Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada.
J Nutr. 2022 Aug 9;152(8):1843-1850. doi: 10.1093/jn/nxac095.
Parenteral nutrition (PN) is often a necessity for preterm infants; however, prolonged PN leads to gut atrophy, weakened gut barrier function, and a higher risk of intestinal infections. Peptide transporter-1 (PepT1) is a di- or tripeptide transporter in the gut and, unlike other nutrient transporters, its activity is preserved with the onset of intestinal atrophy from PN. As such, enteral amino acids in the form of dipeptides may be more bioavailable than free amino acids when atrophy is present.
In Yucatan miniature piglets with PN-induced intestinal atrophy, we sought to determine the structural and functional effects of enteral refeeding with lysine as a dipeptide, compared to free L-lysine.
Piglets aged 7-8 days were PN-fed for 4 days to induce intestinal atrophy, then were refed with enteral diets with equimolar lysine supplied as lysyl-lysine (Lys-Lys; n = 7), free lysine (n = 7), or Lys-Lys with glycyl-sarcosine (n = 6; to determine whether competitive inhibition of Lys-Lys uptake would abolish PepT1-mediated effects). The diets provided lysine at 75% of the requirement and were gastrically delivered for a total of 18 hours. Whole-body and tissue-specific protein synthesis, as well as indices for gut structure and barrier function, were measured.
The villus height, mucosal weight, and free lysine concentration were higher in the Lys-Lys group compared to the other 2 groups (P < 0.05). Lysyl-lysine led to greater whole-body protein synthesis compared to free lysine (P < 0.05). Mucosal myeloperoxidase activity was lower in the Lys-Lys group (P < 0.05), suggesting less inflammation. The inclusion of glycyl-sarcosine with Lys-Lys abolished the dipeptide effects on whole-body and tissue-specific protein synthesis (P < 0.05), suggesting that improved lysine availability was mediated by PepT1.
Improved intestinal structure and whole-body protein synthesis suggests that feeding strategies designed to exploit PepT1 may help to avoid adverse effects when enteral nutrition is reintroduced into the compromised guts of neonatal piglets.
肠外营养（PN）通常是早产儿的必需品；然而，长期的 PN 会导致肠道萎缩、肠道屏障功能减弱，以及肠道感染的风险增加。肽转运蛋白 1（PepT1）是肠道中的二肽或三肽转运体，与其他营养物转运体不同，其活性在 PN 引起的肠道萎缩时得以保留。因此，在存在萎缩的情况下，以二肽形式存在的肠内氨基酸可能比游离氨基酸更具生物利用度。
在 PN 诱导的肠道萎缩的尤卡坦微型猪中，我们试图确定肠内再喂养赖氨酸二肽与游离 L-赖氨酸相比对肠道结构和功能的影响。
7-8 日龄仔猪接受 PN 喂养 4 天以诱导肠道萎缩，然后接受肠内喂养，用等摩尔赖氨酸提供赖氨酸-赖氨酸（Lys-Lys；n = 7）、游离赖氨酸（n = 7）或赖氨酸-赖氨酸与甘氨酰-肌氨酸（n = 6；以确定竞争抑制 Lys-Lys 摄取是否会消除 PepT1 介导的作用）。饮食提供 75%的赖氨酸需求，并通过胃内输送持续 18 小时。测量全身和组织特异性蛋白质合成以及肠道结构和屏障功能的指标。
与其他 2 组相比，Lys-Lys 组的绒毛高度、黏膜重量和游离赖氨酸浓度更高（P < 0.05）。与游离赖氨酸相比，Lys-Lys 导致全身蛋白质合成更高（P < 0.05）。Lys-Lys 组的黏膜髓过氧化物酶活性较低（P < 0.05），提示炎症较少。与 Lys-Lys 一起添加甘氨酰-肌氨酸消除了二肽对全身和组织特异性蛋白质合成的作用（P < 0.05），表明赖氨酸可用性的提高是由 PepT1 介导的。
改善的肠道结构和全身蛋白质合成表明，设计利用 PepT1 的喂养策略可能有助于避免新生儿仔猪受损肠道重新接受肠内营养时的不良影响。
