AUTHOR=Zhao Zirui , Xu Zhongye , Lv Dongming , Rong Yanchao , Hu Zhicheng , Yin Rong , Dong Yunxian , Cao Xiaoling , Tang Bing 

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

JOURNAL=Frontiers in Medicine

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1380938

DOI=10.3389/fmed.2024.1380938

ISSN=2296-858X

ABSTRACT=<sec id="sec1"><title>Objective</title><p>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.</p></sec><sec id="sec2"><title>Methods</title><p>We retrieved valid instrumental variables from the genome-wide association study (GWAS) files of the gut microbiome (<italic>n</italic> = 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.</p></sec><sec id="sec3"><title>Results</title><p>According to the inverse variance-weighted estimation, we identified that ten bacterial traits (<italic>Class Actinobacteria, Class Bacteroidia</italic>, <italic>family Bifidobacteriaceae</italic>, <italic>family Rikenellaceae</italic>, <italic>genus Lachnospiraceae (UCG004 group)</italic>, <italic>genus Ruminococcaceae (UCG013 group)</italic>, <italic>order Bacteroidales</italic>, <italic>order Bifidobacteriales</italic>, <italic>genus Peptococcus</italic> and <italic>genus Victivallis</italic>) were negatively correlated with skin fibrosis while five bacterial traits (<italic>genus Olsenella</italic>, <italic>genus Oscillospira</italic>, <italic>genus Turicibacter</italic>, <italic>genus Lachnospiraceae (NK4A136group</italic>), and <italic>genus Sellimonas</italic>) were positively correlated. No results were obtained from reverse MR analysis. No significant heterogeneity or horizontal pleiotropy was observed in MR analysis.</p></sec><sec id="sec4"><title>Objective conclusion</title><p>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.</p></sec>