Causal Relationships Between Iron Deficiency Anemia, Gut Microbiota, and Metabolites: Insights from Mendelian Randomization and In Vivo Data.

Background: Iron deficiency anemia (IDA) is a common type of anemia in children and pregnant women. The effects of iron deficiency on gut microbiota and metabolic profiles are not fully understood. Methods: Mendelian randomization (MR) analysis was conducted to explore associations among IDA, gut microbiota, and metabolites. MR analysis was conducted using computational methods, utilizing human genetic data. Data were obtained from genome-wide association studies (GWAS), with inverse-variance-weighted (IVW) as the primary method. Animal models evaluated the effects of IDA on gut microbiota and metabolic profiles. Results: IVW analysis revealed significant associations between gut microbial taxa and IDA. The genus Desulfovibrio was protective (OR = 0.85, 95% CI: 0.77-0.93, p = 0.001), while Actinomyces (OR = 1.12, 95% CI: 1.01-1.23, p = 0.025) and family XIII (OR = 1.16, 95% CI: 1.01-1.32, p = 0.035) increased IDA risk. Glycine was protective (OR = 0.95, 95% CI: 0.91-0.99, p = 0.011), whereas medium low density lipoprotein (LDL) phospholipids increased risk (OR = 1.07, 95% CI: 1.00-1.15, p = 0.040). Animal models confirmed reduced Desulfovibrio, increased Actinomyces, and altered metabolites, including amino acids and phospholipids. Conclusions: IDA significantly impacts gut microbiota and metabolic profiles, offering insights for therapeutic strategies targeting microbiota and metabolism.