Seesandra V. Rajagopala, Meghan H. Shilts, Hernan Correa, Suman R. Das, Yash A. Choksi, Justin Jacobse, Jeremy A. Goettel, Girish Hiremath
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METHODS Using metatranscriptomics, the host transcriptional and active microbial profiles were captured from 17 esophageal biopsy samples (PPI naïve [PPI−], n = 7; PPI exposed [PPI+], n = 10) collected from children without any endoscopic and histologic abnormalities in their esophagus (normal esophagus). Deconvolution computational analysis was performed with xCell to assess if the observed epithelial gene expression changes were related to the cell type composition in the esophageal samples. RESULTS The median (IQR) age of our cohort was 14 years (12–16) with female (63%) preponderance. Both groups were similar in terms of their demographics and clinical features. Compared with PPI−, the PPI+ had upregulation of 27 genes including the MUC genes. The cell type composition was similar between the PPI− and PPI+ groups. Prevotella sp and Streptococcus sp were abundant in PPI+ group. CONCLUSIONS In children with normal esophagus, PPI exposure can be associated with upregulation of esophageal mucosal homeostasis and epithelial cell function genes in a cell-type independent manner, and an altered esophageal microbiome. Additional studies are warranted to validate our findings and to investigate the causal effect of PPIs on the normal esophageal epithelium and microbial communities.","PeriodicalId":22794,"journal":{"name":"The Journal of Pediatric Pharmacology and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Proton Pump Inhibitors Modulate Gene Expression Profile in Esophageal Mucosa and Microbiome\",\"authors\":\"Seesandra V. Rajagopala, Meghan H. Shilts, Hernan Correa, Suman R. Das, Yash A. Choksi, Justin Jacobse, Jeremy A. Goettel, Girish Hiremath\",\"doi\":\"10.5863/1551-6776-28.6.504\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"OBJECTIVE Proton pump inhibitors (PPIs) are commonly used to manage children with upper gastrointestinal symptoms and without a formal diagnosis. We investigated the effect of PPIs on esophageal mucosal transcriptome and active microbiota in children with normal esophagi. Furthermore, we examined whether the differences in host esophageal mucosal gene expression were driven by an underlying esophageal epithelial cell type composition. METHODS Using metatranscriptomics, the host transcriptional and active microbial profiles were captured from 17 esophageal biopsy samples (PPI naïve [PPI−], n = 7; PPI exposed [PPI+], n = 10) collected from children without any endoscopic and histologic abnormalities in their esophagus (normal esophagus). Deconvolution computational analysis was performed with xCell to assess if the observed epithelial gene expression changes were related to the cell type composition in the esophageal samples. RESULTS The median (IQR) age of our cohort was 14 years (12–16) with female (63%) preponderance. Both groups were similar in terms of their demographics and clinical features. Compared with PPI−, the PPI+ had upregulation of 27 genes including the MUC genes. The cell type composition was similar between the PPI− and PPI+ groups. Prevotella sp and Streptococcus sp were abundant in PPI+ group. CONCLUSIONS In children with normal esophagus, PPI exposure can be associated with upregulation of esophageal mucosal homeostasis and epithelial cell function genes in a cell-type independent manner, and an altered esophageal microbiome. Additional studies are warranted to validate our findings and to investigate the causal effect of PPIs on the normal esophageal epithelium and microbial communities.\",\"PeriodicalId\":22794,\"journal\":{\"name\":\"The Journal of Pediatric Pharmacology and Therapeutics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Journal of Pediatric Pharmacology and Therapeutics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.5863/1551-6776-28.6.504\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Pediatric Pharmacology and Therapeutics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.5863/1551-6776-28.6.504","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
目的质子泵抑制剂(PPIs)通常用于治疗没有正式诊断的上胃肠道症状的儿童。我们研究了PPIs对正常食管儿童食管黏膜转录组和活性微生物群的影响。此外,我们研究了宿主食管粘膜基因表达的差异是否由潜在的食管上皮细胞类型组成驱动。方法采用亚转录组学方法,从17份食管活检样本中捕获宿主转录和活性微生物谱(PPI naïve [PPI−],n = 7;PPI暴露[PPI+], n = 10)采集自食管无任何内镜和组织学异常的儿童(正常食管)。使用xCell进行反褶积计算分析,以评估观察到的上皮基因表达变化是否与食管样本中细胞类型组成有关。结果我们队列的中位(IQR)年龄为14岁(12-16岁),女性(63%)占优势。两组在人口统计学和临床特征方面相似。与PPI−相比,PPI+上调了包括MUC基因在内的27个基因。PPI -组和PPI+组细胞类型组成相似。PPI+组富含普雷沃氏菌和链球菌。结论:在食管正常的儿童中,PPI暴露可能与食管黏膜稳态和上皮细胞功能基因以细胞类型独立的方式上调以及食管微生物群改变有关。需要进一步的研究来验证我们的发现,并调查PPIs对正常食管上皮和微生物群落的因果影响。
Proton Pump Inhibitors Modulate Gene Expression Profile in Esophageal Mucosa and Microbiome
OBJECTIVE Proton pump inhibitors (PPIs) are commonly used to manage children with upper gastrointestinal symptoms and without a formal diagnosis. We investigated the effect of PPIs on esophageal mucosal transcriptome and active microbiota in children with normal esophagi. Furthermore, we examined whether the differences in host esophageal mucosal gene expression were driven by an underlying esophageal epithelial cell type composition. METHODS Using metatranscriptomics, the host transcriptional and active microbial profiles were captured from 17 esophageal biopsy samples (PPI naïve [PPI−], n = 7; PPI exposed [PPI+], n = 10) collected from children without any endoscopic and histologic abnormalities in their esophagus (normal esophagus). Deconvolution computational analysis was performed with xCell to assess if the observed epithelial gene expression changes were related to the cell type composition in the esophageal samples. RESULTS The median (IQR) age of our cohort was 14 years (12–16) with female (63%) preponderance. Both groups were similar in terms of their demographics and clinical features. Compared with PPI−, the PPI+ had upregulation of 27 genes including the MUC genes. The cell type composition was similar between the PPI− and PPI+ groups. Prevotella sp and Streptococcus sp were abundant in PPI+ group. CONCLUSIONS In children with normal esophagus, PPI exposure can be associated with upregulation of esophageal mucosal homeostasis and epithelial cell function genes in a cell-type independent manner, and an altered esophageal microbiome. Additional studies are warranted to validate our findings and to investigate the causal effect of PPIs on the normal esophageal epithelium and microbial communities.