Oral ingestion of streptococcus thermophilus diminishes severity of small intestinal mucositis in methotrexate treated rats.
BACKGROUND
Currently, there are no available effective preventative or adjunctive agents to alleviate symptoms of chemotherapy-induced mucositis. This is compounded by the absence of a recognized and validated noninvasive biomarker to assess gut function. This study investigated the effects of orally ingested Streptococcus thermophilus (TH-4) on chemotherapy-induced small intestinal damage in rats using the noninvasive (13)C-sucrose breath test (SBT).


METHODS
Gastrointestinal damage was induced in 27 female dark agouti rats (148 +/- 1g) with MTX (1.5 mg/kg; i.m.). Rats received MTX or saline at 0 h; with daily treatment of: TH-4 at doses of 10(9) (high), 10(8) (low) cfu/mL, or skim milk (vehicle), 48 h pre and 96 h post-MTX. The noninvasive (13)C-sucrose breath test (SBT) was conducted at -24, 24 and 96 h post-MTX to monitor gut function. At sacrifice, small intestinal tissues were collected for determinations of sucrase activity, myeloperoxidase (MPO) activity and histological assessment.


RESULTS
MTX + vehicle and MTX + low TH-4-treated rats produced significantly lower SBT and sucrase activity results compared to saline controls (p < 0.001). In contrast, MTX + high TH-4 treatment showed no significant differences in the SBT compared to saline controls, and the SBT results were significantly higher compared to MTX + vehicle and MTX + low TH-4 (p < 0.05). MPO levels were significantly elevated (p < 0.05) in MTX + vehicle and MTX + low TH-4, but not following MTX + high TH-4 treatment, compared to saline controls. This was further confirmed by histological analyses.


CONCLUSIONS
Oral ingestion of TH-4 at 10(9) cfu/mL is capable of partially attenuating small bowel damage in rats. The noninvasive SBT is a useful technique to longitudinally assess the efficacy of treatments or interventions for small bowel disease.
Tooley
Katie L
KL
Centre for Paediatric and Adolescent Gastroenterology, Children, Youth and Women's Health Service, North Adelaide, South Australia.
Howarth
Gordon S
GS
Lymn
Kerry A
KA
Lawrence
Andrew
A
Butler
Ross N
RN
D000284:Administration, Oral; D000818:Animals; D004327:Drinking Behavior; D005247:Feeding Behavior; D005260:Female; D007421:Intestine, Small / Q000473:pathology*; D008727:Methotrexate / Q000633:toxicity*; D052016:Mucositis / Q000139:chemically induced / Q000382:microbiology / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D048249:Streptococcus thermophilus
D008727:Methotrexate