Dietary inclusion of nitrite-containing frankfurter exacerbates colorectal cancer pathology and alters metabolism in APCmin mice

Abstract

Colorectal cancer (CRC) is the second most prevelant malignancy in Europe and diet is an important modifiable risk factor. Processed meat consumption, including meats with preservative salts such as sodium nitrite, have been implicated in CRC pathogenesis. This study investigated how the CRC pathology and metabolic status of adenomatous polyposis coli (APC) multiple intestinal neoplasia (min) mice was perturbed following 8 weeks of pork meat consumption. Dietary inclusions (15%) of either nitrite-free pork, nitrite-free sausage, or nitrite-containing sausage (frankfurter) were compared against a parallel control group (100% chow). Comprehensive studies investigated: gastrointestinal tract histology (tumours), aberrant crypt foci (ACF), mucin deplin foci (MDF), lipid peroxidation (urine and serum), faecal microbiota, and serum metabolomics (599 metabolites). After 8 weeks mice consuming the frankfurter diet had 53% more (P = 0.014) gastrointestinal tumours than control, although ACF and MDF did not differ. Urine and serum lipid peroxidation markers were 59% (P = 0.001) and 108% (P = 0.001) higher, respectively in the frankfurter group. Gut dysbiosis was evident in these mice with comparably fewer Bacteriodes and more Firmicutes. Fasting serum levels of trimethylamine N-oxide (TMAO) and numerous triglycerides were elevated. Various serum phosphotidylcholine species were decreased. These results demonstrate that nitrite-containing sausages may exaccerbate the development of CRC pathology in APCMin mice to a greater extent than nitrite-free sausages, and this is associated with greater lipid peroxidation, wide-ranging metabolic alternation and gut dysbiosis.

Reduction, removal or replacement of sodium nitrite in a model of cured and cooked meat: a joint evaluation of consequences on microbiological issues in food safety, colon ecosystem and colorectal carcinogenesis

“…[39] MDF are proposed as cancer precursors and usable endpoints in short term carcinogenesis study with a good predictive character for tumor stage effects. [26] In this way, the very recent results of Crowe et al [40] confirmed our previous results at the tumor stage, by demonstrating also in Min mice that a nitrite-free sausage protects against promotion of intestinal tumors in comparison to nitrited ones. The results of our team, including the present study, and the results of Crowe et al support the role of nitrite salt food additive in colorectal cancer promotion associated to processed meat consumption.…”

Effects of sodium nitrite reduction, removal or replacement on cured and cooked meat for microbiological growth, food safety, colon ecosystem, and colorectal carcinogenesis in Fischer 344 rats

“…MDF are proposed as cancer precursors and usable endpoints in short term carcinogenesis study with a good predictive character for tumor stage effects 21 . In this way, the very recent results of Crowe et al 23 . confirmed our previous results at the tumor stage, by demonstrating also in Min mice that a nitrite-free sausage protects against promotion of intestinal tumors in comparison to nitrited ones.…”

Prevalence, types, and risk factors of functional gastrointestinal diseases in Hainan Province, China

“…This relationship between pickled foods and FGIDs has been rarely studied in previous research. Pickled foods are known to contain high levels of nitrite, and it has been observed that mice ingesting nitrite were more prone to developing intestinal flora disorders compared to those not ingesting nitrite 39 . This suggests that the pathogenesis of FGIDs caused by pickled foods may involve the disruption of intestinal flora, although further research is needed to confirm this hypothesis.…”