Pathogenic enterotoxigenic Escherichia coli (ETEC) has been considered a major cause of diarrhea which is a serious public health problem in humans and animals. This study was aimed at examining the effect of γ-aminobutyric acid (GABA) supplementation on intestinal secretory immunoglobulin A (SIgA) secretion and gut microbiota profile in healthy and ETEC-infected weaning piglets. A total of thirty-seven weaning piglets were randomly distributed into two groups fed with the basal diet or supplemented with 40 mg·kg⁻¹ of GABA for three weeks, and some piglets were infected with ETEC at the last week. According to whether ETEC was inoculated or not, the experiment was divided into two stages (referred as CON1 and CON2 and GABA1 and GABA2). The growth performance, organ indices, amino acid levels, and biochemical parameters of serum, intestinal SIgA concentration, gut microbiota composition, and intestinal metabolites were analyzed at the end of each stage. We found that, in both the normal and ETEC-infected piglets, jejunal SIgA secretion and expression of some cytokines, such as IL-4, IL-13, and IL-17, were increased by GABA supplementation. Meanwhile, we observed that some low-abundance microbes, like Enterococcus and Bacteroidetes, were markedly increased in GABA-supplemented groups. KEGG enrichment analysis revealed that the nitrogen metabolism, sphingolipid signaling pathway, sphingolipid metabolism, and microbial metabolism in diverse environments were enriched in the GABA1 group. Further analysis revealed that alterations in microbial metabolism were closely correlated to changes in the abundances of Enterococcus and Bacteroidetes. In conclusion, GABA supplementation can enhance intestinal mucosal immunity by promoting jejunal SIgA secretion, which might be related with the T-cell-dependent pathway and altered gut microbiota structure and metabolism.

中文翻译：

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GABA 补充剂对健康和 ETEC 感染断奶仔猪肠道 SIgA 分泌和肠道微生物群的影响。

致病性肠毒素大肠杆菌（ETEC）被认为是腹泻的主要原因，腹泻是人类和动物的严重公共卫生问题。本研究旨在研究补充γ-氨基丁酸 (GABA) 对健康和 ETEC 感染断奶仔猪肠道分泌型免疫球蛋白 A (SIgA) 分泌和肠道微生物群特征的影响。将37头断奶仔猪随机分为两组，饲喂基础日粮或添加40 mg·kg ^-1 GABA，饲喂3周，最后一周部分仔猪感染ETEC。根据是否接种ETEC，实验分为两个阶段（简称CON1和CON2以及GABA1和GABA2）。在每个阶段结束时分析生长性能、器官指数、氨基酸水平和血清生化参数、肠道SIgA浓度、肠道微生物群组成和肠道代谢物。我们发现，在正常仔猪和感染 ETEC 的仔猪中，补充 GABA 都会增加空肠 SIgA 的分泌和一些细胞因子（如 IL-4、IL-13 和 IL-17）的表达。同时，我们观察到一些低丰度的微生物，如肠球菌和拟杆菌，在补充 GABA 的组中显着增加。KEGG富集分析显示，GABA1组富集了不同环境下的氮代谢、鞘脂信号通路、鞘脂代谢和微生物代谢。进一步分析表明，微生物代谢的变化与肠球菌和拟杆菌丰度的变化密切相关。总之，补充GABA可以通过促进空肠SIgA分泌来增强肠粘膜免疫，这可能与T细胞依赖性途径和改变肠道菌群结构和代谢有关。