Abstract
Colorectal cancer is the third most prevalent cause of death among the different types of cancer worldwide, which relates to imbalance of the gut microbiota. Previous studies both in vitro and in vivo have shown that probiotics could prevent the development of colorectal cancer. The potential mechanisms responsible for anti-carcinogenic actions of probiotics include modification of the intestinal microbiota composition, changes in metabolic activity of the microbiota, binding and degrading of carcinogenic compounds, production of compounds with anti-carcinogenic activity, immunomodulation, improvement of the intestinal barrier, inhibition of cell proliferation and induction of apoptosis in cancer cells. Currently, postbiotics including probiotic culture supernatant, non-viable culture and metabolic activities have been suggested to provide the same effect as viable probiotic cells. This is the complete report of the second year during 2 September 2022 to 30 December 2023. The present study aimed to investigate the effect of probiotic product prototype containing L. paracasei SD1 and L. rhamnosus SD11 in combination in form of live and heat-killed compared to placebo in colorectal patients grade II and grade III. The investigations were included gut microbiome and immune responses. Of 30 patients with CRC grade II and grade III whom received standard treatment participated at the beginning, 28 (10 live-probiotic, 10 heat-killed and 8 placebo) completed the 6 months trial. Results showed that the levels of pro-inflammatory cytokines in serum included IL-1β, TNF-α, IL-6, IL-8 and IL-17A were significantly decreased among CRC patients received live- and heat-killed probiotics for 6 months compared to the beginning (p-value <0.001, 0.014, <0.001, 0.046, 0.035, for live probiotic group; and p-value <0.001, <0.001, <0.001, 0.005, 0.033, for heat-killed group respectively). In contrast, such levels in placebo group were significantly increased for IL-1β, TNF-α, and IL-8 after 6 months of intervention (p-value <0.001, <0.001, 0.001, respectively), and those were also significantly higher than the groups received probiotic products (p-value <0.001, <0.001, <0.001, respectively). Conversely, anti-inflammatory cytokines IL-10 and IL-12 were increased among patients in probiotic treatment (p-value = 0.004 and <0.001; p-value = 0.016 and <0.001, for live- and heat killed- probiotic, respectively). IL-10 and IL-12 were reduced in placebo group (p-value 0.039 and > 0.05, respectively). The short chain fatty acids, butyrate and propionate, levels in colonic fluids were significantly increased in all groups compared to the beginning (p <0.001). Those among patients who received heated killed products were significantly increased compared to placebo (p-value = 0.039 and <0.001, respectively) after 6 months of interventions. The short chain fatty acids in live probiotic group were higher placebo group, but it was not significant. The effect of probiotic interventions on gut microbiome was analyzed, the bacterial diversity tended to increase among the patients received live- and heat killed-probiotic products after 6 months. Gut microbiota, Bacteroides and Prevotella levels, together with Faecalibacterium, a butyrate producer, were higher among patients taking probiotic products than placebo group. Fusobacterium, an associated CRC bacterium, level was lower in probiotic groups than in placebo group. In conclusion, results in current study support on the application of the probiotics, L. paracasei SD1 and L. rhamnosus SD11 in combination, for improvement of CRC patients, adding new evidence for using probiotics and their clinical significance in vivo study.
