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

• Main Authors: Hui Mi, Yan Dong, Bin Zhang, Haonan Wang, Chung C.K. Peter, Ping Gao, Hong Fu, Yajie Gao
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2017-08-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Bifidobacterium infantis; Intestinal mucositis; 5-fluorouracil; Oxaliplatin; CD4+CD25+Foxp3+ Tregs; CD4+CD17A+ cells; Colorectal cancer
• Online Access: http://www.karger.com/Article/FullText/480005
• ISSN: 1015-8987; 1421-9778

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.