Influence of A1 and A2 β-casein on early gut microbiota in a bovine animal model

Introduction: Bovine β-casein has two main variants associated with an amino acid change at residue 67, i.e., variants A1 and A2. The first variant has been associated with gastrointestinal discomfort and allergic problems due to the release of β-casomorphin-7 during protein digestion. The A2 variant may facilitate digestion and help prevent the gastric discomfort that some people experience when consuming milk. This work aims to determine whether A2 milk consumption has a positive effect on the growth and intestinal microbiota of newborn Holstein calves, used as an animal model.

Methods: Pregnant cows from a dairy farm were genotyped for A1 and A2 β-casein variants. Three cows homozygous for each of the genotypes (A1 or A2) were selected. Newborn male calves (n=6) were fed exclusively with maternal milk from their own mother, containing exclusively A1 or A2 β-casein. Calves were weighed at birth and weekly for two months. Stool samples were collected for microbiota analysis. Microbial DNA was extracted using the MagMax Microbiome Ultra Nucleic Acid Isolation kit and the V3-V4 region of 16s rRNA was sequenced with an Illumina Novaseq SP (PE250) equipment.

Results: The percentage of body weight gain two months after birth was higher in A2-fed calves (52.2 ± 10.1 %) than in the A1 group (47.6 ± 6.0 %), although this difference was not statistically significant. The relative abundance of Enterobacteriaceae and Eggerthellaceae was significantly higher in calves fed A1 milk compared to those fed A2 milk. On the other hand, the relative abundance of Erysipelatoclostridiaceae and Clostridia UCG-014 was higher in calves fed with A2 milk.

Conclusion: The type of beta-casein ingested shows an influence on growth and induces significant changes in the intestinal microbiota of calves, which may result inchanges in their intestinal health. More studies are necessary to confirm these changes and translate their possible effects to human health.