Department of Gastroenterology and Hepatology, Thirteenth People's Hospital of Chongqing (Chongqing Geriatric Hospital), Chongqing, 400053, China.
Department of Standardization Training Management, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400021, China.
Sci Rep. 2023 Aug 30;13(1):14211. doi: 10.1038/s41598-023-41004-9.
Fat intake is among the most significant triggers for symptom development in patients with irritable bowel syndrome (IBS). Nevertheless, long-term restriction in fatty foods ingestion may lead to nutritional inadequacies. This study aimed to identify the crucial genes involved in lipid-induced gastrointestinal symptoms, contributing to helping IBS patients regulate fat. The clinical characteristics of the subjects were collected by questionnaire investigation and analyzed using multivariate logistic regression. Differentially expressed genes (DEG) and signaling pathways were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. ImmuInfiltration and CIBERSORT packages evaluated small intestine immune cell infiltration. Random forest and SVM-RFE algorithms were used to select hub genes. A receiver operating characteristic curve was used to access the diagnostic significance of each hub gene. Gene Set Enrichment Analysis (GSEA) was performed to identify hub genes' molecular processes in IBS development after lipid infusion. IBS patients' risk, severity, and quality of life increased with fat intake. In total, 116 robust DEGs were identified in IBS patients after lipid infusion using the GSE166869 dataset and were mainly clustered in the immune and inflammatory pathways. IBS patients had greater Neutrophils, CD4 T cells, and M1 Macrophages than healthy controls. Furthermore, infiltration levels of Neutrophils and resting memory CD4 T cells were inversely related to the expression of hub genes (IGKV1D-43, IGKV1-12, APOD, FCGR2A and IGKV2-29). After lipid infusion, GSEA results of each hub gene indicated the relevance of proinflammatory pathways in IBS pathogenesis. After verification, only APOD and FCGR2A were stably downregulated in small intestinal mucosa and plasma of IBS patients. The area under the curve of APOD combined with FCGR2A expression was 0.9. APOD and FCGR2A may be promising biomarkers for IBS diagnosis and lipid-sensitive IBS patients. Their potential roles in the immune microenvironment of the small intestinal mucosa may provide a vital clue to IBS precision therapy.
脂肪摄入是导致肠易激综合征（IBS）患者症状发展的最重要因素之一。然而，长期限制脂肪食物的摄入可能导致营养不足。本研究旨在确定与脂质诱导的胃肠道症状相关的关键基因，以帮助 IBS 患者调节脂肪。通过问卷调查收集受试者的临床特征，并采用多变量逻辑回归进行分析。通过基因本体论和京都基因与基因组百科全书通路富集分析对差异表达基因（DEG）和信号通路进行分析。ImmuInfiltration 和 CIBERSORT 包评估小肠免疫细胞浸润。随机森林和 SVM-RFE 算法用于选择枢纽基因。使用接收者操作特征曲线评估每个枢纽基因的诊断意义。进行基因集富集分析（GSEA）以识别脂质输注后 IBS 发展中枢纽基因的分子过程。随着脂肪摄入的增加，IBS 患者的风险、严重程度和生活质量增加。使用 GSE166869 数据集，共鉴定出 116 个在脂质输注后 IBS 患者中具有稳健表达差异的基因，这些基因主要聚类在免疫和炎症途径中。与健康对照组相比，IBS 患者的中性粒细胞、CD4 T 细胞和 M1 巨噬细胞较多。此外，中性粒细胞和静息记忆 CD4 T 细胞的浸润水平与枢纽基因（IGKV1D-43、IGKV1-12、APOD、FCGR2A 和 IGKV2-29）的表达呈负相关。脂质输注后，每个枢纽基因的 GSEA 结果表明促炎途径在 IBS 发病机制中的相关性。验证后，只有 APOD 和 FCGR2A 在 IBS 患者的小肠黏膜和血浆中稳定下调。APOD 与 FCGR2A 表达相结合的曲线下面积为 0.9。APOD 和 FCGR2A 可能是 IBS 诊断和脂质敏感 IBS 患者的有前途的生物标志物。它们在小肠黏膜免疫微环境中的潜在作用可能为 IBS 精准治疗提供重要线索。
