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 (150mg.kg(-1)) was administered by a single intraperitoneal injection on day 0; animals were killed on day 4. 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: villous 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 ANOVA statistical analyses were conducted for the majority of outcome measures. Live TH-4 significantly reduced disease severity score by 13% (p< 0.05), and partially normalised 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 normalised 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 characterised by increased crypt fission, such as colorectal carcinoma.

Although chemotherapy remains the current best practice for the treatment of neoplasia, the severity of its associated side-effects continues to impact detrimentally on the quality of life. Mucositis can affect both the oral cavity and intestine, and represents one of the most common side-effects of chemotherapy. It is characterized by ulceration, inflammation, diarrhoea, and intense abdominal pain. Despite extensive research there remains no definitive therapy for mucositis. This may be due to the multiple factors which contribute to its pathogenesis, including up-regulation of pro-inflammatory cytokines, increased apoptosis of epithelial cells, alteration of the gastrointestinal microbiota, and damage to the epithelium. Although employed increasingly in other gastrointestinal disorders, probiotics are yet to be comprehensively investigated in the treatment or prevention of chemotherapy-induced mucositis. Probiotic-based therapies have been shown to exert beneficial effects, including modulation of the microbiota and inhibition of pro-inflammatory cytokines. This review outlines the current evidence supporting the use of probiotics in intestinal mucositis, and suggests further research directions for the future.

No abstract

No abstract

The potential efficacy of a probiotic-based preventative strategy against intestinal mucositis has yet to be investigated in detail. We evaluated supernatants (SN) from Escherichia coli Nissle 1917 (EcN) and Lactobacillus rhamnosus GG (LGG) for their capacity to prevent 5-fluorouracil (5-FU)-induced damage to intestinal epithelial cells. A 5-day study was performed. IEC-6 cells were treated daily from days 0 to 3, with 1 mL of PBS (untreated control), de Man Rogosa Sharpe (MRS) broth, tryptone soy roth (TSB), LGG SN, or EcN SN. With the exception of the untreated control cells, all groups were treated with 5-FU (5 μM) for 24 h at day 3. Transepithelial electrical resistance (TEER) was determined on days 3, 4, and 5, while activation of caspases 3 and 7 was determined on days 4 and 5 to assess apoptosis. Pretreatment with LGG SN increased TEER (p < 0.05) compared to controls at day 3. 5-FU administration reduced TEER compared to untreated cells on days 4 and 5. Pretreatment with MRS, LGG SN, TSB, and EcN SN partially prevented the decrease in TEER induced by 5-FU on day 4, while EcN SN also improved TEER compared to its TSB vehicle control. These differences were also observed at day 5, along with significant improvements in TEER in cells treated with LGG and EcN SN compared to healthy controls. 5-FU increased caspase activity on days 4 and 5 compared to controls. At day 4, cells pretreated with MRS, TSB, LGG SN, or EcN SN all displayed reduced caspase activity compared to 5-FU controls, while both SN groups had significantly lower caspase activity than their respective vehicle controls. Caspase activity in cells pretreated with MRS, LGG SN, and EcN SN was also reduced at day 5, compared to 5-FU controls. We conclude that pretreatment with selected probiotic SN could prevent or inhibit enterocyte apoptosis and loss of intestinal barrier function induced by 5-FU, potentially forming the basis of a preventative treatment modality for mucositis.

Inflammatory bowel disease (IBD) is a chronic relapsing disorder that is increasing in prevalence in Western society and has been linked to the development of colorectal cancer. There remains no definitive treatment for IBD, hence recent investigations have focused on the development of new therapeutics, including probiotics, which can reduce intestinal inflammation and restore balance to the gastrointestinal microbiota. Probiotics are currently being studied in greater detail, albeit predominantly in animal models of IBD. Clinical studies have yielded promising findings and justify further investigation. Furthermore, the use of inactivated probiotics as well as the soluble products produced by these bacteria has demonstrated therapeutic potential, and may in fact be more suitable, as there is no risk of sepsis associated with their administration and they can be manufactured with greater quality control. Further research is essential to define the mechanism and source of probiotic action, and to identify more efficacious strains, while future clinical trials must focus on determining whether the bacterial and genetic profiles of IBD patients influence the effectiveness of treatment.

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the

No abstract