Regulation of the polymeric immunoglobulin receptor by different phyla of colonic bacteria

Abstract

The lower gastrointestinal tracts of mammals are exposed daily to hundreds of trillions of beneficial bacteria. Secretory IgA antibodies are transported into the intestinal lumen by the polymeric immunoglobulin receptor (pIgR), where they influence the composition of the intestinal microbiota, prevent bacterial invasion, and contribute to mucosal homeostasis. To compare the stimulatory effects of the 4 major bacterial phyla found in the human gut, mRNA levels for pIgR, the pro‐inflammatory factors TNF and IL‐8, and A20, a negative regulator of NF‐κB, were measured in the human colonic epithelial cell‐line HT‐29 following co‐culture with heat‐killed bacteria. Lactobacillus acidophilus (a Gram+ Firmicute) and Bacteroidetes thetaiotamicron (a Gram‐ Bacteriodete), representing the two most abundant phyla of gut bacteria, did not stimulate gene expression. By contrast, Escherichia coli strain Nissle (a Gram‐ Proteobacterium) and Bifidobacterium longum (a Gram+ Actinobacterium), representing less abundant phyla, dramatically induced gene expression. Levels of TNF, IL‐8 and A20 mRNA peaked at 3 h and were down‐regulated by 24 h, whereas pIgR expression peaked at 24 h, indicating the use of different regulatory pathways. These results suggest that the composition of the colonic microbiota may alter the expression of pro‐ and anti‐inflammatory genes and influence mucosal homeostasis. Supported by the CCFA.