Effects of Streptococcus thermophilus TH-4 on intestinal mucositis induced by the chemotherapeutic agent 5-Fluorouracil (5-FU)

摘要

Beneficial bacteria (probiotics) and probiotic-derived factors have the potential to ameliorate disorders of the intestine. The aim of this study was to compare live Streptococcus thermophilus TH-4 (TH-4), dead TH-4 and TH-4 supernatant in rats treated with 5-Fluorouracil. Rats were randomly allocated to five treatment groups (n = 8-10): Saline + Water; 5-FU + Skim Milk; 5-FU + Live TH-4; 5-FU + Supernatant TH-4; and 5-FU + Dead TH-4. 5-FU (150 mg.kg~(-1)) was administered by a single intraperitoneal injection on day zero; animals were killed on day four. Treatments were administered daily from days -2 to +3 via oro-gastric gavage. Metabolic parameters were measured daily. Blood was obtained by cardiac puncture, and intestinal tissues removed for quantitative and qualitative histological assessment, including: villus height and area; crypt depth and area, mitotic count and crypt fission; biochemical determination of sucrase and myeloperoxidase (MPO) activity, and disease severity scoring. One-way ANOYA statistical analyses were conducted for the majority of outcome measures. Live TH-4 significandy reduced disease severity score by 13% (p < 0.05), and partially normalized mitotic counts compared with 5-FU + Skim Milk controls. Live and Supernatant TH-4 reduced crypt fission by 69% and 48% (p < 0.05), respectively, compared to 5-FU + Skim Milk controls. No significant differences (p > 0.05) in the occurrence of bacteraemia were evident across all groups. Live TH-4 partially normalized mitotic count and histological severity score in 5-FU treated rats. The inhibitory effect of live TH-4 and TH-4 Supernatant on crypt fission suggests therapeutic utility in the prevention of disorders characterized by increased crypt fission, such as colorectal carcinoma.