Inflammasomes and colorectal cancer: new insights in probiotics

A brief of a postgraduate intern’s thesis. I provided research to writing guidance throughout the work.

The study was performed to show the therapeutic point of view for future functional food strategy in chemoprevention and cancer growth inhibition from the indigenous probiotic Lactobacillus plantarum CRD7 strain. The study found evident results from enhanced antiproliferative efficacy showing the therapeutic potential of CRD7  in the activation of host-derived factors such as inflammasomes and mediators of inflammation in three human grade cell lines of colorectal cancer HT-29, HCT-116 and SW480. This was the first report to show a connection between probiotics and activation of various inflammasomes such as NLRP3, NLRC4, and NAIP5 through caspase-1 dependent or caspase-1 independent pathways in these cell lines. Treatment of CRD7 strain activates the NLRP3 inflammasome which leads to the production of IL-18 and IL-1β, participating in the regulation of intestinal inflammation and colorectal carcinogenesis. Lactobacillus plantarum produces lipoteichoic acid (LTA), which reportedly reduces lipopolysaccharides (LPS) induced tumor necrosis factor-α (TNF-α) production. From the results, treatment of live probiotic bacteria significantly upregulated the mRNA expression of TLR9 and cGAS markers at all the time points of experimental set up which could also lead to the activation of NF-kB, inflammasome, and interferon signaling pathways, respectively. Based on results, TLR-9 mediated recognition of probiotic bacteria and its components in the human colon cancer cells exerts a protective effect against inflammation. Although the physiological relevance of sensing mechanisms by cGAS during intestinal inflammation has not been investigated to date and this study demonstrates the involvement of NLRP3 inflammasomes dependent activation of the mucosal immune system, which critically provides protection against inflammation. Furthermore, the therapeutic effects of CRD7 totally diminished with the heat-killed treatment at all time points in the cell lines. Therefore, the study showed a protective role of probiotics in the activation of inflammasomes and regulation of inflammation in colorectal cancer via production of antimicrobial effector molecules, offering an insight into the pathogenesis of gut inflammatory disorders where probiotics may serve as a therapeutic option for the regulation of inflammation and ameliorates inflammatory responses in colorectal cancer.

Note: I will shortly provide a brief and a link to the mother article which inspired this research.


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