Background There is increasing interest about the interplay between host genetics and gut microbiome on human complex diseases, with prior evidence mainly derived from animal models. In addition, the shared and distinct microbiome features among human complex diseases remain largely unclear.
Results The analysis was based on a Chinese population with 1,475 participants. We estimated the SNP-based heritability, which suggested that Desulfovibrionaceae and Odoribacter had significant heritability estimates (0.456 and 0.476, respectively). We performed a microbiome genome-wide association study to identify host genetic variants associated with gut microbiome.We then conducted bi-directional Mendelian randomization analyses to examine the potential causal associations between gut microbiome and human complex diseases. We found that Saccharibacteria (per 1-SD higher in the log-transformed abundance) could potentially decrease the concentration of serum creatinine (Beta: -0.011 [95%CI: -0.019, -0.003], p=0.007) and increase estimated glomerular filtration rate (Beta: 0.012 [95%CI: 0.004, 0.020], p=0.003). On the other hand, atrial fibrillation, chronic kidney disease and prostate cancer, as predicted by the host genetics, had potential causal effect on the abundance of some specific gut microbiota. For example, atrial fibrillation (per log odds) could increase the abundance of Burkholderiales (Beta: 0.079[95%CI: 0.009, 0.150], p=0.027) and Alcaligenaceae (Beta: 0.082[95%CI: 0.012, 0.152], p=0.022), and decrease the abundance of Lachnobacterium (Beta:-0.078[95%CI: -0.148, -0.006], p=0.034), Bacteroides coprophilus (Beta: -0.113[95%CI: -0.184, -0.041], p=0.002), Barnesiellaceae (odds ratio: 0.818[95%CI: 0.686, 0.976], p=0.026), Veillonellaceae undefined (odds ratio: 0.801[95%CI: 0.669, 0.960], p=0.017) as well as Mitsuokella (odds ratio: 0.657[95%CI: 0.496, 0.870], p=0.003). Further disease-microbiome feature analysis suggested that systemic lupus erythematosus and chronic myeloid leukemia shared common gut microbiome features.
Conclusions These results suggest that different human complex diseases share common and distinct gut microbiome features, which may help re-shape our understanding about the disease etiology in humans.