Bifidobacterium breve CNCM I-4035, Lactobacillus paracasei CNCM I-4034 and Lactobacillus rhamnosus CNCM I-4036 Modulate Macrophage Gene Expression and Ameliorate Damage Markers in the Liver of Zucker-Lepr fa/fa Rats.

Luis Fontana,Julio Plaza-Díaz,Paula Robles-Bolívar,Ángel Gil,María José Sáez-Lara,Héctor Valente-Godínez,Ana I Álvarez-Mercado,Francisco Abadía-Molina,Carolina Gómez-Llorente

doi:10.3390/nu13010202

Abstract

Non-alcoholic fatty liver disease (NAFLD) has reached pandemic proportions worldwide. We have previously reported that the probiotic strains Bifidobacterium breve CNCM I-4035, Lactobacillus paracasei CNCM I-4034 and Lactobacillus rhamnosus CNCM I-4036 exert anti-inflammatory effects in the intestine of Zucker-Leprfa/fa rats. In this work, we focused on their hepatic effects. M1 macrophages are related to inflammation and NAFLD pathogenesis, whereas M2 macrophages release anti-inflammatory mediators. We evaluated the effects of these 3 strains on macrophage polarization, inflammation and liver damage of Zucker-Leprfa/fa rats. The animals received either a placebo or 1010 CFU of probiotics orally for 30 days. Nos2 and Cd86 mRNA levels were determined as markers of M1 macrophages, and Cd163 and Arg1 as M2 markers, respectively, by qRT-PCR. Liver damage was determined by lipid peroxidation, leukocyte infiltration and myeloperoxidase activity. We evaluated a panoply of circulating chemokines, the hepatic ratio P-Akt/Akt, NF-kB and P-NF-kB protein levels. All 3 probiotic strains modulated macrophage polarization in liver and circulating levels of inflammation-related mediators. L. paracasei CNCM I-4034 increased the ratio P-Akt/Akt and NF-kB protein levels. B. breve CNCM I-4035, L. paracasei CNCM I-4034 and L. rhamnosus CNCM I-4036 decreased both pro-inflammatory macrophage gene expression and leukocyte infiltration in the liver.

Highlights

Non-alcoholic fatty liver disease (NAFLD) has reached pandemic proportions worldwide [1]
Beneficial effects of probiotics have been reported in allergy, intestinal-related diseases, chronic liver disease, urinary tract infections, and respiratory infections, among others
Lactobacilli and bifidobacteria are the genera most frequently used as probiotics, and they exert their benefits through a variety of mechanisms [23]

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) has reached pandemic proportions worldwide [1]. The liver is an immunologically complex organ due to its host non-lymphoid cells including stellate and dendritic cells, and lymphoid cells, macrophage Kupffer cells Many of these cells are components of the classic innate immune system, enabling the liver to play a major role in the response to pathogens [4]. Macrophages play central roles in host defense, immune regulation, tissue repair, and regeneration. They are generally delineated into 2 categories: M1 and M2 macrophages. M2 macrophages promote wound healing, angiogenesis, and resistance to parasites [6,7] This dichotomy is intimately associated with the great plasticity and remarkable heterogeneity of macrophages [8]

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