Beneficial Effect of Consuming Milk Containing Only A2 Beta-Casein on Gut Microbiota: A Single-Center, Randomized, Double-Blind, Cross-Over Study.

Background/Aims Cow milk contains essential nutrients, with β-casein being a major protein that exists in both A1 and A2 forms. Recent studies suggest that A2 milk, which contains only A2 β-casein, may provide gastrointestinal (GI) benefits compared to regular milk that contains both A1 and A2 forms. This study investigated the impact of A2 milk consumption on the gut microbiota of a South Korean cohort experiencing GI discomfort after consuming A1/A2 milk. Methods The study included 35 participants who reported GI discomfort after consuming milk. High-throughput 16S ribosomal RNA metagenomics sequencing was performed on stool DNA before and after consumption of either A1/A2 or A2 milk. Results The study found that consuming A2 milk significantly altered gut microbiota composition, as evidenced by a notable shift in beta diversity, while no such change was observed after consuming A1/A2 milk. There were significant differences in gut microbiota between the A1/A2 and A2 milk groups. While alpha diversity indices showed no substantial changes, taxonomic analysis revealed a significant increase in beneficial bacteria such as Bifidobacterium and Blautia after A2 milk consumption (Figure 1). LEfSe analysis highlighted the enrichment of Actinobacteria, including Bifidobacterium longum and Blautia wexlerae, and PICRUSt analysis showed enhanced transport systems related energy- coupling factors and various sugars in the A2 milk group. Spearman correlation analysis demonstrated a significant correlation between Bifidobacterium, Blautia, and enhanced transport systems, observed only in the A2 milk consumption group. Conclusion The study concluded that consuming A2 milk for two weeks led to significant alterations in gut microbiota composition, promoting an increase in beneficial microbes and their associated functions. A2 milk may be a beneficial dietary alternative in terms of its impact on gut microbiota. (ClinicalTrials.gov Registration Numbers NCT06252636 and CRIS KCT0009301). [ABSTRACT FROM AUTHOR]