Bifidobacterium Infantis Ameliorates Chemotherapy-Induced Intestinal Mucositis Via Regulating T Cell Immunity in Colorectal Cancer Rats

Cell Physiol Biochem. 2017;42(6):2330-2341. doi: 10.1159/000480005. Epub 2017 Aug 18.

Abstract

Background/aims: Intestinal mucositis (IM) is a commonly encountered side effect in cancer patients receiving chemotherapy. This study aimed to investigate the effect of Bifidobacterium infantis (B. infantis) in attenuating the severity of chemotherapy-induced intestinal mucositis by regulating the T cell subsets in rats with colorectal cancer (CRC).

Methods: Thirty male Sprague-Dawley (SD) rats were injected dimethyl hydrazine (DMH) subcutaneously for 10 weeks, and then injected SW480 cells in rectal mucosa to create a CRC model, and the rats were randomly divided into three groups: Control group (saline + saline), Chemotherapy group (saline + 5-FU+Oxaliplatin), B. infantis group (B. infantis + 5-FU+Oxaliplatin). IM was evaluated based on diarrhea severity, intestinal villus height, crypt depth, pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), T cell subsets (CD4+ IL17A+ cells and CD4+ CD25+ Foxp3+ Tregs) and related cytokine profiles.

Results: The results showed that the B. infantis group demonstrated a higher body weight (BW) and intestinal villus height and a deeper crypt depth compared to the Chemotherapy group. The level of IL-6, IL-1β and TNF-α which increased by chemotherapy, was lowered by B. infantis administration. Real time reverse transcription- polymerase chain reaction (RT-PCR) showed B. infantis reduced relative expression of Th17 and Th1 cells related cytokines, and increased relative expression of CD4+ CD25+ Foxp3+ Tregs related cytokines. Furthermore, Flow cytometry analysis showed B. infantis reduced CD4+ IL17A+ cells and increased CD4+ CD25+ Foxp3+ Tregs in mesenteric lymph nodes (MLNs) compared to the Chemotherapy group.

Conclusion: B. infantis effectively attenuates chemotherapy-induced intestinal mucositis by decreasing Th1 and Th17 response and increasing CD4+ CD25+ Foxp3+ Tregs response.

Keywords: 5-fluorouracil; Bifidobacterium infantis; CD4+CD17A+ cells; CD4+CD25+Foxp3+ Tregs; Colorectal cancer; Intestinal mucositis; Oxaliplatin.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents / toxicity
  • Bifidobacterium longum subspecies infantis / physiology*
  • Cell Line
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / pathology
  • Cytokines / blood
  • Cytokines / genetics
  • Cytokines / metabolism
  • Diarrhea / pathology
  • Disease Models, Animal
  • Fluorouracil / therapeutic use
  • Fluorouracil / toxicity
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Male
  • Mucositis / chemically induced
  • Mucositis / metabolism
  • Mucositis / pathology
  • Organoplatinum Compounds / therapeutic use
  • Organoplatinum Compounds / toxicity
  • Oxaliplatin
  • Probiotics / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Th1 Cells / cytology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th17 Cells / cytology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism

Substances

  • Antineoplastic Agents
  • Cytokines
  • Organoplatinum Compounds
  • Oxaliplatin
  • Fluorouracil