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The relationship between gut microbiota, plasma metabolites, and iron deficiency anemia in European populations: a
XuWen Zheng1, WenMing Shen1, JinNan Yin1
1Emergency Department, Wujin Hospital Affiliated with Jiangsu University and Wujin Clinical College of Xuzhou Medical University, Changzhou, People's Republic of China.
Objectives:
Previous research indicates that gut microbial composition significantly affects iron metabolism and absorption, potentially influencing the risk of iron deficiency anemia (IDA). This study aimed to investigate how plasma metabolites might mediate the relationship between gut microbiota and IDA.
Methods:
We performed MR analyses utilizing publicly available genome-wide association study (GWAS) data, comprising 5,959 individuals for gut microbiota characterization and 8,299 individuals for plasma metabolite profiling. Outcome data for IDA were sourced from large-scale cohorts including Pan-UKB, FinnGen, and GERA, collectively encompassing 28,075 IDA cases and 857,930 controls. We assessed the mediating role of identified plasma metabolites on the relationship between gut microbial taxa and IDA using the product-of-coefficients method.
Results:
Our analyses identified 18 gut bacterial taxa and numerous plasma metabolites with potential causal links to IDA. For example, genetically higher abundance of species Ruminococcus E sp003521625 increased IDA risk (OR = 1.20; 95 % CI = 1.04-1.39; P = 0.011), whereas higher abundance of family Jiangellaceae decreased risk (OR = 0.77; 95 % CI = 0.61-0.98; P = 0.035). Mediation analyses revealed that the metabolite 1-palmitoyl-2-stearoyl-glycero-3-phosphocholine (PSPC) significantly mediated the Jiangellaceae - IDA association, with an indirect effect of -0.0477 (95 % CI = -0.0952 to -0.0001; P = 0.049) accounting for approximately 18.55 % of the total effect.
Conclusion:
Our findings validate the crucial role of gut microbiota in IDA etiology, highlighting mediation via key plasma metabolites. These insights enhance understanding of the gut microbiota-hematopoiesis axis and offer potential avenues for novel biomarkers or therapeutic interventions targeting IDA.
Insights
Gut microbiota impacts iron deficiency anemia (IDA) risk. Plasma metabolites mediate this link, with PSPC mediating the association between Jiangellaceae and IDA, offering potential new therapeutic targets.
Area of Science:
- Genetics and Genomics
- Microbiome Research
- Metabolomics
- Hematology
Background:
- Gut microbial composition is known to influence iron metabolism and absorption.
- This influence may play a role in the development of iron deficiency anemia (IDA).
- The specific mechanisms, particularly the role of plasma metabolites, remain underexplored.
Purpose of the Study:
- To investigate the mediating role of plasma metabolites in the relationship between gut microbiota and IDA.
- To identify specific gut microbial taxa and plasma metabolites causally linked to IDA.
- To elucidate the gut microbiota-hematopoiesis axis.
Main Methods:
- Utilized Mendelian randomization (MR) analyses on publicly available genome-wide association study (GWAS) data.
- Included large-scale cohorts for gut microbiota (n=5,959), plasma metabolites (n=8,299), and IDA outcomes (n=28,075 cases, n=857,930 controls).
- Employed the product-of-coefficients method to assess mediation by plasma metabolites.
Main Results:
- Identified 18 gut bacterial taxa and multiple plasma metabolites associated with IDA risk.
- Demonstrated that higher abundance of Ruminococcus E sp003521625 increased IDA risk, while Jiangellaceae decreased it.
- Found that 1-palmitoyl-2-stearoyl-glycero-3-phosphocholine (PSPC) significantly mediated the association between Jiangellaceae and IDA, explaining ~18.55% of the total effect.
Conclusions:
- Confirmed the significant role of gut microbiota in IDA etiology through mediation by plasma metabolites.
- Highlighted PSPC as a key mediator in the gut microbiota-IDA pathway.
- Suggests potential for novel IDA biomarkers and therapeutic interventions targeting the gut microbiota-hematopoiesis axis.
