Protection from environmental enteric dysfunction and growth improvement in malnourished newborns by amplification of secretory IgA.
Publisher DOI
PubMed ID
38959887
Abstract
Environmental enteric dysfunction (EED) is a condition associated with malnutrition that can progress to malabsorption and villous atrophy. Severe EED results in linear growth stunting, slowed neurocognitive development, and unresponsiveness to oral vaccines. Prenatal exposure to malnutrition and breast feeding by malnourished mothers replicates EED. Pups are characterized by deprivation of secretory IgA (SIgA) and altered development of the gut immune system and microbiota. Extracellular ATP (eATP) released by microbiota limits T follicular helper (Tfh) cell activity and SIgA generation in Peyer's patches (PPs). Administration of a live biotherapeutic releasing the ATP-degrading enzyme apyrase to malnourished pups restores SIgA levels and ameliorates stunted growth. SIgA is instrumental in improving the growth and intestinal immune competence of mice while they are continuously fed a malnourished diet. The analysis of microbiota composition suggests that amplification of endogenous SIgA may exert a dominant function in correcting malnourishment dysbiosis and its consequences on host organisms, irrespective of the actual microbial ecology.
Date Issued
2024-07-16
Publication Type
Article
Subjects
T follicular helper cell breast milk environmental enteric dysfunction live biotherapeutic malnutrition microbiota mucosal immunity purinergic signaling secretory immunoglobulin
Language(s)
en
Author(s)
Perruzza, Lisa | |
Rezzonico Jost, Tanja | |
Raneri, Matteo | |
Gargari, Giorgio | |
Palatella, Martina | |
De Ponte Conti, Benedetta | |
Seehusen, Frauke | |
Heckmann, Julia | |
Viemann, Dorothee | |
Guglielmetti, Simone | |
Grassi, Fabio |
Journal
Cell reports. Medicine
Publisher
Elsevier
ISSN
2666-3791
Access(Rights)
open.access