Protection from environmental enteric dysfunction and growth improvement in malnourished newborns by amplification of secretory IgA

Environmental enteric dysfunction (EED) is a disease of the small intestine associated to malnutrition, which can progress to intestinal malabsorption and villous atrophy; these features have been related to mucosal inflammation and compromised intestinal barrier integrity. Severe EED results in linear growth stunting, slowed neurocognitive development and reduced responsiveness to oral vaccines. Here we describe an intergenerational model of malnutrition, which reproduces cardinal aspects of EED in the progeny of malnourished dams. Severe impoverishment of intestinal secretory IgA (SIgA) characterized malnourished mothers and offspring. We show that amplification of endogenous SIgA in newborns by administration of an apyrase-releasing Lactococcus lactis biotherapeutic (L. lactispNZ-Apyr) increased the percentage of SIgA-coated small intestinal bacteria to levels of well-nourished pups. SIgA was instrumental in improving pups growth and intestinal immune competence of animals while continuously fed a malnourished diet. These effects were accompanied by relatively modest modifications of small intestinal microbiota composition, suggesting amplification of endogenous SIgA may exert a dominant function in correcting malnourishment dysbiosis and its consequences on host organism irrespective of actual microbial ecology.