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

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

Author information

1
Department of Oncology, the First Affiliated Hospital of Dalian Medical University, Dalian, China.
2
Department of Oral and Maxillofacial Surgery, Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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

PMID:
28848081
DOI:
10.1159/000480005
[Indexed for MEDLINE]
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