## 3 Results
### How Do \(\beta\)CM-7 and the Microbiota Interact in Gut Health and Disease Regulation?
Gastrointestinal symptoms caused by the consumption of conventional milk are accompanied by higher concentrations of inflammatory biomarkers such as fecal calprotectin and lower total fecal short-chain fatty acids [28], alterations in cysteine availability and glutathione synthesis [39], and the induction of oxidative stress [39; 62]. [PERSON] et al. suggest that A2 milk could be an alternative for athletes who are intolerant to A1 protein, implying that some athletes may experience digestive problems with regular milk due to the presence of A1 \(\beta\)-casein [44]. In summary, the evidence suggests that \(\beta\)-casein A1 may contribute to a higher incidence of adverse gastrointestinal symptoms and inflammation compared to A2 \(\beta\)-casein in children and adults, especially those with milk or lactose intolerance. Milk containing only A2 \(\beta\)-casein is often associated with better gastrointestinal tolerance. However, further research in different populations and settings is needed to fully confirm and understand these effects. Is There an Association Between A1 \(\beta\)-Casein Consumption and an Increased Risk of Cardiovascular Disease? Human trials evaluating the relationship between A1 \(\beta\)-casein consumption and cardiovascular disease have yielded mixed results. On the one hand, [PERSON] et al. [26] analyze diverse biochemical and diagnostic markers associated with cardiovascular disease. To assess cardio protection, various parameters have been studied, including endothelial function (related to nitric oxide bioavailability, an early marker of atherosclerosis), arterial function (vascular biomechanics), resting blood pressure, plasma lipids, and biochemical markers of inflammation. Endothelial function is a key predictor of future cardiovascular events, while increased arterial stiffness has been associated with decreased survival in hypertensive patients [65]. Plasma markers associated with cardiovascular disease (CVD) include hyperinsulinemia, hypernocrysteinemia, and C-reactive protein (CRP). The study concluded that no cardiovascular disadvantages were found associated with the consumption of A1 casein compared to A2 casein. However, this review found that several human trials suggest a possible relationship between A1 \(\beta\)-casein consumption and increased inflammation in adults through the study of biomarkers as IL-4, myeloperoxidase, monocyte chemoattractant protein-1, IgE, IgG, IgG1, IgG2a, Toll-like receptors 1 and 2, TNF-\(\alpha\), cortisol, LBP, CD14, fecal calprotectin, and hs-CRP. Additionally, glutathione has been analyzed as a marker of redox balance. [PERSON] et al. observed that the consumption of conventional milk containing A1 and A2 \(\beta\)-casein increased the serum levels of IL-4 and other inflammatory markers [33]. [PERSON] et al. measured fecal calprotectin, finding an increase in its levels after exposure to A1 \(\beta\)-casein [28]. [PERSON] et al. addressed the redox homeostasis of thiols in the context of neurodegenerative diseases, highlighting the role of glutathione. The study showed that the consumption of milk containing only A2 \(\beta\)-casein was associated with a greater increase in plasma glutathione concentrations compared to the consumption of milk containing both types of \(\beta\)-casein (A1 and A2) [39]. Lower levels in A1 \(\beta\)-casein are due to a limitation in the cellular uptake of cysteine, which is a limiting precursor for GSH synthesis. Oxidative stress and inflammation are relevant processes in the pathogenesis of cardiovascular disease, and glutathione plays a role in modulating these processes, so an indirect relationship can be inferred. A1 casein-induced glutathione reduction could contribute to increased oxidative stress and inflammation, which in turn could have implications for the development of cardiovascular disease. Glutathione plays a role in protecting nitric oxide (NO) bioavailability by reducing oxidative stress.