Bifidobacterium bifidum Ameliorates DSS-Induced Colitis in Mice by Regulating AHR/NRF2/NLRP3 Inflammasome Pathways through Indole-3-lactic Acid Production

J Agric Food Chem. 2023 Feb 1;71(4):1970-1981. doi: 10.1021/acs.jafc.2c06894. Epub 2023 Jan 12.

Abstract

In this study, the effectors and mechanisms of Bifidobacterium bifidum FL-276.1 and B. bifidum FL-228.1 in alleviating dextran sulfate sodium (DSS)-induced colitis were investigated. Both FL-276.1 and FL-228.1 significantly alleviated DSS-induced colitis, whether they were supplemented from the beginning of the experiment (whole course intervention) or after the DSS induction started (partial intervention). Aryl hydrocarbon receptor (AHR) and the nuclear factor erythroid 2-related factor 2 (NRF2) pathways were activated in mice colons, while the NLR family pyrin domain containing 3 (NLRP3) was downregulated under the whole course intervention modes. Indole-3-lactic acid, an AHR ligand produced by FL-276.1 and FL-228.1, could regulate the AHR/NRF2/NLRP3 pathway in Caco-2 monolayers, thus upregulating the tight junction proteins and protecting the integrity of the epithelial barrier. These results are conducive to promoting clinical trials and product development of probiotics for alleviating colitis.

Keywords: Bifidobacterium bifidum; aryl hydrocarbon receptor; indole-3-lactic acid; probiotics; ulcerative colitis.

MeSH terms

  • Animals
  • Bifidobacterium bifidum*
  • Caco-2 Cells
  • Colitis* / chemically induced
  • Colitis* / drug therapy
  • Colitis* / metabolism
  • Dextran Sulfate
  • Disease Models, Animal
  • Humans
  • Inflammasomes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism

Substances

  • Dextran Sulfate
  • indole-3-lactic acid
  • Inflammasomes
  • NF-E2-Related Factor 2
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Receptors, Aryl Hydrocarbon