Protective effects of Bifidobacterium bifidum FL-228.1 on dextran sulfate sodium-induced intestinal damage in mice

Eur J Nutr. 2023 Apr;62(3):1267-1280. doi: 10.1007/s00394-022-03064-x. Epub 2022 Dec 15.

Abstract

Purpose: Numerous studies have found that probiotics benefit the intestinal barrier. However, the prophylactic effects of probiotics on the intestinal barrier, i.e., if probiotics exert protective effects in healthy individuals to defend them against harmful elements, have seldomly been reported. The present study aimed to investigate the possible mechanisms of potential strains with the function of preventing intestinal barrier damage.

Methods: This study investigated nine potential probiotic strains using in vitro and in vivo models on their intestinal barrier-protecting properties. Transcriptomic was then employed to decipher the underlying mechanisms of action of the strains.

Results: The results showed that the strains, to varying degrees, regulated the ratio of interleukin (IL)-10 and IL-12 in peripheral blood mononuclear cells (PBMCs), increased the transepithelial electrical resistance (TEER) values, and decreased Caco-2 cell monolayers permeability. Correspondingly, the strains showed different prophylactic efficacies in protecting mice from dextran sulfate sodium (DSS)-induced intestinal barrier damage. Remarkably, Bifidobacterium bifidum FL-228.1 (FL-228.1) showed the best prophylactic efficacies in protecting mice from DSS-induced intestinal barrier damage. Further research suggested that FL-228.1 exerted its prophylactic effects by enhancing mucin 2 (Muc2) production and Claudin (Cldn)-4 in the colon. Furthermore, the transcriptomic and protein-protein interactions (PPI) analyses indicated that the inhibition of NLRP3 and the activation of PPARγ and TLR2 could be involved in protecting the intestinal barrier by FL-228.1.

Conclusion: Bifidobacterium bifidum FL-228.1 may be developed as a promising probiotic for the prevention of intestinal barrier damage via PPARγ/NLRP3/ TLR2 pathways by enhancing Muc2 and Cldn-4.

Keywords: Intestinal barrier; Mucin2; Probiotics; Tight junction proteins; Transcriptomics.

MeSH terms

  • Animals
  • Bifidobacterium bifidum*
  • Caco-2 Cells
  • Colitis* / metabolism
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Intestinal Mucosa / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Probiotics* / pharmacology
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism

Substances

  • Dextran Sulfate
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • PPAR gamma
  • Toll-Like Receptor 2