Colorectal cancer (CRC) is thought to be strongly associated with environmental exposures including diet. Components ingested through the diet are a major source for exposure of the colonic epithelium to mutagenic compounds that may cause both initiation of cell transformation and tumor progression [1, 2]. The objective of the current study was to determine if dietary habits, previously shown to differ between African Americans (AA) and Caucasian Americans (CA), effect the composition of gut microbiota and result in differences in fecal water cytotoxicity/genotoxicity.
AA suffer from an increased incidence and mortality of CRC in comparison to CA (American Cancer Society: Statistics for 2008, http://www.cancer.org/docroot/stt/stt_0.asp?from=fast). Although the underlying causes for these differences are not well established it is plausible that differences in dietary habits in AA affect the colonic environment by increasing exposure to mutagens directly as well as indirectly through changes in the composition of the metabolically active gut microbiota . In a previous large study of associations between diet and CRC in AA and CA in North Carolina differences between the two racial groups were detected in the intake of micro- as well as macronutrients [4–6]. This study also suggested that associations between diet and CRC might differ between the two racial groups. One observation in the above study was an increased intake of heterocyclic amines (HCAs) by AA. HCAs such as 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and also benzo[a]pyrene (Bap) a polycyclic aromatic hydrocarbon (PAH), are possible humancarcinogens formed during meat cooking. Large amounts of HCA are formed with longer cooking times, internal temperatures of between 150°C and 200°C, and greater external charring , typically achieved with cooking methods such as barbeque.
Humans harbor in their guts a complex intestinal microbiota that varies in its composition between individuals. Although recent studies have shed some light on the complexity of the gut microbiota in a limited number of individuals, the extent of microbiota diversity and associations with dietary habits are still poorly understood . Tremendous advances in our understanding of the composition and activities of the gut microbiota have recently been made, however, we still do not fully understand the degree of complexity or the dynamics of the human gut microbiota [9, 10]. It is now well established that the human gut microbiota is phylogenetically as well as metabolically very diverse and makes important contributions to the physiology of its human host [11, 12]. Eloquent studies have shown communication between gut microbiota and the human host, a requirement of gut microbiota for appropriate priming and development of the immune system and associations between gut microbiota and obesity mediated by the induction/suppression of various human factors [13–17]. The host microbiota can have profound effects on nutrient acquisition and sequestering, immune priming and reactivity, as well as direct effects on carbohydrate and other compound levels in the systemic circulation [18, 19]. The microbiota has long been suspected to be associated with health as well as with diseases including inflammatory bowel diseases and CRC, recent data supports an association between reduced microbiota diversity and Crohn's disease .
Fecal water, the water-soluble fraction obtained as the supernatant after high speed centrifugation of total feces, reflects the luminal content of both risk factors and protective factors . Cytotoxicity/genotoxicity of fecal water is a useful biomarker in studying the impact of environmental factors on exposure of the gut to carcinogens and the modification of this exposure by dietary habits [22–24]. Cytotoxicity/genotoxicity of fecal water can be assessed in vitro by exposing cultured human colon cells, followed by assessment of cell viability and DNA damage in single cells by the Comet assay . Fecal water genotoxicity has previously been shown to be related to colon carcinogenesis in animals . In human studies, fecal water genotoxicity was higher after a diet rich in meat as compared to a diet enriched in fiber . Supplementation with probiotic yoghurts has been shown to reduce fecal water genotoxicity . There also appears to be an effect modification by smoking status as supplementation with bread enriched with prebiotics and antioxidants reduced the fecal water genotoxicity in non-smokers but not in smokers, an effect which differed by the status of GST M-polymorphisms .
In this study we investigated if differences in dietary habits between the two groups are associated with cytotoxicity/genotoxicity of fecal water and with fecal microbiota composition.