## 3 Results
### How Do \(\beta\)CM-7 and the Microbiota Interact in Gut Health and Disease Regulation? The gastrointestinal mucosa represents the interface between the internal and the external environment. It is composed of multiple layers with specific functions whose integrity is essential for the body's health and defense [55]. The gut microbiome, considered a \"hidden organ\", plays a fundamental role in metabolism and immunity, highlighting its importance in health and disease management. Diet is a determining factor in gut-microbiota regulation, providing nutrients that influence its population. The microbiota, in turn, impacts nutrient absorption, metabolism, and host physiology [56]. \(\beta\)CM-7 acts as an agonist of \(\mu\)-opioid receptors, which are predominantly found on nerve cells within the enteric nervous system that innervates the intestinal lining [57]. The activation of these receptors plays a vital role in numerous gastrointestinal functions, including maintaining the integrity of the intestinal barrier, regulating secretions, and  
\begin{table}
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**Reference** & **Study Design** & **Population** & **Methodology** & **Outcome** & **Results** & **Main Finding** \\ \hline ([PERSON] et al., 2017) [44] & RCT placebo-controlled & 21 athletes & Post-exercise milk intake & Muscle recovery & A2 and regular milk \(>\) placebo & A2 helps in recovery for A1-intolerant \\ \hline ([PERSON] A \& [PERSON] \(G\)X, 2017) [53] & RCT crossover & 40 adults + 30 preschool children & A1/A2 vs. A2 milk & Cognitive tests (D8 ST) & A2 improved processing speed & A2 enhances cognition and comfort \\ \hline ([PERSON] et al., 2019) [22] & Case-control & 137 children & \(\beta\)CM-7, DFPIV assays & Serum/urine levels & \(\dagger\)\(\beta\)CM-7 and DPPIV in ASD & Daily peptides may relate to ASD \\ \hline ([PERSON] et al., 2019) [54] & RCT crossover & 75 preschoolers & 5 days A1/A2 vs. A2 milk & GI symptoms, inflammation with A2 & A2 improves comfort and cognition \\ \hline ([PERSON] et al., 2020) [20] & RCT & 40 women & Milk challenge by type & Digestive symptoms & \(\Delta  
controlling motility [58]. Milk that contains both A1 and A2 \(\beta\)-casein may influence the gut microbiota differently than milk with only the A2 variant. Through its action, \(\beta\)CM-7 could indirectly impact the composition of the microbiota, thereby affecting gut motility, mucus secretion, and potentially contributing to inflammation [38]. Some research suggests that consuming only A2 \(\beta\)-casein may support better gastrointestinal function, possibly by promoting beneficial microbial populations. In contrast, A1 \(\beta\)-casein may be linked to slower digestion in the small intestine and increased fermentation in the colon, leading to changes in gas production and modifications in the microbial ecosystem [37]. For example, one study found that milk containing A2 \(\beta\)-casein can significantly boost the levels of _Bifidobacterium_, a bacterial genus known for its positive effects on gut health [52]. Additionally, other studies have indicated that the intake of milk with A1 \(\beta\)-casein is associated with alterations in the production of short-chain fatty acids--such as butyric, acetic, and propionic acids--which are important for colon health [33; 40; 43]. Regarding gut-barrier function, animal studies have shown that the consumption of A1 milk can trigger an inflammatory response characterized by increased myeloperoxidase (MPO) activity and increased neutrophil infiltration into the colon [17]. Furthermore, \(\beta\)CM-7 activates the TLR-2 and TLR-4 receptors, enhancing the immune response and potentially compromising the intestinal barrier function by increasing its permeability. Intestinal inflammation, which has been associated in some studies with the consumption of A1 \(\beta\)-casein, can disrupt the composition of the colonic microbiota and promote the growth of pathogens [28].