## 3 Results
### How Does A1 \(\beta\)-Casein Influence Immune Function? Casein, which makes up about 80% of the protein content in cow's milk [25; 35], has a complex interaction with the immune system. Research suggests that both casein itself and the peptides produced during its digestion may affect immune function in various ways. Casein is thought to generally support immune function by enhancing the immune system. Casein-derived peptides have been shown to strengthen immune responses, induce the death of malignant cells, and play a role in developing the mucosal immune system. Additionally, casein has been found to prevent colon cancer induced by azoxymethane in rats. There is also evidence pointing to the involvement of \(\alpha\)-casein in cancer suppression [66]. However, the digestion of A1 \(\beta\)-casein can release \(\beta\)CM-7, a bioactive peptide that can affect immune function and potentially contribute to the onset of allergies. \(\beta\)CM-7 has an affinity for opioid receptors and can influence inflammation and immune responses [22; 39]. Animal studies suggest that A1-like \(\beta\)-casein variants (A1/A1 and A1/A2) may trigger inflammatory reactions in the gastrointestinal tract by activating the Th2 pathway [13], as demonstrated by increased inflammatory markers and greater leukocyte infiltration. These effects are believed to be driven by both \(\beta\)CM-7 and BCM-5 [14]. Such inflammatory responses have also been linked to intolerance reactions like asthma and eczema [67]. SCFAs, known for their anti-inflammatory effects and their role in supporting colon cell function [68], have been found at lower levels in individuals who drink milk containing both A1 and A2 \(\beta\)-casein compared to those who consume milk with only the A2 variant. The exclusive consumption of A2 \(\beta\)-casein supports the production of microbial SCFAs, helping to prevent colonic health issues linked to insufficient SCFA production [33]. \(\beta\)CM-7 has a high affinity for \(\mu\)-opioid receptors, present not only in the nervous system but also in immune cells. By binding to these receptors, \(\beta\)CM-7 can modulate the activity of these immune cells. In vitro studies have shown that \(\beta\)CM-7 can alter lymphocyte proliferation and the release of inflammatory markers. The consumption of bovine milk containing \(\beta\)CM-7 can induce an inflammatory response in the gut by activating the Th2 pathway, which is central to the development of allergic responses, including IgE production [33]. [PERSON] et al. suggest that it may contribute to the etiology of food allergies [22]. In fact, a subcutaneous injection of \(\beta\)CM-7 can cause local pseudoallergic reactions, with when formation and erythema, mast cell degranulation, and histamine secretion even in healthy children, suggesting the allergenic potential of casein-derived peptides [69]. The study by [PERSON] et al. investigated the effects of the long-term (two-week) consumption of milk containing A1 and A2 \(\beta\)-casein (A1/A2) compared to milk containing only A2 \(\beta\)-casein in individuals with lactose maldigestion. A key finding was that while reductions in some gastrointestinal symptoms were observed with A2 milk over time, most serum immunological and antioxidant markers did not show significant differences between the two types of milk. The specific markers evaluated were IgG1,hs-CRP, and GSH. The exception was total IgG, which did show a difference between groups [50]. The lack of significant differences in these markers could suggest that, in the studied population of lactose intolerants over a two-week period, the type of \(\beta\)-casein did not induce noticeable systemic changes in these aspects of immunity. However, it could suggest that the type of \(\beta\)-casein could be affecting other IgG subclasses, resulting in a difference in total IgG without significantly affecting IgG1. The observed difference in total IgG requires further investigation to understand its significance.