Altered Gut Microbiota as a Potential Risk Factor for two types of anemia: insights from Mendelian randomization analysis

Abstract Background Numerous observational studies have indicated correlations between gut microbiota and anemia, specific causal relationships remain unclear. We investigated these relationships using Mendelian randomization (MR) analysis. Methods We acquired gut microbiota data at the multiple phylogenetic levels (five phyla, 10 classes, 13 orders, 26 families, 48 genera, and 105 species) from the Dutch Microbiome Project. We also gathered data on regarding iron deficiency anemia (IDA) and aplastic anemia (AA) from the Integrative Epidemiology Unit project. We performed MR analysis by methods including inverse variance weighting and median weighting. Next, we performed sensitivity analyses to assess pleiotropy and heterogeneity, ensuring result reliability. Finally, we used data from the MiBioGen consortium as a corroborating control. Results For IDA, we identified one class, one order, and three genera associated with decreased risk; three genera associated with increased risk. These included the genus Desulfovibrio (odds ratio [OR]: 0.86, P = 1.45×10^-2), genus Ruminococcus (OR: 0.87, P = 1.81×10^-3), species Streptococcus thermophilus (OR: 0.92, P = 2.08×10^-2), and species Sutterella wadsworthensis (OR: 1.18, P = 3.48×10^-3). For AA, one genus was associated with decreased risk; one phylum, one class, three orders, four families, and five genera were associated with increased risk. These included the genus Parasutterella (OR: 0.83, P = 2.65×10^-2), species Eubacterium hallii (OR: 1.22, P = 4.17×10^-2), genus Dorea (OR: 0.90, P = 3.46×10^-2), genus Anaerotruncus (OR: 1.32, P = 2.00×10^-2), genus Intestinibacter (OR: 1.24, P = 2.05×10^-2), and species Bilophila wadsworthia (OR: 1.30, P = 3.31×10^-2). Both types of anemia had a strong association with the order Clostridiales. The Dutch Microbiome Project results demonstrated superior efficacy, corroborated by data from the MiBioGen consortium. Conslusions Our MR analysis offers genetic insights into the associations between gut microbiota and both IDA and AA, providing new avenues for disease prevention and intervention.