A Novel Lactic Acid Bacteria Mixture: Macrophage-Targeted Prophylactic Intervention in Colorectal Cancer Management.

Petra Hradicka,Andrew Foey,Jane Beal,Monika Kassayova,Vlasta Demeckova

doi:10.3390/microorganisms8030387

Petra Hradicka, Andrew Foey + Show 3 more

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https://doi.org/10.3390/microorganisms8030387

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Abstract

Colorectal cancer (CRC) is one of the most common forms of cancer. Its onset from chronic inflammation is widely accepted. Moreover, dysbiosis plays an undeniable role, thus the use of probiotics in CRC has been suggested. They exhibit both anti- and pro-inflammatory properties and restore balance in the microbiota. The aim of this study was to investigate the immunomodulatory properties of six lactobacilli with probiotic features in an in vitro model of macrophage-like cells and to test these pooled probiotics for their anti-tumour properties in a chemically induced CRC model using Wistar male rats. Upon co-culture of M1- and M2-like macrophages with lactobacilli, cytokine release (TNF-α, IL-1β, IL-18, IL-23) and phagocytic activity using fluorescent-labelled bacteria were tested. The effects of orally administered probiotics on basic cancer and immune parameters and cytokine concentration (TNF-α, IL-1β, IL-18) in colon tumours were studied. Tested lactobacilli exhibited both pro- and anti-inflammatory properties in in vitro conditions. In vivo study showed that the administration of probiotics was able to decrease multiplicity, volume and total tumour numbers, restore colon length (p < 0.05) and increase IL-18 production (p < 0.05) in tumour tissue. These data indicate both an immunomodulatory effect of probiotics on distinct macrophage subsets and a protective effect against chemically-induced CRC.

Highlights

Due to its metabolic activity, the human microbiota is defined as a virtual organ that consists of more than 1013 cells, which are found lining the skin and mucosal surfaces such as the gastrointestinal tract
A similar trend was observed for IL-1β, especially in M2 macrophages, where cytokine release induced by LS strains MS3, MS6 and MS16 and the LP strain MS18 were the strongest within the panel of probiotic strains (Figure 1d)
In M1s, to M2s, the LS strains (MS16, MS3, MS6) showed the highest induction of this cytokine (Figure 1c). This trend of LS strains being the highest inducers of cytokine was repeated for M1 and M2 secretion of IL-18 (Figure 1e,f), whereas MS18, VD23 and C28 induced the smallest cytokine response

Summary

Introduction

Due to its metabolic activity, the human microbiota is defined as a virtual organ that consists of more than 1013 cells, which are found lining the skin and mucosal surfaces such as the gastrointestinal tract. There is, a strong correlation between dysbiosis and gut inflammation, as evidenced by a decreased proportion of Firmicutes and increased numbers of Bacteroides fragilis, B. vulgatus and bacteria from the Fusobacterium genus [9,10]. This dysbiosis can be redressed by probiotics, which in effect change the microbiota within the gastrointestinal tract into more favourable species [11]. Lactic acid bacteria (LAB) are the most frequently used [12] Apart from their ability to contribute to the inhibition of pathogens [13], they have been shown to have immunomodulatory effects [14,15]

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