Abstract
Previous studies have suggested a link between gut microbiota and iron-deficiency anemia (IDA). However, interpreting these findings is difficult due to various factors that influence microbiome composition and the limitations of observational studies, such as confounding variables and reverse causation. This study aims to explore the causal relationship between gut microbiota and IDA using Mendelian randomization (MR) to overcome these limitations. We conducted a 2-sample MR analysis using data from genome-wide association studies from the MiBioGen Consortium and the UK Biobank. The gut microbiome data included 211 genus-level microbes linked to single-nucleotide polymorphisms from 18,340 participants in the MiBioGen Consortium. The outcome data for IDA were obtained from 484,598 participants in the UK Biobank, with 2941 cases and 481,657 controls. We assessed causal relationships using various MR techniques, primarily inverse variance weighting, and performed sensitivity analyses to confirm the robustness of our results. Nine genus-level gut microbes were significantly associated with IDA (P < .05). Protective factors included Clostridia, Actinomycetaceae, Pasteurellaceae, Oscillospira, Prevotella, and Roseburia, while risk factors included Ruminococcus gnavus group, Hungatella, and Parasutterella. Sensitivity analyses showed the reliability of these findings without significant variability. This study provides evidence for a causal relationship between specific gut bacteria and IDA risk, identifying potential targets for therapies aimed at improving outcomes for those with IDA. Further research is needed to clarify the bacteria involved.