Association of the gut microbiome and different phenotypes of COPD and asthma: a bidirectional Mendelian randomization study

Abstract

ABSTRACT Mounting evidence has revealed the association between gut microbiota and both chronic obstructive pulmonary disease (COPD) and asthma; however, the causal association between gut microbiota and specific disease phenotypes remains to be determined. This study employed bidirectional two-sample Mendelian randomization (MR) analyses to investigate the potential causal relationship between gut microbiota and these conditions. The research utilized genome-wide association study (GWAS) data from the MiBioGen consortium for gut microbiota and the integrative epidemiology unit (IEU) Open GWAS for these conditions. Four MR analysis methods were employed: the inverse variance weighted (IVW) test, MR-Egger, weighted median, and weighted mode methods. The IVW method results are considered the primary findings. Sensitivity analyses, including heterogeneity tests, horizontal pleiotropy analysis, and leave-one-out analysis, were used to enhance robustness. Our MR study identified eight gut microbiota taxa potentially associated with the risk of different types of COPD and asthma. These include two taxa for early-onset COPD: Streptococcaceae [odds ratio (OR) = 1.315, 95% confidence interval (CI) = 1.071–1.616, P = 0.009] and Holdemanella (OR = 1.199, 95% CI = 1.063–1.352, P = 0.003); three for later-onset COPD: Acidaminococcaceae (OR = 1.312, 95% CI = 1.098–1.567, P = 0.003), Holdemania (OR = 1.165, 95% CI = 1.039–1.305, P = 0.009), and Marvinbryantia (OR = 0.814, 95% CI = 0.697–0.951, P = 0.009); one for allergic asthma: Butyricimonas (OR = 0.794, 95% CI = 0.693–0.908, P = 0.001); and two for non-allergic asthma: Clostridia (OR = 1.255, 95% CI = 1.043–1.511, P = 0.016) and Clostridiales (OR = 1.256, 95% CI = 1.048–1.506, P = 0.014).IMPORTANCEIndividuals with diverse phenotypes of chronic obstructive pulmonary disease (COPD) and asthma exhibit different responses to the conventional “one treatment fits all” approach. Recent research has revealed the significant role of the gut-lung axis in both COPD and asthma. However, the specific impact of gut microbiota on different subtypes of these conditions remains poorly understood. Our study has identified eight gut microbiota that may be associated with the risk of different types of COPD and asthma. These findings provide evidence suggesting a potential causal relationship between gut microbiota and various phenotypes of COPD and asthma. This offers a new perspective on the origins of different disease phenotypes and points toward future exploration of phenotype-specific and personalized therapies.

Keywords

• Mendelian randomization
• gut microbiota
• early-onset COPD
• later-onset COPD
• allergic asthma
• non-allergic asthma