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

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.

• Authors: Hui Mi, Yan Dong, Bin Zhang, Haonan Wang, Chung C K Peter, Ping Gao, Hong Fu, Yajie Gao
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 42 Issue 6 Pg. 2330-2341 ( 2017) ISSN: 1421-9778 [Electronic] Germany
• PMID: 28848081 (Publication Type: Journal Article)
• Copyright: © 2017 The Author(s). Published by S. Karger AG, Basel.

Chemical References

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

Topics

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