Soluble Mediators From Lactobacillus rhamnosus GG Reduce Intestinal Permeability And Bacterial Translocation In a Rat Model of Short Bowel Syndrome Model
Authors: Wu Jiang , Qian Linxi , Zhong Yan , Gross Gabriele , van Tol Eric , Lambers Tim , Cai Wei 
Published: November 2023

Objectives and study

The aim of this study was to evaluate the potential effects of specific preparations of soluble mediators derived from Lactobacillus rhamnosus GG (LGG) on intestinal barrier function in a rat model of short bowel syndrome (SBS).

Methods

6‐week old male SD rats were randomized into experimental groups (n=8). Sham operated rats underwent bowel transection and re‐anastomosis. The remaining animals underwent 75% small bowel resection and received either supplementation of 5*108 CFU viable LGG, two different LGG soluble mediator preparations in an equivalent dose only differing in the desalting methodology applied (ultrafiltration vs. column chromatography), or PBS by intragastric gavage daily from day 2 throughout day 14 after small bowel resection. Body weight of the animals was measured regularly. On day 15, intestinal permeability (fluorescein isothiocyanate‐dextran‐40,000 Daltons) and bacterial translocation to mesenteric lymph nodes, liver and spleen were measured. Serum levels of endotoxin were detected. TNF‐α and IL‐6 levels in ileum content and serum were determined by ELISA. Intestinal adaptation was evaluated by assessing villus height and crypt depth. Expression of tight junction proteins was measured by western‐blotting. Statistical analysis was performed using a one‐way ANOVA or a non‐parametric test.

Results

Compared with the sham operated group, rats with massive bowel resection showed significantly lower body weight, increased villus height and crypt depth. Weight gain was higher in all the intervention groups as compared to SBS control animals at the end of the experiment, with supplementation of the ultrafiltered soluble mediator preparation being particularly effective. Intestinal permeability, bacterial translocation, as well as endotoxin and cytokine levels were all affected in the SBS control group compared to sham operated animals. However, these were counteracted by the interventions, with supplementation of both LGG soluble mediator preparations leading to lower levels of FD‐40 than supplementation with viable LGG, and particularly the ultrafiltered preparation resulted in significantly lower endotoxin levels. The relative expression of occludin, ZO‐1, claudin‐1 and −4 in ileum was decreased after massive bowel resection, but this effect was ameliorated by supplementation with the specific LGG soluble mediator preparations.

Conclusions

Enteral supplementation of LGG or specific LGG derived soluble mediators improves intestinal permeability, reduces bacterial translocation, and lowers both systemic and local inflammation in a rat model of SBS. The LGG soluble mediators may not only mimic some of the biological effects of viable LGG, but may even show stronger activity in reducing inflammation and supporting intestinal barrier integrity, likely through up‐regulation of specific tight junction protein expression.

Support or Funding Information

The study was financially supported by Mead Johnson Nutrition.