A novel platform for meta-omics analysis. Pilot study on inhaled corticosteroids in asthma patients with side effects

Abstract

Abstract In this study, we sought to elucidate the microbiome-related etiologies underlying the side effects of inhaled salmeterol We collected fecal samples from 24 individuals, stratified into three cohorts: asthma patients experiencing corticosteroid-induced side effects, asthma patients devoid of such side effects, and healthy controls. These samples underwent next-generation sequencing (NGS), with data processing involving quality control, trimming, and merging of sequences. Taxonomic assignments were made using Kraken2 and Braken. The DeSEQ2 R package facilitated differential abundance analysis of microbial species. Concurrently, we employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) for metabolomic profiling, with peak detection and identification carried out via metaX software. This was supplemented by classification and functional annotation, incorporating databases such as KEGG and HMDB. Integrative analysis using Multi-Omics Factor Analysis (MOFA) and ASAR provided a holistic view on the potential microbial, genetic, and metabolite contributors to the adverse effects of inhaled corticosteroids. Subsequent analysis using Global Sensitivity Analysis-Partial Rank Correlation Coefficient (GSA-PRCC) enabled us to integrate the data into a comprehensive microbiome model. This facilitated the identification of pivotal exo-metabolites and the formulation of specialized dietary interventions aimed at ameliorating side effects. Our findings corroborate known bacteria and compounds implicated in these side effects and introduce novel targets. The proposed diets, substantiated through meta-omics analyses nd modeling, hold promise for mitigating adverse reactions. Our findings corroborate known bacteria and compounds implicated in these side effects and introduce novel targets. The proposed diets, substantiated through meta-omics analyses and modeling, hold promise for mitigating adverse reactions. Nevertheless, it is imperative to acknowledge the limitations posed by the modest sample size of 24, which may not sufficiently capture the entire spectrum of microbiome elements influencing the health of asthma patients and the manifestation of corticosteroid side effects. Further research with expanded cohorts is warranted to validate and extend our findings.