Impact of medium- and long-chain triacylglycerols and sn-2 palmitate on temperament development in term infants: potential role of gut Bifidobacterium

Abstract

Background: Medium- and long-chain triacylglycerols (MLCTs) and sn-2 palmitate constitute 70–80% of human breast milk lipids. Our previous work showed that a formula supplemented with these structural lipids promoted adequate weight gain, but their effects on neuropsychological development and gut microbiome remain unclear. Therefore, this study aimed to investigate the effects of supplementation with MLCTs and sn-2 palmitate on temperament development and the gut microbiome in term infants. Methods: This was a prospective, parallel, open-label controlled trial. Infants were divided into three groups according to their feeding patterns at the 4^th week postpartum: the intervention group received a formula supplemented with MLCTs and sn-2 palmitate (IG, n = 65), the control group received a formula without these lipids (CG, n = 48), and the breastfed group (BG, n = 66). Assessment of infant temperament was conducted at the baseline (1 month postpartum) and endpoint (3 months postpartum) using the Early Infancy Temperament Questionnaire. Stool samples were collected concurrently for microbiome analysis via 16S rRNA amplicon sequencing. Results: After two months of intervention, the IG exhibited significant improvements in temperament scores compared to the CG, including activity (p = 0.039), mood (p = 0.023), persistence (p = 0.001), and distractibility (p = 0.006), but similar changes to the BG. As for the gut microbiome, the relative abundance of Bifidobacterium in the IG was significantly increased compared to the CG (p = 0.011) and was comparable to the BG (p = 0.759). Conversely, the decrease in the relative abundance of Blautia was significantly more pronounced in the IG than in both the CG (p = 0.002) and BG (p = 0.048). Furthermore, temperament characteristics were associated with microbiome genera in early infancy. Notably, a positive correlation was observed between the changes in activity scores and the relative abundance of Bifidobacterium (r = 0.25, p = 0.002). Conclusions: The intervention involving MLCTs and sn-2 palmitate improves infant temperament, potentially mediated via increased Bifidobacterium. These findings highlight the potential of nutrition to alter the infant temperament by modulating the gut microbiome, offering valuable insights for the development of optimized nutritional strategies to support neurodevelopment. The clinical trial registry number is NCT05295030 (https://clinicaltrials.gov).