Understanding the impact of neonatal glutamine supplementation on the interaction between gut epithelia, its mitochondria, and microbiota, and its importance for the development in low birthweight piglets

了解新生儿谷氨酰胺补充剂对肠道上皮、线粒体和微生物群之间相互作用的影响，及其对低出生体重仔猪发育的重要性

• 批准号: 396713213
• 负责人: Professorin Dr. Cornelia C. Metges
• 金额: --
• 依托单位: Institut für Ernährungsphysiologie "Oskar Kellner"
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/396713213?language=en
• 关键词: Understanding; impact; neonatal; glutamine; supplementation

With breeding for increasing litter size, approximately 10-20% of piglets within a litter are affected by low birthweight (LBW) and/or intrauterine growth restriction (IUGR), and the overall pre-weaning piglet mortality is up to 35%. This is ethically unacceptable, and grossly inefficient. Piglet LBW and IUGR are associated to lower postnatal growth, reduced intestinal size and maturity, impaired gut barrier function and mucosal immunity. It has been shown that increased intestinal permeability is associated with poor mitochondrial functions. Intake and composition of colostrum and milk play a major role in the stimulation and regulation of body and intestinal growth and development during early life as well as the functional maturation of the microbiome in suckling piglets. The microbiome releases metabolites that may affect host mitochondrial energy metabolism. In contrast to normal-weight litter mates, LBW and/or IUGR piglets have lower energy reserves and delayed access to colostrum intake immediately after birth, and thus, tailored nutritional solutions for young pigs might be a means to optimize gut health and development. One gut-friendly nutrient might be glutamine (GLN), which can improve intestinal and whole body growth and development, and prevent intestinal oxidative injury and inflammatory disease when given to piglets shortly before or after weaning. Thus a case was made for beneficial effects of additional GLN intake beyond its provision with milk, which might be particularly useful in this phase of life especially in IUGR piglets. There is suggestive evidence that the provision of additional dietary GLN could be beneficial to intestinal development, and mitochondrial function in suckling neonatal pigs. However, whether there is an interaction between GLN supplementation, intestinal microbiota, their metabolites and host mitochondria in suckling piglets which play a role for gut function is still poorly understood. The goal of the proposed collaborative research is to investigate whether early life GLN supplementation impacts the gut in a beneficial way. Moreover, we aim to understand the interaction of gut epithelium and its mitochondria with microbiota acutely and in the longer-term (after weaning). We will thus characterize the intestinal epithelium (mitochondria characteristics, proliferation, local defense mechanisms, amino acid and glutathione metabolism) and the microbiome composition and its metabolic activity at functional and molecular levels. In an overarching evaluation, we will determine components explaining the variation and delineate relationships between intestinal mitochondria transcriptome and microbiota, mitochondrial and intestinal trait complexes, microbiota and intestinal trait complexes, as well as GLN metabolism. We expect to elucidate how these interactions are associated with the development and health of neonatal piglets.

随着产仔数的增加，一窝中约10-20%的仔猪受到低出生体重（LBW）和/或宫内生长受限（IUGR）的影响，断奶前仔猪的总体死亡率高达35%。这在道德上是不可接受的，而且效率极低。仔猪LBW和IUGR与仔猪出生后生长速度减慢、肠道尺寸和成熟度降低、肠道屏障功能和粘膜免疫功能受损有关。已经表明，肠通透性增加与线粒体功能差相关。初乳和乳汁的摄入和组成在哺乳仔猪生命早期的身体和肠道生长发育以及微生物组的功能成熟的刺激和调节中起着重要作用。微生物组释放可能影响宿主线粒体能量代谢的代谢物。与正常体重的同窝仔相比，LBW和/或IUGR仔猪的能量储备较低，出生后立即获得初乳摄入的时间较晚，因此，为仔猪量身定制的营养解决方案可能是优化肠道健康和发育的一种手段。谷氨酰胺（GLN）可能是一种肠道友好型营养素，它可以改善肠道和全身的生长和发育，并在断奶前或断奶后不久给予仔猪时预防肠道氧化损伤和炎症性疾病。因此，除了提供乳汁之外，额外摄入GLN也会产生有益影响，这在生命的这个阶段可能特别有用，尤其是对于IUGR小猪。有提示性证据表明，提供额外的饮食GLN可能有利于肠道发育和哺乳新生猪的线粒体功能。然而，是否有GLN补充，肠道菌群，其代谢产物和宿主线粒体之间的相互作用在哺乳仔猪肠道功能发挥作用仍然知之甚少。拟议的合作研究的目标是调查早期生活GLN补充剂是否以有益的方式影响肠道。此外，我们的目标是了解肠道上皮细胞及其线粒体与微生物群的相互作用，以及长期（断奶后）。因此，我们将在功能和分子水平上表征肠上皮（线粒体特征、增殖、局部防御机制、氨基酸和谷胱甘肽代谢）和微生物组组成及其代谢活性。在总体评估中，我们将确定解释肠道线粒体转录组和微生物群，线粒体和肠道性状复合体，微生物群和肠道性状复合体以及GLN代谢之间的变化和关系的组成部分。我们希望阐明这些相互作用是如何与新生仔猪的发育和健康。