Abstract
The gut microbiota plays a major role in intestinal health, and an imbalance in its composition can lead to chronic gut inflammation and a predisposition to developing colorectal cancer (CRC). Currently, the use of probiotic bacteria represents an emerging alternative to treat and prevent cancer. Moreover, consumption of these beneficial bacteria may also favorably modulate the composition of the gut microbiota, which has been described in several studies to play an important role in CRC carcinogenesis. In this context, the aim of this study was to assess the protective effect of oral treatment with Lactobacillus casei BL23, a probiotic strain well known for its anti-inflammatory and anticancer properties. First, CRC was induced in C57BL6 mice by a single intraperitoneal injection with azoxymethane (8 mg/kg), followed by four courses of dextran sodium sulfate (2.5%) in drinking water that were separated by an adjustable recovery period. At the time of sacrifice (day 46), tumor incidence, histological scores, and epithelial proliferation were determined in colon samples. Our results show that L. casei BL23 significantly protected mice against CRC development; specifically, L. casei BL23 treatment reduced histological scores and proliferative index values. In addition, our analysis revealed that L. casei BL23 had an immunomodulatory effect, mediated through the downregulation of the IL-22 cytokine, and an antiproliferative effect, mediated through the upregulation of caspase-7, caspase-9, and Bik. Finally, L. casei BL23 treatment tended to counterbalance CRC-induced dysbiosis in mice, as demonstrated by an analysis of fecal microbiota. Altogether our results demonstrate the high potential of L. casei BL23 for the development of new, probiotic-based strategies to fight CRC.
Highlights
Colorectal cancer (CRC) is a major public health problem and is considered the third most common cancer around the world, with nearly 1.2 million new cases every year and a mortality rate of ~40% [1]
To determine the potential beneficial effects of the dairy strain BL23 of L. casei on colorectal cancer (CRC) onset, live bacteria were orally administered to mice treated with AOM and dextran sodium sulfate (DSS)
Ki67 levels were significantly lower (p = 0.044, Student’s t-test) in mice treated with L. casei BL23 than in control mice (Figures 3D,E)
Summary
Colorectal cancer (CRC) is a major public health problem and is considered the third most common cancer around the world, with nearly 1.2 million new cases every year and a mortality rate of ~40% [1]. The beneficial role of probiotic bacteria against CRC onset may be explained by three different mechanisms: (i) modulation of the immune response, (ii) induction of cell apoptosis, or (iii) antioxidant activity [reviewed in Ref. The food supplement VSL#3 (a mixture of eight probiotic bacteria) has been shown to modulate the immune response and reduce adenoma development in a model of CRC induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) [12]. Lactobacillus gasseri and Bifidobacterium longum have been shown to inhibit cellular proliferation and increase phagocytic activity in a model of 1,2-dimethylhydrazine (DMH)-associated CRC and reduce the multiplicity of aberrant crypt foci as well as tumor size [13]. The probiotic strain Lactobacillus casei Shirota is able to suppress chemically induced intradermal tumor onset through both an enhancement of the cytotoxicity of natural killer (NK) cells [14] and IL-12 release by dendritic cells [15]
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