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other·gastroenterology, immunology, nutrition, clinical nutrition, epidemiology·PMC10469184

Downregulated APOD and FCGR2A correlates with immune infiltration and lipid-induced symptoms of irritable bowel syndrome

Scientific Reports · 8 authors, 2 centres

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TL;DR

This study analyzed a public gene expression dataset and clinical data to identify genes linked to lipid-induced irritable bowel syndrome (IBS) symptoms. It found that lower expression of APOD and FCGR2A genes in the small intestine and blood is associated with IBS and may serve as diagnostic biomarkers.

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This study combined a clinical questionnaire analysis of IBS patients with a bioinformatic reanalysis of the GSE166869 dataset from small intestinal mucosa after lipid infusion. The clinical analysis showed that increased fat intake was associated with higher IBS risk and symptom severity. Bioinformatic analysis identified 116 differentially expressed genes mainly in immune and inflammatory pathways, with higher infiltration of Neutrophils, CD4+ T cells, and M1 Macrophages in IBS patients. Five hub genes were selected using machine learning algorithms. After laboratory verification, only APOD and FCGR2A were consistently downregulated in the small intestinal mucosa and plasma of IBS patients. The combination of APOD and FCGR2A expression showed a diagnostic area under the curve of 0.9. The study suggests these genes may be protective factors and promising biomarkers for lipid-sensitive IBS.

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other

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gastroenterology

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ORIGINAL PAPER

PMC10469184

Downregulated APOD and FCGR2A correlates with immune infiltration and lipid-induced symptoms of irritable bowel syndrome

Scientific Reports

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ABSTRACT

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.

CITATION EXPORT

Yamei Ran, Kangqi Wu, Chenglin Hu et al.. Downregulated APOD and FCGR2A correlates with immune infiltration and lipid-induced symptoms of irritable bowel syndrome. Scientific Reports. (2023). https://doi.org/10.1038/s41598-023-41004-9

AUTHORS

8 · 2 CENTRES

Yamei Ran, Kangqi Wu, Chenglin Hu, Renzheng Liang, Li Zhang, Juan Xiao, Yongmei Peng, Wenjing Sun

1Department of Gastroenterology and Hepatology, Thirteenth People’s Hospital of Chongqing (Chongqing Geriatric Hospital), Chongqing, 400053 China
2https://ror.org/00hagsh42grid.464460.4Department of Standardization Training Management, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400021 China