Consumption of Select Dietary Emulsifiers Exacerbates the Development of Spontaneous Intestinal Adenoma

Abstract

Inflammation is a well-characterized critical driver of gastrointestinal cancers. Previous findings have shown that intestinal low-grade inflammation can be promoted by the consumption of select dietary emulsifiers, ubiquitous component of processed foods which alter the composition and function of the gut microbiota. Using a model of colitis-associated cancer, we previously reported that consumption of the dietary emulsifiers carboxymethylcellulose or polysorbate-80 exacerbated colonic tumor development. Here, we investigate the impact of dietary emulsifiers consumption on cancer initiation and progression in a genetical model of intestinal adenomas. In APCmin mice, we observed that dietary emulsifiers consumption enhanced small-intestine tumor development in a way that appeared to be independent of chronic intestinal inflammation but rather associated with emulsifiers’ impact on the proliferative status of the intestinal epithelium as well as on intestinal microbiota composition in both male and female mice. Overall, our findings further support the hypothesis that emulsifier consumption may be a new modifiable risk factor for colorectal cancer (CRC) and that alterations in host–microbiota interactions can favor gastrointestinal carcinogenesis in individuals with a genetical predisposition to such disorders.

The Role of Diet and Lifestyle in Early-Onset Colorectal Cancer: A Systematic Review

“…Carboxymethylcellulose (CMC) and polysorbate 80 (P80) are some of the most commonly used emulsifiers, a subtype of food additives. Their regular consumption showed to exacerbate colorectal tumor development in a preclinical model of colitis-induced colorectal cancer [ 215 ], and to aggravate the initiation and development of genetically driven CRC, as demonstrated in mice mutated for the tumor suppressor gene APC [ 216 ]. In this study, the LINE-1 methylation status on formalin-fixed, paraffin-embedded samples of neoplastic colonic mucosa as well as microbiota on stool samples of eoCRC patients could be evaluated in relation to dietary and lifestyle habits, also taking into account the new “age continuum” model proposed by Akimoto et al for this epigenetic alteration as compared to the sharp distinction between eoCRC and loCRC with the age cut-off set at 50 years [ 138 ].…”

Opinion on the re‐evaluation of sodium carboxy methyl cellulose (E 466) as a food additive in foods for infants below 16 weeks of age and follow‐up of its re‐evaluation as food additive for uses in foods for all population groups

“…APC min mice – which are predisposed to intestinal adenoma formation – showed an increased number of adenomas in the small intestine, but not in the colon when fed a diet containing carboxy methyl cellulose (Viennois and Chassaing, 2021 ). Mutations in the APC gene are known to lead to adenomas and later, carcinomas, in the colon in humans (Markowitz and Bertagnolli, 2009 ).…”

“…The Panel was made aware of recent studies in which sodium carboxy methyl cellulose was investigated in mice and humans. These studies addressing the microbiota and a few toxicological endpoints showed changes in the microbiota composition in mice and also in humans (Arnold et al, 2022;Chassaing et al, 2022;Chassaing et al, 2015;Naimi et al, 2021;Sandall et al, 2020;Viennois et al, 2020;Viennois and Chassaing, 2021). However, the consequences and the meaning of these changes in the microbiota composition for relevant health outcomes are currently not clear.…”

Emerging Evidence on the Effects of Dietary Factors on the Gut Microbiome in Colorectal Cancer

“…This along with unhealthy dietary habits, obesity, heme iron, and associated alterations in gut microbiota enhance oncogenic changes in colonic mucosa ( 68 ). Viennois et al reported that consumption of dietary emulsifiers such as carboxymethylcellulose (CMC) and polysorbate 80 (P80) alter the composition of the gut microbiome and increase the risk for intestinal inflammation and adenoma formation in Apc min mice ( 69 ). Emulsifier consumption lowered the abundance of Clostridia (in both male and female mice) and increased the abundance of Proteobacteria (in male mice).…”

“…Emulsifier consumption lowered the abundance of Clostridia (in both male and female mice) and increased the abundance of Proteobacteria (in male mice). Proteobacteria has been putatively linked to altered gut microbiome and risk for cancer ( 69 , 70 ). In another study, Viennois et al reported that CMC and polysorbate 80 induce low grade inflammation and alteration in the gut microbiota such as increase in Bacteroidales and decrease in Clostridiales ( 53 ).…”