Lactobacillus fermentum L930BB and Bifidobacterium animalis subsp. animalis IM386 initiate signalling pathways involved in intestinal epithelial barrier protection

Benef Microbes. 2018 Apr 25;9(3):515-525. doi: 10.3920/BM2017.0107. Epub 2018 Apr 10.

Abstract

The manipulation of intestinal microbiota with beneficial microbes represents a promising alternative or adjunct therapy in gastrointestinal disorders and inflammation. The current study aims to clarify the signalling pathways and evaluate the possible beneficial effects of the combination of two strains. We used a dextran sulphate sodium (DSS)-induced mouse model of colitis. RNA extracted from the middle part of the colon tissue was used for examination of the global gene expression with Affymetrix microarrays. An enrichment analysis of the KEGG pathways was performed, and a subset of genes associated with intestinal epithelial barrier function was verified with qPCR. A clinical condition assessment of the differently treated mice revealed that the combination of these two bacterial strains was safe for use as a dietary supplement. All animals treated with DSS had affected colons and suffered weight loss. There were very small differences between the diseased groups, although the depth of inflammation was lower when cyclosporine A or the strain mixture was used. We discovered that the prophylactic administration of the Lactobacillus fermentum L930BB (L930BB) and Bifidobacterium animalis subsp. animalis IM386 (IM386) strains led to an anti-apoptotic pathway through phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt and to the activation of pathways involved in the regulation of actin cytoskeleton via protein kinase C and GTPases. Reorganisation of actin cytoskeleton and decreased apoptosis are both helpful in intestinal epithelial cell reconstitution. We confirm important previous observations, showing that these pathways are downstream targets of Toll-like receptor 2 and fibroblast growth factor initiated signalling. Taken together, these results suggest that the combination of L930BB and IM386 could aid in the regeneration of the intestinal epithelium during pathogenesis via pattern recognition receptors and the stimulation of growth factor synthesis.

Keywords: dextran sulphate sodium; gastrointestinal disorders; inflammation; microarray.

MeSH terms

  • Animals
  • Bifidobacterium animalis / growth & development*
  • Body Weight
  • Colitis / chemically induced
  • Colitis / prevention & control
  • Colitis / therapy*
  • Colon / pathology
  • Dextran Sulfate / administration & dosage
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Gene Expression Profiling
  • Intestinal Mucosa / microbiology*
  • Intestinal Mucosa / physiology*
  • Limosilactobacillus fermentum / growth & development*
  • Mice
  • Microarray Analysis
  • Probiotics / administration & dosage*
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction*
  • Treatment Outcome

Substances

  • Dextran Sulfate