Parabacteroides johnsonii Inhibits the Onset and Progression of Colorectal Cancer by Modulating the Gut Microbiota

Background Colorectal cancer (CRC) is the third most prevalent malignant tumor and the second leading cause of cancer-related deaths globally. The genus Parabacteroides is an important component of the gut microbiota. P. distasonis and P. goldsteinii are reported probiotics, and their roles in CRC have been investigated in related studies. However, the association between P. johnsonii and CRC remains unknown. Methods P. johnsonii (10–42) and Lactococcus formosensis (22–2) were isolated from healthy human feces. 25 mice that demonstrated normal feeding and activity were randomly assigned to four groups : normal control (NC group), CRC model (IC group), P. johnsonii (PJ group), and L. formosensis (LO group). Colonic tumor tissues from the IC, PJ, and LO groups and normal colon tissues from the NC group were then collected for HE staining and immunohistochemical staining. Fecal samples from mice during the hyperproliferative and adenoma phases were collected for Metagenomic sequencing and metabolite analysis. Results P. johnsonii intervention reduced the number and slowed the growth of colonic tumors, improved tumor histological scores, and decreased microenvironmental inflammation levels. P. johnsonii improved the composition of intestinal flora in mice with colon cancer, increased gut microbial species diversity, and maintained gut microbiota stability. Furthermore, P. johnsonii intervention increased the abundance of Bifidobacterium pseudolongum and Lactobacillus, which play a role in ameliorating AOM/DSS-induced gut microbiota dysbiosis. P. johnsonii intervention affected the metabolic pathways, including amino sugar degradation and galactose metabolism, sphingolipid synthesis, amino acid synthesis, and polyphenol synthesis pathways, with the tryptophan metabolism pathway as the primary pathway being affected. Conclusion Our study profiled the P. johnsonii administration reduces the number of tumors and lower tumor staging in AOM/DSS-induced colon cancer mice by modulating gut microbiota and its metabolites at early stages.