Evaluation of the Immunomodulatory Activities of the Probiotic Strain Lactobacillus fermentum UCO-979C

Valeria Garcia-Castillo,Patricia Clua,Haruki Kitazawa,Apolinaria Garcia-Cancino,Yuhki Indo,Julio Villena,Susana Salva,Michihiro Takagi,Ryoya Komatsu,Hideki Takahashi,Susana Alvarez,Md Aminul Islam

doi:10.3389/fimmu.2019.01376

Abstract

Lactobacillus fermentum UCO-979C, a strain isolated from a human stomach, was previously characterized by its potential probiotic properties. The UCO-979C strain displayed the ability to beneficially regulate the innate immune response triggered by Helicobacter pylori infection in human gastric epithelial cells. In this work, we conducted further in vitro studies in intestinal epithelial cells (IECs) and in vivo experiments in mice in order to characterize the potential immunomodulatory effects of L. fermentum UCO-979C on the intestinal mucosa. Results demonstrated that the UCO-979C strain is capable to differentially modulate the immune response of IECs triggered by Toll-like receptor 4 (TLR4) activation through the modulation of TLR negative regulators' expression. In addition, we demonstrated for the first time that L. fermentum UCO-979C is able to exert its immunomodulatory effect in the intestinal mucosa in vivo. The feeding of mice with L. fermentum UCO-979C significantly increased the production of intestinal IFN-γ, stimulated intestinal and peritoneal macrophages and increased the number of Peyer's patches CD4+ T cells. In addition, L. fermentum UCO-979C augmented intestinal IL-6, reduced the number of immature B220+CD24high B cells from Peyer's patches, enhanced the number of mature B B220+CD24low cells, and significantly increased intestinal IgA content. The results of this work revealed that L. fermentum UCO-979C has several characteristics making it an excellent candidate for the development of immunobiotic functional foods aimed to differentially regulate immune responses against gastric and intestinal pathogens.

Highlights

It is widely recognized that commensal microorganisms are relevant for human and animals health, participating in several important biological functions including nutrients digestion, vitamins synthesis, and pathogens inhibition [1, 2]
PIE cells were treated with lactobacilli and challenged with heatstable Enterotoxigenic Escherichia coli (ETEC) pathogen associated molecular patterns (PAMPs) that are able to trigger Toll-like receptor 4 (TLR4) activation in this cell line [25, 26]
We previously reported that L. fermentum UCO-979C modulates the innate immune response in human gastric epithelial cells and macrophages, and improves protection against H. pylori infection [23]

Summary

Introduction

It is widely recognized that commensal microorganisms are relevant for human and animals health, participating in several important biological functions including nutrients digestion, vitamins synthesis, and pathogens inhibition [1, 2]. Several effective tools have already been developed in order to study and manipulate the microbiota, improve their beneficial properties for the host, and protect against immune-related diseases [5, 6]. In this regard, the development of immunomodulatory probiotic (immunobiotic) interventions offers opportunities for the modulation of the mucosal immune system toward long lasting health [7]. Several research works including recent transcriptomic analysis revealed that the immunomodulatory effect of immunobiotics is a strain-specific characteristic [2, 12, 15], and each individual strain has to be studied in detail in order to explore its immunomodulatory potential

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