Intestinal secretory IgA induction protects from enteropathy and stunting in malnutrition

A new study published by the Grassi laboratory and collaborators in “Cell Reports Medicine” demonstrates that releasing the inhibitory effect of adenosine-triphosphate (ATP) on secretory IgA production in the gut protects from enteropathy and restores growth in malnourished newborns.

Living in impoverished environments is the cause of stunting for almost 150 million children under 5 years of age. In these children, environmental enteric dysfunction (EED), a disease characterised by diarrhea and impaired nutrients absorption, is also variably associated to slowed neurocognitive development and reduced responsiveness to oral vaccines. A causal relationship has been established between the intestinal microbiota, EED and growth stunting. The Grassi lab has developed an experimental model of intergenerational malnutrition, which reproduces all the cardinal features of EED in newborns from malnourished mothers. This model was exploited to show that amplification of intestinal secretory IgA (SIgA) in malnourished pups by administration of an ATP-degrading Lactococcus lactis biotherapeutic, restores the conditioning of commensal microbes by SIgA coating, thereby improving the growth and intestinal fitness of malnourished animals. The study suggests SIgA amplification may exert a dominant function in correcting EED and its consequences on host organism.

The study was performed by Lisa Peruzza and other members of the Grassi lab in collaboration with the University of Milan, University of Zurich, University Hospital of Wurzburg, and supported by the Bill & Melinda Gates Foundation and the Swiss National Science Foundation.

Link to the article: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(24)00352-5