Objective: This study aimed to investigate the role of the gut microbiome in androgenetic alopecia (AGA) among obese individuals using Mendelian randomization (MR), and to identify potential therapeutic targets for mitigating AGA in this population. Methods: Genomic data for 412 gut microbiomes, AGA, and obesity were obtained from genome-wide association studies (GWAS). Bidirectional MR was performed using inverse variance weighted (IVW) as the primary analysis method, complemented by sensitivity analyses. Potential therapeutic targets within the gut microbiome associated with AGA in obese individuals were identified. Results: Two gut microbiomes were identified as having a significant impact on obese individuals with AGA. Specifically, the abundance of the sulfoglycolysis pathway in gut bacteria was found to significantly increase the risk of both obesity and AGA. In contrast, the abundance of the de novo biosynthesis of the adenosine ribonucleotide pathway in gut bacteria was associated with a significant increase in the risk of obesity but a significant decrease in the risk of AGA. Conclusions: The abundance of gut bacterial pathways, including sulfoglycolysis and the de novo biosynthesis of adenosine ribonucleotides, can serve as potential therapeutic targets for managing obesity-associated AGA. These findings offer a novel research direction for the development of innovative diagnostic and treatment strategies for patients with obesity and AGA.

To explore the associations between protein-level ratios (rQLTs) and duodenal ulcer (DU) risk using Mendelian randomization (MR), colocalization, and pathway analysis approaches. A bidirectional MR approach was used to identify molecular targets linking rQLTs with DU, employing the inverse variance weighted (IVW) method for causal estimation. Colocalization analysis ensured the reliability of inferred causal relationships. Gene interaction networks were constructed via STRING, and key regulatory hub-genes were identified through Cytoscape analysis. Significant inverse associations were found between rQLT-ACE2/GGT1 (Angiotensin-converting enzyme 2/γ-glutamyl transpeptidase 1) (IVW, OR (95% CI) = 0.754 (0.674–0.843), adjusted P_IVW = 0.0005), and DU risk in the East Asian (Japanese) population. No statistically significant associations were observed in the European population. The findings indicate a genetic inverse association between rQLT-ACE2/GGT1 and DU risk in the East Asian (Japanese) population, while no corresponding association was observed in Europeans. These results provide genetic evidence consistent with a potential association rather than causal inference or biomarker validation. This study does not support conclusions regarding diagnostic or therapeutic utility at this stage.