2. Academic Validation
  3. Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells

Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells

  • BMC Microbiol. 2020 Nov 23;20(1):357. doi: 10.1186/s12866-020-02023-y.
Amy M Ehrlich 1,  Alline R Pacheco 2 3,  Bethany M Henrick 1 2 3,  Diana Taft 2 3,  Gege Xu 4,  M Nazmul Huda 5 6,  Darya Mishchuk 3,  Michael L Goodson 1,  Carolyn Slupsky 3 7,  Daniela Barile 2 3,  Carlito B Lebrilla 4,  Charles B Stephensen 6 7,  David A Mills 2 3,  Helen E Raybould 8
Affiliations

Affiliations

  • 1 Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.
  • 2 Foods for Health Institute, University of California, Davis, CA, USA.
  • 3 Department of Food Science and Technology, University of CA, Davis, CA, USA.
  • 4 Department of Chemistry, University of California, Davis, CA, USA.
  • 5 Enteric and Respiratory Infections Unit, Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.
  • 6 US Department of Agriculture, Western Human Nutrition Research Center, Davis, CA, USA.
  • 7 Department of Nutrition, University of California, Davis, CA, USA.
  • 8 Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA. [email protected].
PMID: 33225894 DOI: 10.1186/s12866-020-02023-y
Abstract

Background: Bifidobacterium longum subsp. infantis (B. infantis) is a commensal bacterium that colonizes the gastrointestinal tract of breast-fed infants. B. infantis can efficiently utilize the abundant supply of oligosaccharides found in human milk (HMO) to help establish residence. We hypothesized that metabolites from B. infantis grown on HMO produce a beneficial effect on the host.

Results: In a previous study, we demonstrated that B. infantis routinely dominated the fecal microbiota of a breast fed Bangladeshi infant cohort (1). Characterization of the fecal metabolome of binned samples representing high and low B. infantis populations from this cohort revealed higher amounts of the tryptophan metabolite indole-3-lactic acid (ILA) in feces with high levels of B. infantis. Further in vitro analysis confirmed that B. infantis produced significantly greater quantities of the ILA when grown on HMO versus lactose, suggesting a growth substrate relationship to ILA production. The direct effects of ILA were assessed in a macrophage cell line and intestinal epithelial cell lines. ILA (1-10 mM) significantly attenuated lipopolysaccharide (LPS)-induced activation of NF-kB in macrophages. ILA significantly attenuated TNF-α- and LPS-induced increase in the pro-inflammatory cytokine IL-8 in intestinal epithelial cells. ILA increased mRNA expression of the aryl hydrogen receptor (AhR)-target gene CYP1A1 and nuclear factor erythroid 2-related factor 2 (Nrf2)-targeted genes glutathione reductase 2 (GPX2), superoxide dismutase 2 (SOD2), and NAD(P) H dehydrogenase (NQO1). Pretreatment with either the AhR antagonist or Nrf-2 antagonist inhibited the response of ILA on downstream effectors.

Conclusions: These findings suggest that ILA, a predominant metabolite from B. infantis grown on HMO and elevated in infant stool high in B. infantis, and protects gut epithelial cells in culture via activation of the AhR and Nrf2 pathway.

Keywords

Aryl-hydrocarbon receptor; Indole-3-lactic acid; Milk oligosaccharides; Nuclear factor erythroid 2–related factor 2.

Figures
Products