Use of metagenomics to understand the genetic basis of malnutrition Tahmeed Ahmed, Rashidul Haque, Abul Mansur Shamsir Ahmed, William A Petri Jr, and Alejandro Cravioto Childhood malnutrition is not just due to lack of nutrients, it can also be caused by enteric infections leading to intestinal inflammation and malabsorption of nutrients. Human genetic polymorphisms can alter host genes that affect nutrient absorption and metabolism. Changes in intestinal microbial ecology and the microbiome (the collective genome of the intestinal microbiota) can also affect the harvest of nutrients from the diet. A substantial proportion of malnourished children fail to recover due to inappropriate treatment. However, there may be other causes for treatment failure, including changes in the microbiome and infection with an enteropathogen, and a genetic predisposition to malnutrition may exist. It is, therefore, logical to undertake the following: 1) investigate genetic predisposition to malnutrition, 2) determine the genetic markers and biomarkers that can help identify children at risk of malnutrition, and 3) look for new treatment modalities that can improve the clinical management of children with malnutrition. © 2009 International Life Sciences Institute INTRODUCTION Poor nutrition is linked to more than one-third of all child deaths worldwide. Nearly one-third of children in the developing world are malnourished. Malnutrition in the first 2 years of life leads to irreversible damage to cognitive functions and physical capacity, and it is trans- mitted across generations as malnourished mothers give birth to low-birthweight children. Management of mal- nutrition today is a failure; according to the World Bank, only in East Asia and Latin America has there been a reduction in malnutrition in the last decade. Malnutrition today is not primarily due to a calorie deficit. This can be seen in any urban slum in the world, where well- nourished and malnourished children with equal access to calories are found side-by-side. Malnutrition is the result of an inadequate response of the host and the host’s gut microbiome to caloric deficit. Thus, for the treatment of malnutrition to be effective and the response to feeding optimal, the contributions of the gut microbiome, the human genome, enteropathogenic infections, and intesti- nal inflammation need to be considered. MAGNITUDE OF CHILDHOOD MALNUTRITION The magnitude of childhood malnutrition is huge yet hardly recognized in the planning of public health pro- grams. Severe acute malnutrition (SAM), characterized either by severe wasting (weight-for-height less than -3 standard deviations) or the presence of bipedal edema or a mid-upper-arm circumference of less than 11 cm, may be quite obvious and easy to identify. In developing coun- tries, about 3.5% of 556 million children under the age of 5 years suffer from SAM. 1 Mild and moderate types of childhood malnutrition are even more prevalent, but their significance in childhood morbidity and mortality is less well recognized. Currently, 20% of children in the developing world who are under the age of 5 years are underweight, with a weight-for-age of less than -2 SD. A Affiliations: T Ahmed, R Haque, Shamsir A, and A Cravioto are with the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh. WA Petri Jr is with the with the Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA. Correspondence: T Ahmed, Nutrition Program, ICDDR, B, 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, Bangladesh. E-mail: tahmeed@icddrb.org, Phone: +88-02-9899206, Fax: +88-02-8823116. Key words: genetic markers, malnutrition, metagenomics doi:10.1111/j.1753-4887.2009.00241.x Nutrition Reviews® Vol. 67(Suppl. 2):S201–S206 S201