowpeas as complementary foods to reduce environmental enteric dysfunction and stunting in Malawian children: Study protocol for two randomized controlled trials. Trials. 16:520.
Reyes, A., Blanton, L.V., Cao, S., Zhao, G., Manary, M.J., Trehan, I., Smith, M.I., Wang, D., Virgin, H.W., Rohwer, F., Gordon, J.I. 2015. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition. Proceedings of the National Academy of Sciences. 112(38):11941-11946.
