Impact of the gut microbiome on skin fibrosis: a Mendelian randomization study

Objective Skin fibrosis is a lesion in the dermis causing to itching, pain, and psychological stress. The gut microbiome plays as an essential role in skin diseases developments. We conducted a Mendelian randomization study to determine the causal association between the gut microbiome and skin fibrosis. Methods We retrieved valid instrumental variables from the genome-wide association study (GWAS) files of the gut microbiome ( n = 18,340) conducted by the MiBioGen consortium. Skin fibrosis-associated data were downloaded from the GWAS Catalog. Subsequently, a two-sample Mendelian randomization (MR) analysis was performed to determine whether the gut microbiome was related to skin fibrosis. A reverse MR analysis was also performed on the bacterial traits which were causally associated with skin fibrosis in the forward MR analysis. In addition, we performed an MR-Pleiotropy Residual Sum and Outlier analysis to remove outliers and a sensitivity analysis to verify our results. Results According to the inverse variance-weighted estimation, we identified that ten bacterial traits ( Class Actinobacteria, Class Bacteroidia , family Bifidobacteriaceae , family Rikenellaceae , genus Lachnospiraceae (UCG004 group) , genus Ruminococcaceae (UCG013 group) , order Bacteroidales , order Bifidobacteriales , genus Peptococcus and genus Victivallis ) were negatively correlated with skin fibrosis while five bacterial traits ( genus Olsenella , genus Oscillospira , genus Turicibacter , genus Lachnospiraceae (NK4A136group ), and genus Sellimonas ) were positively correlated. No results were obtained from reverse MR analysis. No significant heterogeneity or horizontal pleiotropy was observed in MR analysis. Objective conclusion There is a causal association between the gut microbiome and skin fibrosis, indicating the existence of a gut-skin axis. This provides a new breakthrough point for mechanistic and clinical studies of skin fibrosis.