Markers of Gut Inflammation May Predict Stunting in Infants

Mal-Ed field sites

Mal-Ed field sites

Biological markers – biomarkers – of gut inflammation found in stool may help identify young children at risk for stunted growth and target them for appropriate medical intervention.

In resource poor areas, like those in many regions of the developing world, living conditions can have a negative impact on the growth and development, and the overall health of children. These areas are often characterized by a lack of clean drinking water and poor sanitary conditions leading to an increased risk of intestinal infections and diarrheal disease, as well as other infectious diseases. Children in these areas are particularly at risk during the first two to three years of life when so much of their development (both physical and mental) occurs. When exposure to these conditions is combined with an insufficient diet, either in quantity, quality, or diversity, infants often experience less than optimal growth and development. Chronic undernutrition is not only due to not having enough to eat (caloric content); it is often due to the lack of adequate amounts of needed vitamins, minerals and other micronutrients that are provided by a diverse and balanced diet.

Undernutrition can result in inhibited growth in length (stunted) and/or weight (underweight) when compared to optimal growth as defined by the World Health Organization. In addition to inadequate diet, undernutrition may result in a limited ability to absorb important nutrients through the wall of the intestine. Limited absorption of nutrients may be caused by chronic inflammation of the gut due to repeated and prolonged exposure to enteric infections – viruses, bacteria, parasites – that may damage the intestine and inhibit normal nutrient absorption. Dr. Margaret Kosek of the Johns Hopkins Bloomberg School of Public Health and her colleagues in the MAL-ED Network hypothesized “…that intestinal inflammation, likely resulting from frequent enteric infections, is a prominent contributor to growth failure in infancy.”

The study was designed to determine whether increased gut inflammation at a specific point in time can be used to predict future growth failure. The ability to predict a potentially severe decrease in the rate of growth of a child might enable clinicians to intervene before irreparable damage is done. Linear growth failure (decreased change in height over a defined period of time) was chosen as an outcome growth measure because it is a better marker of a physiologic insult than changes in weight and may be a better predictor of permanent loss of human potential.

Using non-diarrheal stool samples from infants enrolled in the MAL-ED birth cohort project, an eight-site project designed to evaluate the interactions of malnutrition and enteric infections and their effects on growth and cognitive development, the study determined the levels of three indicators of inflammation (biomarkers): alpha-1-antitrypsin (AAT), neopterin (NEO), and myeloperoxidase (MPO). AAT, a protein normally found in the blood stream, can move from blood vessels into stool when the wall of the gut is damaged. Increased production of NEO by immune system cells in the gut is an indicator of an active adaptive immune response associated with inflammation. Similarly, increased levels of MPO indicate increased innate immune response activity.

The research results indicated that elevated levels of AAT, NEO or MPO in the stool of infants were associated with poorer growth over the subsequent six months. Moreover, when a composite score of all three biomarkers combined was used an even greater association with growth shortfalls was observed. The relationship between the levels of these biomarkers and growth outcomes were similar across the diverse conditions found at the eight study sites.

Test kits used to determine the levels of these biomarkers in stool are commercially available, relatively easy to use and affordable. The MAL-ED Network investigators hope that these or other biomarkers of gut inflammation could be used by clinicians to identify children at risk of becoming stunted and who could be targeted for appropriate interventions aimed at reducing gut inflammation, malnutrition and growth shortfalls.

Read the open access full-text scientific article: Kosek M, Haque R, Lima A, Babji S, Shrestha S, Qureshi S, Amidou S, Mduma E, Lee G, Yori PP, Guerrant RL, Bhutta Z, Mason C, Kang G, Kabir M, Amour C, Bessong P, Turab A, Seidman J, Olortegui MP, Quetz J, Lang D, Gratz J, Miller M, and Gottlieb M for the MAL-ED Network. Fecal markers of intestinal inflammation and permeability associated with the subsequent acquisition of linear growth deficits in infants. Am. J. Trop. Med. Hyg., 88(2), 2013, pp.390-396.