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

William Crowe; Xiaobei Pan; James Mackle; Adam Harris; Gary Hardiman; Christopher T Elliott; Brian D Green

doi:10.1038/s41538-022-00174-y

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

NPJ Sci Food. 2022 Dec 28;6(1):60. doi: 10.1038/s41538-022-00174-y.

Authors

William Crowe¹, Xiaobei Pan¹, James Mackle¹, Adam Harris¹, Gary Hardiman¹, Christopher T Elliott^{1

2}, Brian D Green³

Affiliations

¹ Institute for Global Food Security, School of Biological Sciences, Queens University Belfast, Biological Sciences Building, Chlorine Gardens, Belfast, Northern Ireland, BT9 5DL, UK.
² School of Food Science and Technology, Faculty of Science and Technology, Thammasat University, 99 Mhu 18, Pahonyothin Road, Khong Luang, Pathum Thani, 12120, Thailand.
³ Institute for Global Food Security, School of Biological Sciences, Queens University Belfast, Biological Sciences Building, Chlorine Gardens, Belfast, Northern Ireland, BT9 5DL, UK. b.green@qub.ac.uk.

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 APC^Min mice to a greater extent than nitrite-free sausages, and this is associated with greater lipid peroxidation, wide-ranging metabolic alternation and gut dysbiosis.