Genetic evidence of bidirectional mendelian randomization study on the causality between gut microbiome and respiratory diseases contributes to gut-lung axis

Abstract Observational studies and clinical trials have suggested the relationship between the gut microbiome and respiratory diseases, but the causality between them remains unclear. Firstly, we selected eight respiratory diseases Genome-wide association study (GWAS) datasets mainly from the FinnGen collaboration as outcomes. The exposure was based on GWAS statistics about the gut microbiome, sourced from the MiBioGen consortium, including gut microbial taxa. The causal link between the gut microbiome and respiratory illnesses was then estimated using a Two-sample Mendelian randomization (MR) analysis, including the inverse-variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode. To ensure reliability, F-statistics and sensitivity tests were conducted. Furthermore, we performed a reverse MR analysis of the pre-Mendelian positive findings to possible reverse causality. For the 196 gut microbe taxa, the IVW analysis suggested 88 potential associations with eight clinically prevalent respiratory diseases. Among them, 30 causal associations were found in more than one MR method. Multiple statistical corrections have confirmed three causal associations: genus Holdemanella was a risk factor for chronic obstructive pulmonary disease (COPD) (P = 1.3 × 10−4, OR = 1.18), family FamilyXIII was a protective factor for COPD (P = 1.3 × 10−3, OR = 0.75), and genus Oxalobacter was a risk factor for asthma (P = 2.1 × 10−4, OR = 1.09). Our MR analysis results indicate that there would be a causal relationship between the gut microbiome and respiratory diseases, contributing to the gut-lung axis. This finding offers new insights into the gut microbiome’s roles in respiratory diseases’ clinical prevention, pathogenesis, and improvement of clinical symptoms. Further randomized controlled trials are necessary to clarify the protective effect of probiotics and fecal microbial transplantation on respiratory health.