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

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.

Beneficial Effect of a Multistrain Synbiotic Prodefen® Plus on the Systemic and Vascular Alterations Associated with Metabolic Syndrome in Rats: The Role of the Neuronal Nitric Oxide Synthase and Protein Kinase A

“…Alterations in these pathways have been reported in different MtS models, including increases, decreases and no modifications in their activities [53,[57][58][59]. Even though only few inconsistent results were reported regarding the effect of probiotics and synbiotics on those pathways [60][61][62][63][64][65][66], their role in the phosphorylation and subsequent activation of nNOS is well demonstrated [27,51,67,68]. We found that the inhibition of either PKC or PI3K with calfostin C or LY294002 respectively reduced EFS-induced NO release in a similar extent in the three experimental groups.…”

A Galacto-Oligosaccharides Preparation Derived From Lactulose Protects Against Colorectal Cancer Development in an Animal Model

“…At the level of the Actinobacteria phylum, GOS-Lu cohort shows an increase in this bacteria, mainly due to more abundant populations of Bifidobacteriaceae family, and specially of Bifidobacterium genus, being associated to health benefits including protection against pro-inflammatory gut conditions but also against CRC ( Table 1 and Figure 9 ). This protection against CRC has been associated to NF-kB repression by these probiotic bacteria ( Roller et al, 2004a ; Kim et al, 2010 ; Celiberto et al, 2017 ; Paveljšek et al, 2018 ).…”

Distinctive probiotic features share common TLR2 ‐dependent signalling in intestinal epithelial cells

“…It is also difficult to compare the results of different studies where different protocols as well as different cell lines are used. Furthermore, cell lines only represent an approximation of the real biological state, so it is essential that these studies are supported by more complex models such as organoids or experiments on animal models, which were also the starting point of our study (Paveljšek et al, 2018).…”

“…Despite intensive research, the mechanisms behind cell signalling are not yet well understood. Our previous study on DSS‐induced colitic mouse model shows that a combination of two probiotic strains helped in the regeneration of the intestinal epithelium during pathogenesis via pathways that are known downstream targets of TLR2 (Paveljšek et al, 2018). In the present study, we aimed to reveal the TLR2‐mediated signalling pathways that are probably responsible for the regulation of the intestinal epithelial barrier.…”