Rosa Fernanda, Matazel Katelin S, Elolimy Ahmed A, Adams Sean H, Bowlin Anne, Williams Keith D, Bode Lars, Yeruva Laxmi
Arkansas Children's Nutrition Center, Little Rock, Arkansas, USA.
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
mSystems. 2021 Feb 9;6(1):e01376-20. doi: 10.1128/mSystems.01376-20.
The impact of human milk (HM) feeding compared with cow's milk formula (MF) feeding on small intestinal and circulatory metabolome patterns has not been fully investigated. Therefore, 2-day-old male piglets were fed HM or MF ( = 26/group) from postnatal day 2 (PND 2) through 21 and were weaned to a solid diet until PND 51. The small intestine (gastrointestinal [GI]) contents, serum, and urine were collected from subsets of piglets at PND 21 and PND 51. Samples were subjected to primary metabolomics analyses at the West Coast Metabolomics Center, UC Davis. The metabolome data assessment and the statistical analyses were performed with MetaboAnalyst software. Compared with MF feeding, at PND 21, HM feeding resulted in a higher abundance of fucose in the jejunum and urine and a greater concentration of myo-inositol in serum. In HM-fed piglets, 1,5-anhydroglucitol was higher in the duodenum, serum, and urine at PND 21. Additionally, the HM group had higher levels of urinary kynurenic acid at PND 21. Correlations between bacterial genera and altered metabolites in ileum revealed that sp. and sp. were positively correlated with maltotriose and panose at PND 21, while ileal sp. was negatively correlated with fumaric acid. At PND 51, no significant metabolites were identified between HM and MF diet groups. The metabolites associated with the neonatal diets may serve as the substrates and signals that contribute to the physiological effects in HM and MF during infancy, with a subset reflecting diet-associated differences in microbial metabolism and ecology. Exclusive HM feeding for newborns is recommended at least for the first 6 months of life. However, when breastfeeding is not possible, MF is recommended as a substitute. Due to the challenges associated with sample collection from infants fed HM or MF, their gut metabolism is poorly understood. Thus, an established piglet model from our team was used to determine the metabolite profile in relation to host, diet, and microbiota. The current study is the first to provide novel insights across the small intestine metabolism and its association with circulatory metabolites in the HM group relative to the MF group at the weaning and postweaning period. Data also demonstrate that during the neonatal period, diet, host, and microbial metabolism contribute to the lumen and circulatory metabolite profile. Furthermore, small intestinal lumen metabolome can be tracked in the urine as a biomarker of dietary differences, which would be a useful tool for clinical interventions.
与牛奶配方奶（MF）喂养相比，母乳（HM）喂养对小肠和循环代谢组模式的影响尚未得到充分研究。因此，从出生后第2天（PND 2）到21天，给2日龄雄性仔猪喂HM或MF（每组n = 26），并断奶改为固体饲料，直至PND 51。在PND 21和PND 51时，从仔猪亚组中收集小肠（胃肠道[GI]）内容物、血清和尿液。样本在加州大学戴维斯分校西海岸代谢组学中心进行初级代谢组学分析。代谢组数据评估和统计分析使用MetaboAnalyst软件进行。与MF喂养相比，在PND 21时，HM喂养导致空肠和尿液中岩藻糖丰度更高，血清中肌醇浓度更高。在PND 21时，在喂HM的仔猪中，十二指肠、血清和尿液中的1,5 - 脱水葡萄糖醇含量更高。此外，HM组在PND 21时尿中犬尿酸水平更高。回肠中细菌属与代谢物变化之间的相关性表明，在PND 21时，某菌属和某菌属与麦芽三糖和潘糖呈正相关，而回肠中的某菌属与富马酸呈负相关。在PND 51时，HM和MF饮食组之间未发现显著的代谢物。与新生儿饮食相关的代谢物可能作为底物和信号，有助于婴儿期HM和MF的生理效应，其中一部分反映了饮食相关的微生物代谢和生态差异。建议至少在出生后的前6个月对新生儿进行纯母乳喂养。然而，当无法进行母乳喂养时，建议用MF替代。由于从喂HM或MF的婴儿中采集样本存在挑战，人们对他们的肠道代谢了解甚少。因此，我们团队建立的仔猪模型用于确定与宿主、饮食和微生物群相关的代谢物谱。本研究首次提供了断奶期和断奶后期HM组相对于MF组在小肠代谢及其与循环代谢物的关联方面的新见解。数据还表明，在新生儿期，饮食、宿主和微生物代谢有助于管腔和循环代谢物谱的形成。此外，小肠管腔代谢组可以在尿液中追踪，作为饮食差异的生物标志物，这将是临床干预的一个有用工具。
