Lacticaseibacillus rhamnosus LS8 Ameliorates Azoxymethane/Dextran Sulfate Sodium-Induced Colitis-Associated Tumorigenesis in Mice via Regulating Gut Microbiota and Inhibiting Inflammation

Abstract

Gut microbiota dysbiosis may promote the process of colorectal cancer (CRC). Lacticaseibacillus rhamnosus LS8 (LRL) is a potential gut microbiota regulating strain because it can produce a novel antimicrobial substance (like cycloalanopine). In addition, this probiotic had an inflammation-ameliorating effect on the dextran sulfate sodium (DSS)-induced colitis mice. However, it is not known whether treatment with this probiotic could ameliorate colitis-associated CRC via regulating gut microbiota. In this study, a CRC mouse model was induced by a single intraperitoneal injection of azoxymethane (AOM, 10 mg/kg) and followed by three 7-day cycles of 2% DSS administration. Results showed that LRL could inhibit tumor formation. Moreover, LRL enhanced the gut barrier by preventing goblet cell loss and promoting the expression of ZO-1, occludin, and claudin-1. Furthermore, LRL ameliorated gut microbiota dysbiosis, which was conducive to the growth of beneficial bacteria (e.g., Faecalibaculum and Akkermansia), and further led to an increase in SCFAs and a decrease in LPS. In addition, LRL alleviated colonic inflammation by inhibiting the overexpression of TLR4/NF-κB, pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-γ, and IL-17a), and chemokines (Cxcl1, Cxcl2, Cxcl3, Cxcl5, and Cxcl7). In conclusion, LRL could alleviate CRC by regulating gut microbiota and preventing gut barrier damage and inflammation.

Keywords: Colorectal cancer; Gut barrier; Gut microbiota; Inflammation; Lacticaseibacillus rhamnosus.