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

ABSTRACT: The underlying mechanisms of probiotics and postbiotics are not well understood, but it is known that both affect the adaptive and innate immune responses. In addition, there is a growing concept that some probiotic strains have common core mechanisms that provide certain health benefits. Here, we aimed to elucidate the signalization of the probiotic bacterial strains Lactobacillus paragasseri K7, Limosilactobacillus fermentum L930BB, Bifidobacterium animalis subsp. animalis IM386 and Lactiplantibacillus plantarum WCFS1. We showed in in vitro experiments that the tested probiotics exhibit common TLR2- and TLR10-dependent downstream signalling cascades involving inhibition of NF-?B signal transduction. Under inflammatory conditions, the probiotics activated phosphatidylinositol 3-kinase (PI3K)/Akt anti-apoptotic pathways and protein kinase C (PKC)-dependent pathways, which led to regulation of the actin cytoskeleton and tight junctions. These pathways contribute to the regeneration of the intestinal epithelium and modulation of the mucosal immune system, which, together with the inhibition of canonical TLR signalling, promote general immune tolerance. With this study we identified shared probiotic mechanisms and were the first to pinpoint the role of anti-inflammatory probiotic signalling through TLR10.

SUBMITTER: Paveljsek D

PROVIDER: S-EPMC7757178 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Paveljšek Diana D Ivičak-Kocjan Karolina K Treven Primož P Benčina Mojca M Jerala Roman R Rogelj Irena I

Cellular microbiology 20201001 1

The underlying mechanisms of probiotics and postbiotics are not well understood, but it is known that both affect the adaptive and innate immune responses. In addition, there is a growing concept that some probiotic strains have common core mechanisms that provide certain health benefits. Here, we aimed to elucidate the signalization of the probiotic bacterial strains Lactobacillus paragasseri K7, Limosilactobacillus fermentum L930BB, Bifidobacterium animalis subsp. animalis IM386 and Lactiplant ...[more]

PMID: 32945079

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Project description:Recent clinical trials indicate that probiotic administration in critical illness has potential to reduce nosocomial infections and improve clinical outcome. However, the mechanism(s) of probiotic-mediated protection against infection and sepsis remain elusive. The authors evaluated the effects of Lactobacillus rhamnosus GG (LGG) and Bifidobacterium longum (BL) on mortality, bacterial translocation, intestinal epithelial homeostasis, and inflammatory response in experimental model of septic peritonitis.Cecal ligation and puncture (n=14 per group) or sham laparotomy (n=8 per group) were performed on 3-week-old FVB/N weanling mice treated concomitantly with LGG, BL, or vehicle (orally gavaged). At 24 h, blood and colonic tissue were collected. In survival studies, mice were given probiotics every 24 h for 7 days (LGG, n=14; BL, n=10; or vehicle, n=13; shams, n=3 per group).Probiotics significantly improved mortality after sepsis (92 vs. 57% mortality for LGG and 92 vs. 50% mortality for BL; P=0.003). Bacteremia was markedly reduced in septic mice treated with either probiotic compared with vehicle treatment (4.39±0.56 vs. 1.07±1.54; P=0.0001 for LGG; vs. 2.70±1.89; P=0.016 for BL; data are expressed as mean±SD). Sepsis in untreated mice increased colonic apoptosis and reduced colonic proliferation. Probiotics significantly reduced markers of colonic apoptosis and returned colonic proliferation to sham levels. Probiotics led to significant reductions in systemic and colonic inflammatory cytokine expression versus septic animals. Our data suggest that involvement of the protein kinase B pathway (via AKT) and down-regulation of Toll-like receptor 2/Toll-like receptor 4 via MyD88 in the colon may play mechanistic roles in the observed probiotic benefits.Our data demonstrate that probiotic administration at initiation of sepsis can improve survival in pediatric experimental sepsis. The mechanism of this protection involves prevention of systemic bacteremia, perhaps via improved intestinal epithelial homeostasis, and attenuation of the local and systemic inflammatory responses.

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

Publications

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

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