The comparative effects of milk containing A1/A2 β-casein vs milk containing A2 β-casein on gut and cardiometabolic health in humans

Consumption of A2 milk is often believed to have a wide range of health benefits, however clinical data regarding effects on gut inflammation, gastrointestinal symptoms and function, blood lipids, body composition, glucose metabolism and blood pressure is either conflicting or limited. There is also a lack of evidence on the prebiotic effect of bovine milk and on the effects on health of the bovine BCM-5 and 7 peptides released from A1 β-casein. The work described in this thesis combined an in vitro investigation comparing the effect of digested bovine milk containing A1/A2 with that containing only A2 β casein variants and their peptides on gut microbiota fermentation properties as well as a human intervention study comparing milk containing both A1 and A2 β casein variants with milk containing only the A2 β casein variant on gut inflammation and risk markers of cardiometabolic disease. In the in vitro studies, the milks were digested and then the digested milk and BCM-5 and 7 peptides were fermented in anaerobic pH-controlled faecal batch cultures and bacterial concentration and diversity and short chain fatty acids were analysed. In the human study, regular consumers of milk who experienced gastrointestinal symptoms after drinking milk not due to lactose participated in a double blind randomised crossover study for a 10 week period started and separated with 2 weeks washout. Commitment to the dietary regimes was achieved by specific dietary advice. In the in vitro fermentation study, BCM-7 was released only from milk containing both β casein variants A1/A2 during the enzymatic digestion and both digested milks altered bacterial diversity similar to FOS (prebiotic) and this was seen in the increase of total bacteria and bifidobacteria, while BCM peptides behaved similarly to negative control that did not contain any treatment. Both milks resulted in a greater increase than BCM peptides in SCFA propionate, butyrate and acetate. In the human study, milk with only A2 β casein significantly decreased C-reactive protein and increased Actinobacteria in faeces, stool frequency and haemoglobin relative to the A1/A2 milk. A2 milk had a tendency to lower bloating and abdominal cramps whilst A1/A2 milk significantly decreased serum high-density lipoprotein cholesterol (HDL-C), glucose, diastolic blood pressure (DBP) and heart rate. However, there were no effects on local gut inflammation, other blood lipids and body composition. This study demonstrates that milks behave similar to prebiotic in vitro and this could be influenced by the type of oligosaccharides that alter the microbiota composition. In addition, consumption of milk had no pro-inflammatory effects on the human gut, but A2 milk may improve or eliminate gastrointestinal symptoms associated with milk intolerance.