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Fermented milk, probiotics and yeast membrane constituents may prevent colorectal cancer

fermented-milk

Colorectal cancer (CRC) is the result of a series of histopathological changes starting with the appearance of outbreaks of aberrant crypts (AC) in the colon and generally leading to adenocarcinoma. CRC is one of the third most common diagnosed cancers in western countries.

Diet and lifestyle have important roles in preventing CRC and still seem to be the most efficient approach. Numerous epidemiological studies have associated a high incidence of CRC with the “western pattern diet” – a diet with a higher intake of red and/or processed meat, processed food, sweets and a lower intake of fruits, vegetables and dietary fibre. Modulating the eating habits and consumption of diet containing agents with CRC preventive properties could decrease or prevent the risk of developing CRC (Fortin et al., 2017, Desrouilles et al., 2016, Randi et al., 2010).

Cancer prevention could occur via cancer cell cytotoxicity, apoptosis, antioxydant and/or enzymatic modulation. For example, quinone reductase (QR), a phase II detoxification enzyme protects against toxic metabolites involved in the first stage of carcinogenesis process and decreases chemical carcinogenicity compounds by transforming them into compounds with less toxicicity. Glutathione-S-transferase (GST) can protect cells against toxicants by conjugating the thiol group of the glutathione to electrophilic xenobiotics and β-glucuronidase enzymes can release carcinogenic compounds in the colon. A reduction in its activity can lead to reduced exposure to carcinogenic substance.

Besides the diet, the presence of some bacteria increases the risk of the disease, suggesting a strong link between CRC and colon microflora (Kado et al., 2001). A commercial fermented milk produced by Bio-K Plus International Inc., containing Lactobacillus acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2, was evaluated for its anticancer properties.

An in vivo study in rats found that those fed with fermented milk (FM) had a reduction in the total count of aberrant crypt (AC) in the colon and the total number of aberrant crypt foci (ACF) of 43% compared to the carcinogen control group. Rats fed with the supernatant of the fermented milk (S) and the pellet of the fermented milk (P) were able to reduce the count of AC and the number of ACF by more than 50%. Also, rats fed with the cell wall of the probiotic (CW) had a 34% reduction of the total count of AC and a 20% reduction of ACF.

The number of AC/ACF was also evaluated and results showed that rats fed with FM had a complete elimination of the number of foci containing 4 or 5 aberrant crypts. Rats fed with (S) and (CW) were able to reduce the number of crypt per foci in the group 4-5 aberrant crypts by more than 90%. Also, rats fed with (S) or (P) had close to a 60% reduction of the count of AC per focus in the 2-3AC/ACF. The probiotic bacteria mixture was able to increase the activity of the GST by more than 50% and the cell walls were able to increase the level of QR enzymes by 50%. The probiotic bacteria mixture, the whole fermented milk or the pellet of the bacteria were also able to reduce the activity of β-glucosidase by 35-40% (Desrouilles et al., 2015, 2016).

Saccharomyces boulardii and Kluyveromyces marxianus are well-known yeasts in food industry. Their membranes are composed of insoluble (47%)/soluble glucan (36%) and mannoprotein (0.45%). Our studies found that mannoprotein of K. marxianus exhibits the most relevant antioxidant activity – probably due to the presence of aromatic amino acids and thiol groups. However, only insoluble glucan from both yeast species can induce QR enzyme activity. Cell wall extracts of both yeast cells are able to inhibit in vitro growth of HT 29 colon cancer cells by more than 50% but extracts of S. boulardii were the most efficient.

In vivo studies with rats demonstrate that ingestion of crude insoluble glucan (0∙5mg kg-1 day-1), obtained from S. boulardii cell walls exhibit colon cancer prevention properties, with enzymatic modulation being one of the mechanisms observed. An induction of more than 68% of the QR specific activity and a reduction of more than 50% of the β-glucuronidase activity was found. Furthermore, a reduction of more than 45% of the total count of aberrant crypt (AC), 50% of aberrant crypt foci (ACF) and 73% of the total number of ACF containing 4-5 AC per focus in the animal colon was observed (Fortin et al., 2017).

Our study suggests that the whey and casein-derived peptides, exopolysaccharides, probiotics and their cells walls could individually exert a cancer-preventing effect by reducing and eventually inhibiting the formation of ACF. Extraction of yeast cell walls of probiotic bacteria or S. boulardii and K. marxianus yeasts via simple and fast extraction are promising in the development of new nutraceutical products.

monique-lacroix-2


Monique Lacroix
, Professor and Director of the Research Laboratories in Sciences at the INRS-Institut Armand-Frappier, will be speaking on preventing cancer with nutraceuticals at the upcoming Probiotics Congress: USA.

Hear about advances in probiotic product development and regulation from leaders in the field – register now for the 2nd Probiotics Congress: USA.

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