Section for Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg C, DK-1870, Denmark; Department of Food Science, University of Copenhagen, Frederiksberg, DK-1985, Denmark.
Section for Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg C, DK-1870, Denmark.
Clin Nutr. 2024 Dec;43(12):405-414. doi: 10.1016/j.clnu.2024.11.005. Epub 2024 Nov 6.
BACKGROUND & AIMS: Human milk is the optimal diet for very preterm infants (VPIs), but it requires nutrient fortification to support growth. Bovine colostrum (BC), rich in intact proteins and bioactive components, could serve as a novel fortifier with potential benefits to VPIs gut health. To evaluate a possible effect of feeding BC on intestinal metabolism, the gut microbiota, and their interaction, we studied the fecal metabolome of VPIs in the first month of life, as compared with a conventional fortifier (CF, based on infant formula ingredients).
Fecal samples were collected from VPIs recruited to the FortiColos trial (NCT03537365, BC, n = 107; CF, n = 112) before (FT0) and one (FT1) or two (FT2) weeks after start of fortification and analyzed using H NMR spectroscopy. Abundances of metabolites were compared between BC versus CF groups. Further, temporal changes in metabolite levels after start of fortification, as well as correlations with specific gut bacterial genera were explored.
Infants in the BC group had higher levels of fecal acetoacetate, choline, methanol, uracil, creatine, creatinine, lysine and a lower leucine at both FT1 and FT2, relative to the CF group. Asparagine, tryptophan and phenylalanine levels were higher, and butyrate was lower in the BC group at FT1. At FT2, higher fecal succinate and lower isoleucine were found in the BC group. In addition, eight metabolites (asparagine, phenylalanine, tryptophan, lysine, creatinine, acetoacetate, methanol and uracil) had fortification-specific changes over time. Positive correlations were found between succinate and unclassified Enterobacteriaceae, butyrate and Clostridium, uracil and Staphylococcus, while negative correlation were found between uracil and unclassified Enterobacteriaceae members.
Our study shows distinct fecal metabolome profiles in VPIs in the first weeks after fortification with BC versus CF. The fortification- and time-specific gut metabolite changes suggest that fortifiers influence luminal nutrient metabolism and microbiota activity in VPIs. Fortifier type for human milk affected gut health of VPIs via altered gut metabolite levels, interacting with microbiota in VPIs.
母乳是极早产儿（VPIs）的最佳饮食，但为了支持生长，需要对其进行营养强化。牛初乳（BC）富含完整的蛋白质和生物活性成分，可作为一种新型强化剂，对 VPIs 的肠道健康可能有益。为了评估喂养 BC 对肠道代谢、肠道微生物群及其相互作用的可能影响，我们研究了 VPIs 在生命的第一个月的粪便代谢组，与传统强化剂（基于婴儿配方成分的 CF）进行比较。
从参加 FortiColos 试验（NCT03537365，BC 组 n=107；CF 组 n=112）的 VPIs 中收集粪便样本，在强化开始前（FT0）和强化开始后 1 周（FT1）或 2 周（FT2）进行分析，采用 H NMR 光谱法。比较 BC 组与 CF 组之间代谢物的丰度。进一步探索强化开始后代谢物水平的时间变化，以及与特定肠道细菌属的相关性。
与 CF 组相比，BC 组婴儿在 FT1 和 FT2 时粪便中的乙酰乙酸、胆碱、甲醇、尿嘧啶、肌酸、肌酐、赖氨酸水平更高，亮氨酸水平更低。在 FT1 时，BC 组的天冬酰胺、色氨酸和苯丙氨酸水平更高，丁酸盐水平更低。在 FT2 时，BC 组粪便中的琥珀酸盐水平更高，异亮氨酸水平更低。此外，有 8 种代谢物（天冬酰胺、苯丙氨酸、色氨酸、赖氨酸、肌酐、乙酰乙酸、甲醇和尿嘧啶）具有强化特异性的时间变化。在 VPIs 中，琥珀酸盐与未分类肠杆菌科呈正相关，丁酸盐与梭菌属呈正相关，尿嘧啶与葡萄球菌属呈正相关，而尿嘧啶与未分类肠杆菌科成员呈负相关。
我们的研究表明，在 VPIs 用 BC 与 CF 强化后的最初几周内，粪便代谢组图谱存在明显差异。强化和时间特异性的肠道代谢物变化表明，强化剂会影响 VPIs 腔内营养代谢和微生物群的活性。人乳的强化剂类型通过改变 VPIs 中的肠道代谢物水平，与肠道微生物群相互作用，影响 VPIs 的肠道健康。
