A multi-omic analysis reveals the esophageal dysbiosis as the predominant trait of eosinophilic esophagitis

Abstract

Background Eosinophilic esophagitis (EoE) is a chronic immune-mediated rare disease, characterized by esophageal dysfunctions. It is likely to be primarily activated by food antigens and is classified as a chronic disease for most patients. Therefore, a deeper understanding of the pathogenetic mechanisms underlying EoE is needed to implement and improve therapeutic lines of intervention and ameliorate overall patient wellness. Methods RNA-seq data of 18 different studies on EoE, downloaded from NCBI GEO with faster-qdump (https://github.com/ncbi/sra-tools), were batch-corrected and analyzed for transcriptomics and metatranscriptomics profiling as well as biological process functional enrichment. The EoE TaMMA web app was designed with plotly and dash. Tabula Sapiens raw data were downloaded from the UCSC Cell Browser. Esophageal single-cell raw data analysis was performed within the Automated Single-cell Analysis Pipeline. Single-cell data-driven bulk RNA-seq data deconvolution was performed with MuSiC and CIBERSORTx. Multi-omics integration was performed with MOFA. Results The EoE TaMMA framework pointed out disease-specific molecular signatures, confirming its reliability in reanalyzing transcriptomic data, and providing new EoE-specific molecular markers including CXCL14, distinguishing EoE from gastroesophageal reflux disorder. EoE TaMMA also revealed microbiota dysbiosis as a predominant characteristic of EoE pathogenesis. Finally, the multi-omics analysis highlighted the presence of defined classes of microbial entities in subsets of patients that may participate in inducing the antigen-mediated response typical of EoE pathogenesis. Conclusions Our study showed that the complex EoE molecular network may be unraveled through advanced bioinformatics, integrating different components of the disease process into an omics-based network approach. This may implement EoE management and treatment in the coming years.

Causal relationship between eosinophilic esophagitis and inflammatory bowel disease: a bidirectional two-sample Mendelian randomization study

“…Elevated interleukin-13 in both diseases downregulate proteins associated with barrier function (desmoglein-1 and filaggrin) and altered epithelial permeability in the GI tract ( 31 – 33 ), permitting interactions between risk environmental factors (food antigens, microbial dysbiosis, antibiotic use, etc.) and the esophageal/intestinal immune system ( 28 , 34 , 35 ). Aberrant immune responses against these antigens provoke mucosal inflammation and cause diseases.…”

Microbiota profiling in esophageal diseases: Novel insights into molecular staining and clinical outcomes

“…Considering the huge effort made and the valuable resource these differentiated data may represent, the possibility of combining them in one single analysis would be key to increasing data significance and relevance and, last but not least, the sample sizes. One of the methods to combine data coming from different sources is batch correction before the comprehensive analysis, as recently shown [18] , [19] , [40] ( Fig. 3 ).…”

“…In this context, technological advancements made by high-throughput microbial RNA and DNA sequencing techniques have revolutionized gut microbiota analysis, increasing the quantity and the quality of data, abating costs, and maximizing research efforts [17] . Interesting insights on relationships between esophageal microbiome and inflammatory or neurodegenerative esophageal conditions like Eosinophilic Esophagitis (EoE) and achalasia have been recently arisen [18] . Together with advanced sequencing techniques, computational biology and informatics knowledge has spread in recent years improving efforts and reducing time and costs in microbiota study and shaping [19] .…”

Gastroparesis: The Complex Interplay with Microbiota and the Role of Exogenous Infections in the Pathogenesis of the Disease

“…For example, the Microorganisms 2023, 11, 1122 2 of 19 normal gut microbiome imparts specific functions in host nutrient metabolism, xenobiotic and drug metabolism, the maintenance of the structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens [8]. Therefore, an imbalance of the gut microbiome due to the use of antibiotics or bacterial translocation can lead to the development of diseases [7,9].…”