<i>Akkermansia muciniphila</i>'s <i>nifJ</i> gene enhances colostrum sIgA synthesis by branched-chain amino acid degradation to branched short-chain fatty acids.

Abstract

Colostrum secretory immunoglobulin A (sIgA) confers the first immune defense line for neonates to adapt to the external environment, while gut microbes have received attention for their high reactivity with sIgA. Here, we report that high levels of sIgA in sow colostrum are associated with the enrichment of Akkermansia muciniphila and branched-chain amino acid (BCAA) metabolism in the intestine. Mechanistically, we demonstrate through mice models that A. muciniphila-derived nifJ mediates BCAA degradation to branched short-chain fatty acids, which further enhance transforming growth factor-β (TGF-β) and C-C motif chemokine ligand 28 (CCL28) expression in mammary tissues through the G protein-coupled receptor pathway, ultimately increasing sIgA content in colostrum. These findings establish a mechanistic link between the maternal gut microbiota and offspring immune development, highlighting the specific functional localization of the nifJ gene of A. muciniphila.