Abstract
The metabolites produced by the host’s gut microbiota have an important role in the maintenance of intestinal homeostasis, but can also act as toxins and induce DNA damage in colorectal epithelial cells increasing the colorectal cancer (CRC) chance. In this scenario, the impact of some of the components of the natural human gastrointestinal microbiota, such as Enterococcus faecalis (E. faecalis), at the onset of CRC progression remains controversial. Since under dysbiotic conditions it could turn into a pathogen, the aim of this study was to compare the effect of E. faecalis’ strains (isolated from CRC patients and healthy subjects’ stools) on the proliferation of different colorectal cells lines. First, we isolated and genotyping characterized the Enterococcus faecalis’ strains. Then, we analyzed the proliferation index (by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay) of three tumor and one normal intestinal cell lines, previously exposed to E. faecalis strains pre-cultured medium. Stool samples of CRC patients demonstrated a reduced frequency of E. faecalis compared to healthy subjects. In addition, the secreted metabolites of E. faecalis’ strains, isolated from healthy donors, decreased the human ileocecal adenocarcinoma cell line HCT-8 and human colon carcinoma cell line HCT-116 cell proliferation without effects on human colorectal adenocarcinoma cell line SW620 and on normal human diploid cell line CLR-1790. Notably, the metabolites of the strains isolated from CRC patients did not influence the cell growth of CRC cell lines. Our results demonstrated a new point of view in the investigation of E. faecalis’ role in CRC development, which raises awareness of the importance of not only associating the presence/absence of a unique microorganism, but also in defining the specific characteristics of the different investigated strains.
Highlights
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers among both men and women worldwide, being the third most frequent in many high-income countries, with an estimated more than 100,000 new cases expected in 2018 [1]
The presence of E. faecalis was investigated in the feces of healthy donors (HD) and CRC patients (CC) (Table 1) through two complementary approaches
Our observations were restricted to a limited number of subjects, the remarkable differences disclosed between CRC patients and healthy donors suggest that the majority of CRC patients possibly lose the physiological stool presence of E. faecalis that we supposed to have a protective role on gut health
Summary
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers among both men and women worldwide, being the third most frequent in many high-income countries, with an estimated more than 100,000 new cases expected in 2018 [1]. The CRC incidence in low-income countries is closely related with differences in lifestyle [2,3], with only 15% of cases having a familial feature, whereas sporadic forms represent 85% [4] Environmental factors, such as smoking, alcoholism, obesity, sedentary lifestyle, consumption of red meat, high-fat diet, and inadequate fiber intake, are closely involved in the CRC onset and progression [5]. All these risk factors have a modulating role on the host gut microbiota (GM) composition, whose effects on CRC progression/protection have been investigated during the last years [6,7]. The GM members can modulate the mucosal immune system, as well as directly change the expression of some host genes associated with nutrient uptake, metabolism, angiogenesis, and mucosal barrier functions [9,10]
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