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 (2024). Protection from environmental enteric dysfunction and growth improvement in malnourished newborns by amplification of secretory IgA. (In Press). Cell reports. Medicine, p. 101639. Elsevier 10.1016/j.xcrm.2024.101639
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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.
Item Type: |
Journal Article (Original Article) |
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Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
ISSN: |
2666-3791 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
08 Jul 2024 15:26 |
Last Modified: |
09 Jul 2024 00:16 |
Publisher DOI: |
10.1016/j.xcrm.2024.101639 |
PubMed ID: |
38959887 |
Uncontrolled Keywords: |
T follicular helper cell breast milk environmental enteric dysfunction live biotherapeutic malnutrition microbiota mucosal immunity purinergic signaling secretory immunoglobulin |
BORIS DOI: |
10.48350/198493 |
URI: |
https://boris.unibe.ch/id/eprint/198493 |
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