Basal metabolic rate mediates the causal relationship between gut microbiota and osteoarthritis: a two-step bidirectional Mendelian randomization study

• Published in: Frontiers in microbiology Vol. 15; p. 1371679
• Main Authors: Li, Jiachen, Liang, Jianhui, Liu, Yang, Sun, Weichao, Sun, Wei
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 01.10.2024
• Subjects: basal metabolic rate; gut microbiota; mediation; Mendelian randomization; Microbiology; osteoarthritis; basal metabolic rate; Mendelian randomization; mediation; osteoarthritis; gut microbiota
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2024.1371679

The relationship between gut microbiota and osteoarthritis (OA) occurrence remains unclear. Existing research needs to clearly understand how basal metabolic rate (BMR) regulates this relationship. Therefore, using a two-step bidirectional Mendelian Randomization approach, our study aims to investigate whether BMR levels mediate the causal relationship between gut microbiota and OA. In this study, we examined publicly available summary statistics from Genome-Wide Association Studies (GWAS) to determine the correlation between gut microbiota and OA. The analysis included one primary dataset and two secondary datasets. Initially, a two-step, two-sample, and reverse MR analysis was performed to identify the causal relationship between gut microbiota and OA. Subsequently, a two-step MR analysis revealed that the relationship between microbiota and OA is mediated by BMR. Sensitivity analyses confirmed the robustness of the study results. In our analysis of the primary dataset, we discovered a positive correlation between three taxa and the outcome of OA, and eight taxa exhibited a negative correlation with the OA outcome. Through comparisons with the secondary dataset and multiple testing corrections, we found a negative association between the class (OR=0.992886277, -value = 0.003) and the likelihood of OA occurrence. Notably, knee osteoarthritis (KOA) and hip osteoarthritis (HOA) had a strong negative correlation (OR = 0.927237553/0.892581219). Our analysis suggests that BMR significantly mediates the causal pathway from to OA, with a mediated effect of 2.59%. Additionally, BMR mediates 3.98% of the impact in the path from the order and the family to OA. Besides these findings, our reverse analysis did not indicate any significant effect of OA on gut microbiota or BMR. Our research results indicate that an increase in the abundance of specific gut microbial taxa is associated with a reduced incidence of OA, and BMR levels mediate this causal relationship. Further large-scale randomized controlled trials are necessary to validate the causal impact of gut microbiota on the risk of OA. This study provides new insights into the potential prevention of OA by modulating the gut microbiota.