Effect of Bifidobacterium animalis subsp. lactis SF on enhancing the tumor suppression of irinotecan by regulating the intestinal flora

Pharmacol Res. 2022 Oct:184:106406. doi: 10.1016/j.phrs.2022.106406. Epub 2022 Aug 18.

Abstract

The gut microbiota plays a role in tumor therapy by participating in immune regulation. Here, we demonstrated through 8-day probiotic supplementation experiments and fecal microbiota transplantation experiments that Bifidobacterium animalis subsp. lactis SF enhanced the antitumor effect of irinotecan and prevented the occurrence of intestinal damage by modulating the gut microbiota and reducing the relative abundance of pro-inflammatory microbiota. Therefore, the intestinal inflammation was inhibited, the TGF-β leakage was reduced, and the PI3K/AKT pathway activation was inhibited. Thus, the tumor apoptotic autophagy was finally promoted. Simultaneously, the reduction of TGF-β relieved the immunosuppression caused by CPT-11, promoted the differentiation of CD4+ and CD8+ T cells in tumor tissue, and consequently inhibited tumor growth and invasion. This study disclosed the mechanism of B. lactis SF assisting CPT-11 in antitumor activity and suggested that B. lactis SF plays a new role in anticancer effects as a nutritional intervention.

Keywords: B. lactis SF; Intestinal barrier; Intestinal flora; Irinotecan; PI3K/AKT pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bifidobacterium animalis*
  • CD8-Positive T-Lymphocytes
  • Gastrointestinal Microbiome*
  • Irinotecan / pharmacology
  • Phosphatidylinositol 3-Kinases
  • Probiotics* / therapeutic use
  • Proto-Oncogene Proteins c-akt
  • Transforming Growth Factor beta

Substances

  • Transforming Growth Factor beta
  • Irinotecan
  • Proto-Oncogene Proteins c-akt