The Role of Gut Microbiota in Thromboangiitis Obliterans: Cohort and Mendelian Randomization Study

Background and aims: Thromboangiitis obliterans (TAO), also known as Buerger’s disease, is a rare vasculitis. Observational epidemiology studies have suggested a relationship between the gut microbiota and TAO. However, due to confounding factors and reverse causality, the causal relationship remains unclear. Based on the assumption of their association, this study sought specific gut microbiota causally linked to TAO. Methods: The case–control study was conducted at the Xiangya Hospital of Central South University from November 2022 to January 2023 including twelve TAO patients and nine healthy controls. We conducted a Mendelian randomization (MR) study using summary statistics from a genome-wide association study (GWAS) of gut microbiota and TAO. Considering the scale and accessibility of the data, the MiBioGen consortium served as the exposure, whereas the FinnGen consortium GWAS study served as the outcome. Finally, we compared the results of the MR with those of the case–control studies. Results: The inverse variance weighted (IVW) (OR = 0.119, 95% CI: 0.021–0.688, <i>p</i> = 0.017) and maximum likelihood (ML) (OR = 0.121, 95% CI: 0.020–0.742, <i>p</i> = 0.022) estimates suggest that <i>Ruminiclostridium 5</i> has a suggestive protective effect on TAO while the IVW (OR = 5.383, 95% CI: 1.128–25.693, <i>p</i> = 0.035) and ML (OR = 5.658, 95% CI: 1.142–28.021, <i>p</i> = 0.034) estimates suggest that <i>Eubacterium</i> (<i>xylanophilum group</i>) has a suggestive risk effect on TAO, and the ML (OR = 0.055, 95% CI: 0.004–0.755, <i>p</i> = 0.030) estimates suggest that <i>Lachnospira</i> has a suggestive protective effect on TAO. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. The results of the case–control study showed that the TAO had a lower relative abundance of <i>Ruminiclostridium 5</i> (<i>p</i> = 0.015) and <i>Lachnospira</i> (<i>p</i> = 0.048), and a higher relative abundance of <i>Eubacterium</i> (<i>xylanophilum group</i>) (<i>p</i> = 0.029) than the healthy controls. These results were consistent with the MR analysis. Conclusions: Our study demonstrates that <i>Ruminiclostridium 5</i>, <i>Lachnospira</i>, and <i>Eubacterium</i> (<i>xylanophilum group</i>) are causally related to TAO, suggesting their potential significance for the prevention and treatment of TAO.