Comparative Analysis of the Effects of UNICLA-A2 Against Conventional Dairy Products Administered Daily in Patients at High-risk Colorectal Cancer Development Who Have Undergone Polypectomy

Colorectal cancer (CRC) is one of the most frequent cancers in the world and has a significant impact in terms of mortality and health costs. It is estimated that CRC causes around 900,000 deaths annually, mainly due to diagnoses made in advanced stages. Colorectal adenomas (CRA) are precancerous lesions that develop into colorectal cancer following a well-known process into the adenoma-carcinoma sequence. Prevention programs include screening for CRA and removing precancerous lesions by polypectomy, but the high recurrence rates after polypectomy makes it necessary to research on potential chemopreventive agents that may reduce this risk. Dietary recommendations or chemoprevention with different nutritional substances (diets rich in fiber, or poor in red meat, etc) or pharmacological substances including vitamin D, calcium, fatty acids, salicylic acetyl acid, nonsteroidal anti-inflammatory agents (NSAIDs), etc) have been studied. In this way, it seems reasonable to evaluate the effect caused by the administration of certain nutrients that affect lipid and protein metabolism involved in cellular homeostasis, in the preservation of the colonic mucosa or the development of lesions may have in populations at risk.

UNICLA A2 dairy products have a different nutrient profile than conventional ones. UNICLA A2 products have higher content in unsaturated fats, that is to say, increased content of healthy fatty acids such as oleic, linolenic, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and conjugated linoleic acid (CLA). Previous studies have suggested a contribution of ω-3 polyunsaturated fatty acids (PUFAs) to reduce pro-inflammatory markers and, have shown they have antimicrobial and negative properties in relation to biofilm formation. These types of biofilm structures are characteristic of proximal CRC. For these reason, ω-3 PUFAs it is thought that they could modify the altered intestinal microbiota in patients at high risk of CRC towards a less pathogenic environment, correcting the gut dysbiosis. Moreover, they have higher selenium levels (Se), an element with essential biological functions which has been suggested improving effects in combination with other anticancer agents in CRC and taking part in the modulation of several processes, such as the immune response, apoptotic cell death, DNA repair, response to oxidative stress, carcinogenic metabolism, tumorigenesis and angiogenesis. Finally, they contain type A2 beta casein, which differs from A1 beta casein by a single amino acid at position 67 of a 107 amino acid chain. This fact is very important because beta casein contains a chain of amino acids called "beta casomorphin" (BCM7) with negative health effects reported. The proline 67 in beta casein A2 has a strong bond with BCM7 that does not allow it to separate and flow freely in milk to be absorbed. However, the mild bond due to histidine 67 in beta casein A1 allows BCM7 to reach the intestinal wall and be absorbed, being associated with intestinal discomfort, gastrointestinal transit time and stool consistency disturbances, abdominal pain and, increased levels of some inflammatory markers.

For these reasons, in this proposal the investigators aim to determine whether the change from conventional dairy products to UNICLA-A2 products but maintaining the habitual consumption habits in "real life" conditions, without forcing or inducing greater consumption, will have positive effects on maintaining the intestinal integrity by reducing the inflammatory profile, and leading the gut microbiota to a less pathogenic environment in patients at high-risk of CRC development.