Harini Pennathur

Background: Colorectal cancer (CRC) is the third leading cause of cancer-related mortalities in the US¹. Alarmingly, incidence is rising in young people (age < 50) in a condition termed as Early Onset CRC (EOCRC)². Systematic review shows a 30% rise in EOCRC around the world, primarily driven by rising incidence in the United States, Canada, and Australia. While 30% of EOCRC cases are due to hereditary/family history cancer, most cases arise sporadically. Recent studies have turned to understanding preventative and protective mechanisms such as diet, and its impact on the gut microbiome as promising insight into the cause for generational shift and to develop preventative strategies.

Methods: A database search through PubMed was conducted using a combination of the following MeSH search terms: “colorectal cancer”, “colon cancer”, “rectal cancer”, “colorectal adenomas”, “microbiome”, “diet”, “high-fat diet”, and “dietary fiber”. Exclusion criteria included studies published more than five years prior to search date.

Results: In 2021, a study was conducted in which two sets of mice were randomized to one of two interventions: a high fat diet (HFD) or a control diet (CD)³. Results showed that HFD mice had larger and more numerous colonic adenoma and tumor development when compared with CD mice. In the same study, a stool transfer from the HFD to CD mice showed increased dysplasia and disorganization in colonic wall structure. Moreover, expression of tight junction proteins E-cadherin and Claudin-3 (both markers of gut barrier integrity) were significantly reduced in HFD mice. Other studies showed that there are several gut microbiome constituents that are increased in patients with CRC including Alistipes, Akkermansia spp., Fusobacteria, Porphyromondaceae, Coribacteridae, and Methanobacterials⁴. In HFD mice, Alistipes was significantly increased³. A proposed mechanism for the dysbiosis of the gut by HFD is through an increased acid load⁵. In case-controlled study examining this relationship, researchers found that high fat foods (red meats, poultry, eggs, protein, etc.) were positively associated with diet-dependent acid load. Conversely, plant-based foods (legumes, fruits, and vegetables) were negatively associated with diet-dependent acid load. Further, increased diet-dependent acid loads were significantly correlated with an increase in CRC and colorectal adenoma (CRA) formation.

Conclusion: Diet and its effect on the gut microbiome proves to be a prominent modulator of CRC tumorigenesis and gut wall integrity. Rebuilding and preserving the gut microbiota can serve as a powerful tool in the reduction of CRC risk and incidence.

Works Cited

1. Harris KL, Harris KJ, Banks LD, Adunyah SE, Ramesh A. Acceleration of benzo(a)pyrene-induced colon carcinogenesis by Western diet in a rat model of colon cancer. Curr Res Toxicol. 2024;6:100162. Published 2024 Mar 7. doi:10.1016/j.crtox.2024.100162
2. Wu CW, Lui RN. Early-onset colorectal cancer: Current insights and future directions. World J Gastrointest Oncol. 2022;14(1):230-241. doi:10.4251/wjgo.v14.i1.230
3. Yang J, Wei H, Zhou Y, et al. High-Fat Diet Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites. Gastroenterology. 2022;162(1):135-149.e2. doi:10.1053/j.gastro.2021.08.041
4. Siddiqui R, Boghossian A, Alharbi AM, Alfahemi H, Khan NA. The Pivotal Role of the Gut Microbiome in Colorectal Cancer. Biology (Basel). 2022;11(11):1642. Published 2022 Nov 9. doi:10.3390/biology11111642
5. Jafari Nasab S, Rafiee P, Bahrami A, et al. Diet-dependent acid load and the risk of colorectal cancer and adenoma: a case-control study. Public Health Nutr. 2021;24(14):4474-4481. doi:10.1017/S1368980020003420