title: Effects of Streptococcus thermophilus TH-4 on intestinal mucositis induced by the chemotherapeutic agent, 5-Fluorouracil (5-FU).
abstract: 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.
authors.affiliation: Centre for Paediatric and Adolescent Gastroenterology, Children, Youth and Women's Health Service, North Adelaide, South Australia.
authors.forename: Eleanor J
authors.initials: EJ
authors.lastname: Whitford
authors.forename: Adrian G
authors.initials: AG
authors.lastname: Cummins
authors.forename: Ross N
authors.initials: RN
authors.lastname: Butler
authors.forename: Luca D
authors.initials: LD
authors.lastname: Prisciandaro
authors.forename: Jane K
authors.initials: JK
authors.lastname: Fauser
authors.forename: Roger
authors.initials: R
authors.lastname: Yazbeck
authors.forename: Andrew
authors.initials: A
authors.lastname: Lawrence
authors.forename: Ker Y
authors.initials: KY
authors.lastname: Cheah
authors.forename: Tessa H
authors.initials: TH
authors.lastname: Wright
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Lymn
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Howarth
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D007583:Jejunum / Q000187:drug effects; D052016:Mucositis / Q000139:chemically induced* / Q000188:drug therapy*; D009195:Peroxidase / Q000378:metabolism; D019936:Probiotics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D048249:Streptococcus thermophilus; D013393:Sucrase / Q000187:drug effects / Q000378:metabolism
chemical_list: D009195:Peroxidase; D013393:Sucrase; D005472:Fluorouracil