Early post-natal methionine supplementation in ewe lambs: Long-term effects on feed efficiency, milk yield and fatty acid profile, metabolism, gut microbiome, and epigenetic regulation

Nutritional strategies that supply methyl donors, such as methionine in the early post-natal period of lambs could program feed efficiency, milk production and metabolism along the whole life due to persistent changes in epigenetic marks. To test this hypothesis, 34 newborn ewe lambs from the same flock were stratified and distributed into two groups with equal body weight distribution. The control group (F0-CTRL, n = 17) was fed ad libitum with a milk replacer. In contrast, the second group (F0-MET, n = 17) received the same milk replacer supplemented with 1 g methionine/kg DM. After weaning, all animals were raised the same way and fed ad libitum with a complete pelleted diet formulated according to nutrient requirements. At 45 days of age, blood was collected from the jugular vein for DNA isolation, and DNA methylation was analyzed by Reduced Representation Bisulfite Sequencing (RRBS) in ten animals [5 ewe lambs (F0-MET) vs. 5 ewe lambs (F0-CTRL), corresponding to 5 twin births, of which one lamb was assigned to each group]. The main results show that CPT1B, a gene involved in fatty acid catabolism, was differentially methylated in F0-MET lambs (45 days of life). In addition, these animals presented increased insulin and non-esterified fatty acid concentrations while cholesterol levels were reduced, most of these changes being persistent along the whole life. No differences were observed in milk production and feed efficiency during lactation. Still, the milk's fatty acid (FA) profile showed increased levels of long-chain fatty acids, n3 and n6 polyunsaturated fatty acids. All these results suggest that methionine supplementation in early life can modify ewes' milk fatty acid profile without compromising feed efficiency. However, it is necessary to clarify whether this effect is passed on to the offspring (F1) through epigenetic marks in the germline.