Identification of two distinct microbial enterophenotypes in children with moderate-to-severe asthma: results from the SysPharmPediA study

Introduction: Asthma is a heterogeneous chronic disease that presents with multiple clinical phenotypes. It has been reported that asthmatics have gut microbial imbalances that could be linked to the immune homeostasis (Abdel-Aziz et al. Clin Exp Allergy 2019; 49(8):1067-86). This study aims to identify phenotypes in asthmatic children using the gut microbial profiles. Methods: Clinical data, lung function, blood and faeces samples were collected from the Systems Pharmacology approach to uncontrolled Pediatric Asthma (SysPharmPediA) study including moderate-to-severe asthmatics aged 6-18 years and treated on GINA step ≥3. Gut microbiome 16S rRNA sequencing was performed and a clustering strategy was applied as described previously (Abdel-Aziz et al. JACI 2021; 147(1):123-34). Results: Cluster-based gut microbiome analysis of 103 asthmatic children (median age: 11.5 years, 64% male) revealed two clusters (enterotypes). They were either Bacteroides- or Prevotella-genera dominant and significantly differed in: z-scored BMI, physician-reported diagnosis of eczema and food allergy, history of severe asthma attacks and asthma-related hospital admissions within the previous year. The Prevotella dominant enterotype displayed a type-2 inflammatory phenotype, characterized by increased eosinophil (i.e. ≥0.5x109/L) and basophil counts (all p-values <0.05). Conclusion: In our study of children with moderate-to-severe asthma, two distinct enterophenotypes correlating with clinical characteristics are present. Further research should assess if signatures in the gut microbiome could become a suitable precision medicine approach for diagnostics and treatment of asthma.