Abstract
BackgroundWHO guidelines recommend zinc supplementation as a key adjunct therapy for childhood diarrhea in developing countries, however zinc’s anti-diarrheal effects remain only partially understood. Recently, it has been recognized that low-grade inflammation may influence stunting. In this study, we examined whether oral zinc supplementation could improve weight, intestinal inflammation, and diarrhea in undernourished weanling rats.MethodsRats were undernourished using a northeastern Brazil regional diet (RBD) for two weeks, followed by oral gavage with a saturated lactose solution (30 g/kg) in the last 7 days to induce osmotic diarrhea. Animals were checked for diarrhea daily after lactose intake. Blood was drawn in order to measure serum zinc levels by atomic absorption spectroscopy. Rats were euthanized to harvest jejunal tissue for histology and cytokine profiles by ELISA. In a subset of animals, spleen samples were harvested under aseptic conditions to quantify bacterial translocation.ResultsOral zinc supplementation increased serum zinc levels following lactose-induced osmotic diarrhea. In undernourished rats, zinc improved weight gain following osmotic diarrhea and significantly reduced diarrheal scores by the third day of lactose intake (p < 0.05), with improved jejunum histology (p < 0.0001). Zinc supplementation diminished bacterial translocation only in lactose-challenged undernourished rats (p = 0.03) compared with the untreated challenged controls and reduced intestinal IL-1β and TNF-α cytokines to control levels.ConclusionAltogether our findings provide novel mechanisms of zinc action in the setting of diarrhea and undernutrition and support the use of zinc to prevent the vicious cycle of malnutrition and diarrhea.
Highlights
WHO guidelines recommend zinc supplementation as a key adjunct therapy for childhood diarrhea in developing countries, zinc’s anti-diarrheal effects remain only partially understood
We have addressed whether zinc supplementation could benefit weight gain, intestinal inflammation and gut-to-blood bacterial translocation in weanling rats challenged by undernutrition, with or without lactose-induced osmotic diarrhea
Oral saturated lactose (30 g/kg by gavage, from the 8th day of experiment) induced significant weight loss after the 10th day (p < 0.05) in undernourished rats coinciding with the onset of osmotic diarrhea, compared with the undernourished group without lactose
Summary
WHO guidelines recommend zinc supplementation as a key adjunct therapy for childhood diarrhea in developing countries, zinc’s anti-diarrheal effects remain only partially understood. The vicious cycle of childhood undernutrition and infection may impair the efficacy of oral vaccines against life-threatening enteric pathogens and amplify this loop of intestinal barrier breakdown, bacterial translocation, and inflammation leading to poor nutrient absorption [6,7] All of this could potentially increase the global DALY (disability adjusted life years) due to diarrheal diseases or enteric infections to a level not previously considered [8]. Any improvements in water sanitation, food security, and antimicrobials may lead to better mucosal immunity, adapted gut microbiome, and de Queiroz et al BMC Gastroenterology 2014, 14:136 http://www.biomedcentral.com/1471-230X/14/136 improved intestinal barrier function All these factors are key to reduce the long-term and devastating effects of this vicious cycle on children’s development, helping to achieve full human potential. It is a key co-factor for IGF-1, collagen, osteocalcin, and alkaline phosphatase syntheses [11]
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