Fecal Water Genotoxicity Is Predictive of Tumor-Preventive Activities by Inulin-Like Oligofructoses, Probiotics (Lactobacillus rhamnosus and Bifidobacterium lactis), and Their Synbiotic Combination

Abstract

Abstract: The measurement of fecal water genotoxicity in human colon cells could be a useful biomarker to study effects of diet in the colon. Here we assessed aqueous fecal extracts of samples from a chronic study with rats fed prebiotics, probiotics, and their combination. Treatments were maltodextrins (controls), inulin/oligofructoses (prebiotic), Lactobacillus rhamnosus, and Bifidobacterium lactis (probiotics) or both (synbiotic). Azoxymethane (AOM) was administered to initiate tumors. Rat feces were collected at 0 and 10 days and 2, 4, and 8 mo, and cecal contents were collected at 8 mo. Aqueous phases were prepared and tested for genotoxicity in HT29 colon cells using the comet assay. The studied types of intervention reduced fecal and cecal genotoxicity. DNA damage by samples from AOM-treated, tumor-free rats was significantly lower than from tumor-bearing animals, especially after 4 mo of synbiotic and prebiotic interventions. Inulin-based diets reduced exposure to genotoxins in the feces, directly reflecting the reported reduction of tumor incidence in these animals. Evidence is provided for the validity of this measurement as a biomarker of chemoprevention because 1) fecal water genotoxicity reflected genotoxic exposure in the cecum, 2) tumor incidence and fecal genotoxicity were directly related, and 3) these interventions reduced tumor risks by reducing exposure to genotoxins in the gut.