AUTHOR=Qian Xinyu , Fu Zhida , Diao Chaoyue , Zhang Wenbo , Tao Weiyu , Hu Jiaqi , Zhang Shuqing , Zhao Dongbao 

TITLE=Genetic causal relationship between gut microbiome and psoriatic arthritis: a bidirectional two-sample Mendelian randomization study

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1265786

DOI=10.3389/fmicb.2023.1265786

ISSN=1664-302X

ABSTRACT=<sec id="sec1"><title>Background</title><p>Several observational studies have suggested a potential relationship between gut microbiome and psoriatic arthritis (PsA). However, the causality of this relationship still remains unclear. We aim to explore if the specific gut microbiome is causally associated with PsA at the genetic level and offer valuable insights into the etiology of PsA.</p></sec><sec id="sec2"><title>Methods</title><p>In this study, we employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal effects of the gut microbiome on PsA. Publicly accessible genome-wide association study summary data of gut microbiome were obtained from the MiBioGen consortium (<italic>n</italic> = 14,306), while the summary statistics of psoriatic arthropathies were sourced from the FinnGen consortium R8 release data (2,776 cases and 221,323 controls). The primary analytical method employed was inverse variance weighted (IVW), complemented by supplementary methods including MR-Egger, weighted median, weighted mode, maximum likelihood, MR-PRESSO, and cML-MA. Reverse MR analysis was performed on the bacteria that were found to be causally associated with PsA in forward MR analysis. Cochran’s IVW Q statistic was utilized to assess the heterogeneity of instrumental variables among the selected single nucleotide polymorphisms.</p></sec><sec id="sec3"><title>Results</title><p>IVW estimates revealed that <italic>Ruminococcaceae_UCG-002</italic> (odds ratio (OR) = 0.792, 95% confidence interval (CI), 0.643–0.977, <italic>p</italic> = 0.029) exhibited a protective effect on PsA. Conversely, <italic>Blautia</italic> (OR = 1.362, 95% CI, 1.008–1.842, <italic>p</italic> = 0.044), <italic>Eubacterium_fissicatena_group</italic> (OR = 1.28, 95% CI, 1.075–1.524, <italic>p</italic> = 0.006), and <italic>Methanobrevibacter</italic> (OR = 1.31, 95% CI, 1.059–1.621, <italic>p</italic> = 0.013) showed a positive correlation with the risk of PsA. No significant heterogeneity, horizontal pleiotropy, or outliers were observed, and the results of the MR analysis remained unaffected by any single nucleotide polymorphisms. According to the results of reverse MR analysis, no significant causal effect of PsA was found on gut microbiome.</p></sec><sec id="sec4"><title>Conclusion</title><p>This study establishes for the first time a causal relationship between the gut microbiome and PsA, providing potential valuable strategies for the prevention and treatment of PsA. Further randomized controlled trials are urgently warranted to support the targeted protective mechanisms of probiotics on PsA.</p></sec>