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Screening and In-Vitro Analysis of Lactobacillus reuteri Strains for Short Chain Fatty Acids Production, Stability and Therapeutic Potentials in Colorectal Cancer

Kahouli I, Malhotra M, Tomaro-Duchesneau C, Saha S, Marinescu D, Rodes LS, Alaoui-Jamali MA and Prakash S

The use of probiotics as preventive agents in colorectal cancer is widely reported in the literature. However, the bioactivity of specific bacterial strains is only partially understood. Here, we identified Lactobacillus reuteri strains with anti-proliferative activity against colorectal cancer cells. We investigated the bioavailability and the efficacy of short chain fatty acids secreted by distinct Lactobacillus reuteri strains on the inhibition of colorectal cancer cells growth. Five L. reuteri strains were screened based on the short chain fatty acids bio-production and anti-proliferative effects on Caco-2 colon cancer cells. The composition of probiotic short chain fatty acids in cell culture conditioned medium was used to prepare short chain fatty acid synthetic formulations that were compared with the L. reuteri cell culture conditioned media. Later, the bio-stability of the bacteria in a simulated intestinal fluid was determined. Results showed that the production of short chain fatty acids was strain-dependent. L. reuteri NCIMB -11951, -701359 and -702656 were the most potent in producing total short chain fatty acids (402.2 ± 23. 5, p < 0.05 compared with the rest of strains) and inhibiting Caco-2 (by 56.7 ± 1.6 % compared to untreated cells at 72 h, p < 0.001). Comparing the inhibitory effect of the probiotic cell culture conditioned medium and the corresponding short chain fatty acid synthetic formulation showed that the role and relevance of short chain fatty acid production in colorectal cancer cell growth suppression was strain-dependent. L. reuteri NCIMB -702656 and -701359 showed resistance in simulated intestinal fluid (104.6 ± 0.6 % and 105.7 ± 4.1 % of viability at 4 h, respectively) and produced high amounts of total short chain fatty acids (1245.49 ± 0.49 - 1391.58 ± 4.84 mg/ L at 24 h, respectively). Depending partly on short chain fatty acid bio-production, specific L. reuteri strains demonstrated growth inhibitory activity and may be considered as a potential chemopreventive agent against colorectal cancer.