Adamdec1, Ednrb and Ptgs1/Cox1, inflammation genes upregulated in the intestinal mucosa of obese rats, are downregulated by three probiotic strains

Luis Fontana,María José Sáez-Lara,Ángel Gil,Alfonso Ruiz-Bravo,Francisco Abadía-Molina,Carolina Gómez-Llorente,Julio Plaza-Díaz,María Jiménez-Valera,Cándido Robles-Sánchez,Virginia Morón-Calvente

doi:10.1038/s41598-017-02203-3

Abstract

We have previously reported that administration of Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036 to obese Zucker-Leprfa/fa rats attenuates liver steatosis and exerts anti-inflammatory effects. The goal of the present work was to investigate the modulation of gene expression in intestinal mucosa samples of obese Zucker-Leprfa/fa rats fed the probiotic strains using a DNA microarray and postgenomic techniques. We also measured secretory IgA content in the gut and lipopolysaccharide (LPS)-binding protein (LBP) in serum. Expression of three genes (Adamdec1, Ednrb and Ptgs1/Cox1) was up-regulated in the intestinal mucosa of the obese rats compared with that in the rats when they were still lean. Probiotic administration down-regulated expression of Adamdec1 and Ednrb at the mRNA and protein levels and that of Ptgs1/Cox1 at the mRNA level, and this effect was in part mediated by a decrease in both macrophage and dendritic cell populations. Probiotic treatment also increased secretory IgA content and diminished the LBP concentration. Based on results reported in this work and else where, we propose a possible mechanism of action for these bacterial strains.

Highlights

Metabolic syndrome, better referred to as insulin resistance syndrome (IRS), was originally defined as concomitant hyperlipidemia, hypertension, insulin resistance and obesity[1, 2]
We have previously reported that the administration of three probiotic strains (Lactobacillus paracasei Collection Nationale de Cultures de Microorganismes (CNCM) I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036) to healthy human volunteers for 30 days is totally safe[11] and that their administration for the same period of time to obese Zucker rats attenuates the accumulation of fat in the rats’ liver and exerts anti-inflammatory effects such as lower serum concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and bacterial lipopolysaccharide (LPS)[5]
Our results show that L. paracasei CNCM I-4034, B. breve CNCM I-4035 and L. rhamnosus CNCM I-4036 were able to inhibit expression of Adamdec[1] and Ednrb at the mRNA and protein levels, as well as expression of Ptgs1/Cox[1] at the mRNA level, in the intestinal mucosa of the obese Zucker-Leprfa/fa rats

Summary

Introduction

Better referred to as insulin resistance syndrome (IRS), was originally defined as concomitant hyperlipidemia, hypertension, insulin resistance and obesity[1, 2]. Zucker-Leprfa/fa rats have hepatic steatosis, as well as elevated serum AST and ALT activities, indicating that the liver component of IRS is present in this model[5]. Ohtsuka et al.[10] administered Bifidobacterium breve M-16V to rat pups during the newborn period and found a lower expression of various inflammation-related genes in the colon. We have previously reported that the administration of three probiotic strains (Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036) to healthy human volunteers for 30 days is totally safe[11] and that their administration for the same period of time to obese Zucker rats attenuates the accumulation of fat in the rats’ liver and exerts anti-inflammatory effects such as lower serum concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and bacterial lipopolysaccharide (LPS)[5]

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Conclusion