Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrhea in children and travelers, especially in low- and middle-income countries. ETEC is a non-invasive gut pathogen colonizing the small intestinal wall before secreting diarrhea-inducing enterotoxins. We sought to investigate the impact of ETEC infection on local and systemic host defenses by examining plasma markers of inflammation and mucosal injury as well as kynurenine pathway metabolites. Plasma samples from 21 volunteers experimentally infected with ETEC were collected before and 1, 2, 3, and 7 days after ingesting the ETEC dose, and grouped based on the level of intestinal ETEC proliferation: 14 volunteers experienced substantial proliferation (SP) and 7 had low proliferation (LP). Plasma markers of inflammation, kynurenine pathway metabolites, and related cofactors (vitamins B2 and B6) were quantified using targeted mass spectrometry, whereas ELISA was used to quantify the mucosal injury markers, regenerating islet-derived protein 3A (Reg3a), and intestinal fatty acid-binding protein 2 (iFABP). We observed increased concentrations of plasma C-reactive protein (CRP), serum amyloid A (SAA), neopterin, kynurenine/tryptophan ratio (KTR), and Reg3a in the SP group following dose ingestion. Vitamin B6 forms, pyridoxal 5'-phosphate and pyridoxal, decreased over time in the SP group. CRP, SAA, and pyridoxic acid ratio correlated with ETEC proliferation levels. The changes following experimental ETEC infection indicate that ETEC, despite causing a non-invasive infection, induces systemic inflammation and mucosal injury when proliferating substantially, even in cases without diarrhea. It is conceivable that ETEC infections, especially when repeated, contribute to negative health impacts on children in ETEC endemic areas.

产肠毒素大肠杆菌(ETEC) 是儿童和旅行者腹泻的重要原因，尤其是在低收入和中等收入国家。ETEC 是一种非侵入性肠道病原体，在分泌引起腹泻的肠毒素之前定植于小肠壁。我们试图通过检查炎症和粘膜损伤的血浆标志物以及犬尿氨酸途径代谢物来研究 ETEC 感染对局部和全身宿主防御的影响。在摄入 ETEC 剂量之前和之后 1、2、3 和 7 天收集了 21 名实验感染 ETEC 的志愿者的血浆样本，并根据肠道 ETEC 增殖水平进行分组：14 名志愿者经历了实质性增殖 (SP)，7 名志愿者经历了显着增殖 (SP)。低增殖（LP）。使用靶向质谱法对炎症、犬尿氨酸途径代谢物和相关辅因子（维生素 B2 和 B6）的血浆标记物进行定量，而 ELISA 用于对粘膜损伤标记物、再生胰岛衍生蛋白 3A (Reg3a) 和肠脂肪酸进行定量-结合蛋白2 (iFABP)。我们观察到 SP 组在服用剂量后血浆 C 反应蛋白 (CRP)、血清淀粉样蛋白 A (SAA)、新蝶呤、犬尿氨酸/色氨酸比率 (KTR) 和 Reg3a 浓度增加。SP组中维生素B6的形式、5'-磷酸吡哆醛和吡哆醛随着时间的推移而减少。CRP、SAA 和吡哆酸比率与 ETEC 增殖水平相关。实验性 ETEC 感染后的变化表明，ETEC 尽管会引起非侵入性感染，但在大量增殖时会诱发全身炎症和粘膜损伤，即使在没有腹泻的情况下也是如此。可以想象，ETEC 感染，尤其是反复感染，会对 ETEC 流行地区的儿童健康造成负面影响。