ABSTRACT

The neonatal intestinal tract is immature and can be easily infected by pathogens causing inflammation. Maternal diet manipulation is a promising nutritional strategy to enhance the gut health of offspring. A fermented diet is a gut microbiota targeting diet containing live probiotics and their metabolites, which benefit the gut and overall health host. However, it remains unclear how a maternal fermented diet (MFD) affects neonatal intestinal inflammation. Here, in vivo and in vitro models together with multi-omics analysis were applied to investigate the impacts and the underlying mechanism through which an MFD prevents from gut inflammation in neonates. An MFD remarkably improved the performance of both sows and piglets and significantly altered the gut microbiome and milk metabolome of sows. In addition, the MFD significantly accelerated the maturation of the gut microbiota of neonates and increased the abundance of gut Lactobacillus and the microbial functions of amino acid-related enzymes and glucose metabolism on the weaning day. Notably, the MFD reduced susceptibility to colonic inflammation in offspring. The fecal microbiota of sows was then transplanted into mouse dams and it was found that the mouse dams and pups in the MFD group alleviated the LPS-induced decrease in gut Lactobacillus abundance and barrier injury. Milk L-glutamine (GLN) and gut Lactobacillus reuteri (LR) were found as two of the main MFD-induced sow effectors that contributed to the gut health of piglets. The properties of LR and GLN in modulating gut microbiota and alleviating colonic inflammation by inhibiting the phosphorylation of p38 and JNK and activation of Caspase 3 were further verified. These findings provide the first data revealing that an MFD drives neonate gut microbiota development and ameliorates the colonic inflammation by regulating the gut microbiota. This fundamental evidence might provide references for modulating maternal nutrition to enhance early-life gut health and prevent gut inflammation.

摘要

新生儿肠道不成熟，很容易被引起炎症的病原体感染。母体饮食控制是一种很有前途的营养策略，可以增强后代的肠道健康。发酵饮食是一种针对肠道微生物群的饮食，含有活益生菌及其代谢物，有益于肠道和整体健康宿主。然而，目前尚不清楚母体发酵饮食 (MFD) 如何影响新生儿肠道炎症。在这里，体内和体外模型与多组学分析一起用于研究 MFD 预防新生儿肠道炎症的影响和潜在机制。MFD 显着改善了母猪和仔猪的生产性能，并显着改变了母猪的肠道微生物组和乳汁代谢组。此外，MFD显着加速了新生儿肠道菌群的成熟，增加了断奶日肠道乳酸菌的丰度以及氨基酸相关酶和葡萄糖代谢的微生物功能。值得注意的是，MFD 降低了后代对结肠炎症的易感性。然后将母猪的粪便微生物群移植到母鼠体内，发现 MFD 组的母鼠和幼仔缓解了 LPS 引起的肠道减少乳酸菌丰度和屏障损伤。发现牛奶 L-谷氨酰胺 (GLN) 和肠道罗伊氏乳杆菌(LR) 是 MFD 诱导的两种主要的母猪效应物，有助于仔猪的肠道健康。进一步验证了 LR 和 GLN 通过抑制 p38 和 JNK 的磷酸化以及 Caspase 3 的活化来调节肠道微生物群和减轻结肠炎症的特性。这些发现提供了第一个数据，揭示了 MFD 驱动新生儿肠道微生物群的发育并通过调节肠道微生物群来改善结肠炎症。这一基本证据可能为调节母体营养以增强早期肠道健康和预防肠道炎症提供参考。