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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.
AuthorsTao Wang, Jiaqi Zheng, Shuchen Dong, Mohamedelfaieh Ismael, Yuanyuan Shan, Xin Wang, Xin Lü
JournalProbiotics and antimicrobial proteins (Probiotics Antimicrob Proteins) Vol. 14 Issue 5 Pg. 947-959 (10 2022) ISSN: 1867-1314 [Electronic] United States
PMID35788907 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Chemical References
  • Dextran Sulfate
  • Azoxymethane
Topics
  • Animals
  • Azoxymethane (toxicity)
  • Carcinogenesis
  • Colitis (chemically induced, complications, drug therapy)
  • Dextran Sulfate (adverse effects)
  • Disease Models, Animal
  • Dysbiosis (drug therapy)
  • Gastrointestinal Microbiome
  • Inflammation (drug therapy)
  • Lacticaseibacillus rhamnosus
  • Mice

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