Bifidobacterium grown on human milk oligosaccharides produce tryptophan metabolite Indole‐3‐lactic acid that significantly decreases inflammation in intestinal cells in vitro

Abstract

Bifidobacterium longum subsp. infantis (B. infantis) is a commensal bacterium that colonizes the infant gastrointestinal tract. This bacterium can efficiently utilize the abundant supply of oligosaccharides found in human milk (HMO) to help establish residence and generate bioactive metabolites which may produce beneficial effects by acting directly on the host. We hypothesized that metabolites from Bifidobacterium grown on human milk oligosaccharides would reduce inflammation in the intestine. To test this we first needed to identify metabolite candidates by growing B. infantis on either lactose or HMO and analyzing the metabolites produced using NMR spectroscopy. These metabolites were then compared to those found in Bifidobacterium‐dominated infant fecal samples. Once specific metabolites were identified, we treated intestinal and macrophage cells grown in culture to test if they exhibited an anti‐inflammatory response during endotoxin challenge. Lastly, we sought to find which pathway might be activated. We found that B. infantis grown on HMO produced significantly greater quantities of the tryptophan metabolite indole‐3‐lactic acid (ILA). Significantly higher amounts of ILA were also found in fecal samples from a population of infants with high compared to low abundance of Bifidobacterium species. The direct effects of ILA were assessed in macrophage and intestinal epithelial cell lines. ILA (at concentrations from 1 to 10mM) significantly attenuated lipopolysaccharide (LPS)‐induced activation of NF‐kB in macrophages. Similarly, ILA significantly attenuated LPS‐induced increase in the pro‐inflammatory cytokine IL‐8. ILA acts through the aryl hydrogen receptor (AhR) in intestinal epithelial cells as shown through increased nuclear localization of the AhR as well as increased protein expression of the AhR targeted gene CYP1A1. Activation of the AhR has been shown to exert a multitude of beneficial effects on the host including promoting normal intestinal immune function. These findings suggest that ILA, a predominant metabolite from B. infantis, can protect the epithelium via activation of AhRThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.