Abstract
The aim of this study was to investigate the effects of three Lactobacillus plantarum strains on in-vivo small intestinal barrier function and gut mucosal gene transcription in human subjects. The strains were selected for their differential effects on TLR signalling and tight junction protein rearrangement, which may lead to beneficial effects in a stressed human gut mucosa. Ten healthy volunteers participated in four different intervention periods: 7-day oral intake of either L. plantarum WCFS1, CIP104448, TIFN101 or placebo, proceeded by a 4 weeks wash-out period. Lactulose-rhamnose ratio (an indicator of small intestinal permeability) increased after intake of indomethacin, which was given as an artificial stressor of the gut mucosal barrier (mean ratio 0.06 ± 0.04 to 0.10 ± 0.06, p = 0.001), but was not significantly affected by the bacterial interventions. However, analysis in small intestinal biopsies, obtained by gastroduodenoscopy, demonstrated that particularly L. plantarum TIFN101 modulated gene transcription pathways related to cell-cell adhesion with high turnover of genes involved in tight- and adhesion junction protein synthesis and degradation (e.g. actinin alpha-4, metalloproteinase-2). These effects were less pronounced for L. plantarum WCFS1 and CIP104448. In conclusion, L. plantarum TIFN101 induced the most pronounced probiotic properties with specific gene transcriptional effects on repair processes in the compromised intestine of healthy subjects.
Highlights
No therapeutic agents have been developed that are able to successfully restore the intestinal mucosal barrier and thereby influence disease outcome[16]
To L. plantarum WCFS1, we have selected two more L. plantarum strains, i.e. CIP104448 (CIP48), and TIFN101, to be tested in the current study. They were selected based on research wherein these bacterial strains were shown to have differential effects in toll-like receptor (TLR) signalling in vitro and to affect both the innate and specific immune system both in vitro and in vivo[26,27,28]. It has recently been demonstrated in an in vitro model that TLR signalling is involved in regulation of the intestinal barrier function[29], it is unknown whether these three L. plantarum strains have positive effects on intestinal mucosal barrier in human subjects after ingestion, or through which mechanisms these live bacterial organisms may improve the human gut barrier function
We hypothesized that daily oral administration of L. plantarum WCFS1, CIP48, and TIFN101 over a 7-day period (i) will have positive effects on compromised intestinal barrier function in healthy human subjects, with regard to intestinal permeability, tight junction protein- and gene expression, and (ii) will induce alterations in the transcription of pathways involved in mucosal structure and cell function, as measured in duodenal biopsy material
Summary
No therapeutic agents have been developed that are able to successfully restore the intestinal mucosal barrier and thereby influence disease outcome[16]. They were selected based on research wherein these bacterial strains were shown to have differential effects in toll-like receptor (TLR) signalling in vitro and to affect both the innate and specific immune system both in vitro and in vivo[26,27,28] It has recently been demonstrated in an in vitro model that TLR signalling is involved in regulation of the intestinal barrier function[29], it is unknown whether these three L. plantarum strains have positive effects on intestinal mucosal barrier in human subjects after ingestion, or through which mechanisms these live bacterial organisms may improve the human gut barrier function. Aim of the present randomized, double-blind, placebo-controlled trial was to assess the effects of oral intake of the three L. plantarum strains over a 7-day period on small intestinal permeability, duodenal epithelial tight junction protein expression and mucosal gene transcription, in healthy human subjects
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