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) and 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.
Competing Interest Statement
W.C. X.P. G.H. J.M. A.H and B.D.G declare no competing interests. C.T.E. declares that he is an editor for npj Science of Food, but was not involved in the journal review of, or decisions related to this manuscript.
Footnotes
The manuscript has underwent peer-review and in responding to the reviewers the following changes have been incorporated: - Line numbers have been added throughout the text. - Clarification of the term 'Lachnospiraceae' has been given for this bacterial family - Figure 4C has been updated to more accurately reflect the % bacterial composition, and a Supplementary Table has now been included to provide details. - It has been acknowledged that other alternative mouse models exist such as humanised or colon-specific models which could be used in future studies. - Some additional references have been cited and older articles have been replaced with more recent articles - several typographical and grammatical errors have been corrected - A minor text change has been made to Figure 1A - Tables and Figure legends have been amended to explain whether figures show S.E.M or S.D.
