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

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.

Variability in fecal water genotoxicity, determined using the Comet assay, is independent of endogenous N‐Nitroso compound formation attributed to red meat consumption

“…The fecal water fraction of human feces is routinely used when studying the link between diet and colorectal cancer using the Comet assay [Burns and Rowland, 2004;Klinder et al, 2004;Glei et al, 2005] because of the particulate nature of fecal homogenates, which interferes with the Comet, and other assays. Previous findings have shown that cytolytic agents are usually capable of exerting their effects only when in solution and that dietary changes may alter the composition of fecal water fractions [Rafter et al, 1987;Lapre and Van der Meer, 1992].…”

“…Moreover, the fecal water fraction is more efficient in altering the growth characteristics of colonocytes than components of the solid phase [Rafter and Branting, 1991;Lapre and Van der Meer, 1992]. Recently, Klinder et al [2004] demonstrated a close association of fecal water genotoxicity and tumor risks in a rat study.…”

The bifidogenic effect of inulin and oligofructose and its consequences for gut health

“…In addition, there is a wide range of measurement techniques to monitor other markers of gut health, such as the measurement of changes in metabolite profile (SCFA, lactate;de Graaf and Venema, 2008), several parameters of colonization resistance against pathogens and the integrity of the intestinal lining or immunomodulation Albers et al, 2005). In addition, a battery of intermediate biomarkers for colon cancer is available, including the activity of certain faecal enzymes and the modulation of genotoxicity of faecal water (Klinder et al, 2004;Rafter et al, 2007). The scheme in Figure 3 represents the cascade of physiological effects that can be induced by consumption of either inulin-type fructans or probiotic bacteria or a combination of both, the so-called synbiotics.…”

Importance of Probiotics in Gastrointestinal Tract

“…In a variety of animals models involving rats and mice which were fed on oligofructose and/or insulin reduce the fecal water genotoxicity [97]. The numbers of precancerous lesions which are induced chemically are decreased [98,99] and also defense function is stimulated.…”