Background: Diarrheagenic Escherichia coli (DEC) strains are a main cause of diarrhea worldwide in children under 5 years old. DEC virulence is strongly regulated by environmental conditions and metabolites produced by the gut microbiota in the intestinal tract. In this study, we evaluated changes in gut microbiota-metabolome in children with or without diarrhea produced by DEC pathotypes.

Goal: To determine gut microbiota composition and metabolome in stool samples obtained from healthy children and children with diarrhea positive for DEC pathotypes.

Methods: We analyzed a total of 16 age-paired stool samples: 8 diarrheal samples positive for one DEC pathotype and 8 stool samples from healthy children. To identify the microbiota composition, we sequenced the V3-V4 region of the 16S rRNA and determined operational phylogenetic units (OPU). OPU were then used to predict metabolic pathways using the PICRUSt2 software. The presence of metabolites in stool samples was determined by LC-MS. A correlation analysis was performed with the main genera from each group and main metabolites. Bacteria associated with variance of main metabolites were identified using the MIMOSA2 software.

Results: DEC and healthy groups showed a statistically different microbiota composition. A decrease in Firmicutes together with an increase in Bacteroidetes and Proteobacteria was found in the DEC group compared to the healthy group. Metabolic pathway predictions based on microbiota diversity showed that pathways involved in histidine and L-ornithine metabolism were significantly different between groups. A total of 88 metabolites detected by LC-MS were included in the metabolome analysis. We found higher levels of histamine and lower levels of ornithine in DEC samples than in the healthy group. Histamine and L-ornithine were associated with a specific microbiota species and the corresponding metabolic pathways.

Conclusion: Stool samples from healthy children and children positive for DEC displayed a differential metabolome and microbiota composition. A strong correlation between a gut microbiota species and certain metabolites, such as histamine and L-ornithine, was found in the DEC group. This information might be useful to identify mechanisms and signaling molecules involved in the crosstalk between microbiota and DEC pathotypes.

背景： 引起腹泻 大肠杆菌（DEC）菌株是全世界5岁以下儿童腹泻的主要原因。DEC毒力受环境条件和肠道微生物群产生的代谢产物的强烈调节。在这项研究中，我们评估了DEC致病型腹泻患儿肠道微生物群代谢组的变化。

目标： 为了确定粪便样本中的肠道微生物群组成和代谢组，这些样本取自健康儿童和腹泻儿童（DEC型阳性）。

方法：我们分析了总共16个年龄配对的粪便样本：一种DEC病态呈阳性的8个腹泻样本和来自健康儿童的8个粪便样本。为了鉴定微生物群组成，我们对16S rRNA的V3-V4区域进行了测序，并确定了系统发育系统单位（OPU）。然后使用PICRUSt2软件将OPU用于预测代谢途径。通过LC-MS确定粪便样品中代谢产物的存在。对各组的主要属和主要代谢物进行了相关分析。使用MIMOSA2软件可以识别与主要代谢物变异相关的细菌。

结果：DEC和健康组显示出统计学上不同的微生物群组成。减少坚定 以及增加 拟杆菌属 和 变形细菌与健康组相比，DEC组被发现。基于微生物群多样性的代谢途径预测表明，组之间参与组氨酸和L-鸟氨酸代谢的途径存在显着差异。通过LC-MS检测到的总共88种代谢物包括在代谢组分析中。我们发现，与健康组相比，DEC样品中的组胺水平较高，而鸟氨酸水平较低。组胺和L-鸟氨酸与特定的微生物群和相应的代谢途径有关。

结论：健康儿童和DEC阳性儿童的粪便样本显示出不同的代谢组和微生物群组成。在DEC组中发现肠道菌群物种与某些代谢物（例如组胺和L-鸟氨酸）之间存在很强的相关性。该信息可能有助于鉴定参与微生物群和DEC病态型之间的串扰的机制和信号分子。