Paradoxical enrichment of Akkermansia in children with poorly controlled asthma: a longitudinal study

Gut dysbiosis is increasingly recognized as a factor in asthma pathogenesis, yet its relationship with disease severity and specific clinical phenotypes remains unclear. This longitudinal study investigated the dynamic changes in gut microbiota composition associated with asthma control and severity in children.

We identified asthmatic children and matched them with healthy controls within the prospective Taiwan Childhood Environment and Allergic Diseases Cohort Study. Phenotypic data, including childhood asthma control test (C-ACT) scores, clinical severity, serum immunoglobulin E (IgE) levels, and peak expiratory flow (PEF) rates, were collected at the time of fecal sample collection. Gut microbiota composition was assessed using 16S rRNA sequencing and compared between groups. Subgroup analyses and longitudinal paired case comparisons were conducted to track microbial shifts between exacerbation and remission phases.

A total of 173 children, including 82 children with asthma (mean age: 6.9 ± 4.1 years) and 91 age- and gender-matched healthy controls (mean age: 7.5 ± 2.6 years), were recruited. Generally, children with asthma exhibited a lower relative abundance of Akkermansia, Anaerostipes, and Escherichia compared to controls. The relative abundance of Escherichia showed a significant negative correlation with C-ACT scores (β = -0.337, p = 0.016), whereas Akkermansia exhibited a significant negative correlation with PEF (β = -0.325, p = 0.032). Notably, longitudinal paired case comparisons distinguished asthma attack from remission phases, demonstrating a paradoxical enrichment of Akkermansia during exacerbations (LDA = 3.66, p = 0.023).

In contrast to the prevailing view of Akkermansia solely as a beneficial microbe, our study identifies a specific severe asthma-associated gut profile characterized by an unexpected enrichment of Akkermansia in children with poor control. This finding suggests a complex interaction between the gut microbiome and asthma severity, potentially influenced by high-intensity corticosteroid therapy. These results challenge the one-size-fits-all probiotic approach and highlight the need for precision microbiome-based interventions considering asthma phenotypes and medication history.