Abstract
Propionibacterium freudenreichii is a commercially relevant bacterium with probiotic potential. This bacterium can exert protective effects particularly against colorectal cancer (CRC), via the production of short chain fatty acids (SCFA), namely acetate and propionate. In this work, we aimed to evaluate the performance and adaptation capacity of P. freudenreichii to a simulated digestive stress using different culture media, namely YEL, Basal medium, Mimicking the Content of the Human Colon medium (MCHC) and DMEM. The effect of the fermented culture broth on CRC cells survival and of CRC cells conditioned media on the bacteria performance was also evaluated. Basal medium was found to be the best for P. freudenreichii to produce SCFA. MCHC medium, despite being the medium in which lower amounts of acetate and propionate were produced, showed higher acetate and propionate yields as compared to other media. We also observed that the presence of lactate in CRC cells conditioned growth medium resulting from cell metabolism, leads to an increased production of SCFA by the bacteria. The bacterial fermented broth successfully inhibited CRC cells proliferation and increased cell death. Our results showed for the first time that P. freudenreichii performance might be stimulated by extracellular lactate produced by CRC metabolic switch also known as “Warburg effect,” where cancer cells “ferment” glucose into lactate. Additionally, our results suggest that P. freudenreichii could be potentially used as a probiotic in CRC prevention at early stages of the carcinogenesis process and might help in CRC therapeutic approaches.
Highlights
Colorectal cancer (CRC) constitutes a major concern in developed countries being associated to lifestyle which is emerging as a critical element for its prevention [1]
The acetate production was found to be around 1.65 ± 0.01; 1.81 ± 0.01; 0.58 ± 0.02, and 0.79 ± 0.02 g L−1 in yeast extract-lactate (YEL), BM, MCHC, and DMEM media, respectively; while the propionate production was around 4.69 ± 0.01; 4.81 ± 0.02; 1.37 ± 0.03, and 2.60 ± 0.05 g L−1 in YEL, BM, MCHC, and DMEM media, respectively
Our results suggest that P. freudenreichii promotes a cytotoxic effect on colorectal cancer (CRC) cells, via their metabolites, and that the CRC cells increases the acetate and propionate production by P. freudenreichii, which in turn will lead to an increased cytotoxic effect on the CRC cells
Summary
Colorectal cancer (CRC) constitutes a major concern in developed countries being associated to lifestyle which is emerging as a critical element for its prevention [1]. SCFA may have opposing effects either inducing/inhibiting autophagy and inhibiting proliferation of cancer cells or inducing apoptosis [24,25,26]. In this sense, our group has recently demonstrated that acetate induces lysosomal membrane permeabilisation and the release of Cathepsin D [22]. Lan et al [28] demonstrated in an in vivo study, that P. freudenreichii TL133, via its metabolites, facilitated the elimination of damaged cells by apoptosis in the rat colon after genotoxic insult and may play a protective role against CRC. We aimed to evaluate the influence of the bacteria medium on CRC cells survival and on the other hand the effect of CRC cells conditioned medium in bacteria performance in order to better understand the crosstalk between P. freudenreichii and CRC cells
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