## 4 Conclusions  
The interaction between \(\beta\)CM-7, a bioactive peptide released during the digestion of A1 \(\beta\)-casein, and the gut microbiota has significant implications for gut health and overall well-being. Studies suggest that milk containing A1 \(\beta\)-casein may negatively impact gut health by altering microbiota composition, reducing motility, and increasing fermentation in the colon. These effects are linked to the increased production of gases like hydrogen and changes in short-chain fatty-acid (SCFA) profiles. Conversely, milk containing only A2 \(\beta\)-casein has been associated with improved gastrointestinal outcomes, including an increased abundance of beneficial bacteria like _Bifidobacterium_ spp. and reduced markers of inflammation.  
Research indicates that \(\beta\)CM-7 can compromise intestinal barrier function by increasing permeability and triggering inflammatory responses. This may exacerbate gastrointestinal symptoms in individuals with lactose intolerance, irritable bowel syndrome (IBS), or other sensitivities. Furthermore, \(\beta\)CM-7's ability to cross the blood-brain barrier and interact with \(\mu\)-opioid receptors in the central nervous system highlights its potential neurological effects.  
Individual responses to \(\beta\)CM-7 vary due to factors such as enzyme activity (e.g., DPP-4), genetic predisposition, gut microbiota composition, and intestinal permeability. For example, individuals with lower DPP-4 activity may experience higher circulating levels of \(\beta\)CM-7 after consuming A1 \(\beta\)-casein, intensifying its effects. Elevated levels of \(\beta\)CM-7 have been observed in populations with specific conditions, such as ASD, suggesting a potential role in these groups.  
Clinical studies (30 of which 24 were interventional clinical trials, 3 epidemiological studies, and 3 non-interventional studies, including 12 studies with children and/or adolescents and multiple trials with adults) have consistently shown that milk containing only A2 \(\beta\)-casein is better tolerated than milk with both A1 and A2 \(\beta\)-caseins. Participants consuming A2 milk reported fewer gastrointestinal symptoms such as bloating, abdominal pain, and fecal urgency. Additionally, inflammatory biomarkers were lower in those consuming A2 milk compared to conventional milk.  
In conclusion, the evidence underscores the distinct effects of A1 and A2 \(\beta\)-caseins on gut health. While A1 \(\beta\)-casein is associated with adverse gastrointestinal outcomes and inflammation, A2 \(\beta\)-casein offers a more favorable profile for individuals sensitive to dairy products. However, further research is needed to explore these effects across diverse populations and clinical settings to fully understand their implications for human health.  
Conceptualization, C.F. formal analysis, C.F., A.L. and P.R.; investigation, C.F., A.L., P.R. and N.G.-R.; resources, C.F., A.L., P.R. and N.G.-R.; data curation, C.F., A.L., P.R., N.G.-R., N.V.-L. and A.R.-S.; writing--original draft preparation, C.F., A.L., P.R., N.G.-R. and N.V.-L.  
writing--review and editing, C.F., A.L., P.R., N.G.-R., N.V.-L. and A.R.-S.; visualization, C.F., A.L., P.R., N.G.-R., N.V.-L. and A.R.-S.; supervision, C.F., A.L. and P.R. All authors have read and agreed to the published version of the manuscript.  
This research received no external funding.  
Not applicable.  
During the preparation of this manuscript, the authors used DeepL Translate for the purpose of correcting minor grammatical errors. The authors have reviewed and edited the output and take full responsibility for the content of this publication.  
The authors declare no conflicts of interest.