Klebsiella aerogenes exacerbates colon tumorigenesis in the AOM/DSS-induced C57BL/6J mouse

Biochem Biophys Res Commun. 2024 Jan 29:694:149410. doi: 10.1016/j.bbrc.2023.149410. Epub 2023 Dec 19.

Abstract

Klebsiella aerogenes (K. aerogenes, KA) is a gram-negative opportunistic pathogen from the Klebsiella species and the Enterobacteriaceae family. However, the impact of K. aerogenes on colorectal cancer (CRC) remains uncertain. A colitis-associated tumorigenesis animal model was established by administering azoxymethane (AOM) and dextran sulfate sodium (DSS) to C57BL/6J mice. The concentration of K. aerogenes gavage in mice was 109 cfu. The study measured the following parameters: tumor formation (number and size), intestinal permeability (MUC2, ZO-1, and Occludin), colonic inflammation (TNF-α, IL-1β, IL-6, and IL-10), proliferation and the fluctuation of the intestinal flora. Under the AOM/DSS-treated setting, K. aerogenes colonization worsened colitis by exacerbating intestinal inflammatory reaction and destroying the mucosal barrier. The intervention markedly augmented the quantity and dimensions of neoplasm in the AOM/DSS mice, stimulated cellular growth, and impeded cellular programmed cell death. In addition, K. aerogenes exacerbated the imbalance of the intestinal microbiota by elevating the abundance of Pseudomonas, Erysipelatoclostridium, Turicibacter, Rikenella, and Muribaculum and leading to a reduction in the abundance of Odoribacter, Alloprevotella, Roseburia, and Lachnospiraceae_NK4A136_group. The presence of K. aerogenes in AOM/DSS-treated mice promoted tumorigenesis, worsened intestinal inflammation, disrupted the intestinal barrier, and caused disturbance to the gut microbiota.

Keywords: Colorectal cancer; Inflammation; Intestinal barrier; Intestinal microbiota; Klebsiella aerogenes.

MeSH terms

  • Animals
  • Azoxymethane / metabolism
  • Azoxymethane / toxicity
  • Bacteroidetes
  • Carcinogenesis / pathology
  • Cell Transformation, Neoplastic / pathology
  • Colitis* / pathology
  • Colon / pathology
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Enterobacter aerogenes*
  • Inflammation / pathology
  • Mice
  • Mice, Inbred C57BL

Substances

  • Azoxymethane
  • Dextran Sulfate