Metabolites and Gut Microbiome Impact Insulin Homeostasis in ABO Blood Groups

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A variety of factors can impact disease development, including metabolites and the gut microbiome, making their inclusion in studies essential for developing a comprehensive characterization of disease etiopathogenesis, as well as viable treatments. For example, research has documented the impact of metabolites in the gut microbiome on host physiology, and has begun exploring the correlation between ABO blood groups, type 2 diabetes, and the gut microbiome.1,2 In addition, an elevated risk for type 2 diabetes, venous thrombosis, and myocardial infarction has been found in the ABO blood groups.3,4,5,6 However, only minimal research exists exploring this dynamic amongst diverse cohorts, which proves problematic as the efficacy of treatments varies for different populations.

In a study entitled, “Microbiome and Insulin Longitudinal Evaluation Study,” published in Metabolites, we observed the connection between the gut microbiome, plasma metabolites, ABO blood groups, and insulin homeostasis for type 2 diabetes in two cohorts: one comprising African Americans and the other non-Hispanic whites, with 109 and 210 respectively included in each group.7 The findings indicate that ABO haplotypes impact insulin-related traits.7

Insulin Correlation with ABO Differs Amongst Populations

In particular, the study analyzed the interactions of 21 gut bacteria and 13 plasma metabolites with insulin sensitivity. First, no correlation emerged between insulin-related traits and any haplotype in the African American cohort, though some Bacteroides species showed a connection with A2 haplotypes.7

In contrast, in the non-Hispanic white group we noted a connection between A1 and higher insulin levels but smaller lactate levels and Bacteroides massiliensis than O1 haplotypes.7 These findings flag lactate as a mediator, not Bacteroides massiliensis.7 Ultimately the data indicates that for non-Hispanic whites the A1 haplotype could drive healthy insulin sensitivity and marks lactate as a contributing factor, rather than certain gut bacteria.

Need for Future Metabolites Research with Diverse Cohorts

The results of our study add to the prior body of research documenting the correlation between insulin homeostasis and the ABO blood group, as well as identify potential molecules driving the connection. Future research can continue to build on our data to further document biological pathways in both metabolites and the gut microbiome. This study, and the intentional inclusion of diverse cohorts, marks initial research aimed at delivering results that more accurately represent global populations.

With the efficacy of treatments differing amongst demographics, studies moving forward should reflect this diversity and endeavor to enroll trials that mirror our population at large. Our findings lay the groundwork for additional analysis of metabolomics, the gut microbiome, and various disease indications in diverse populations. Finally, these findings demonstrate the power of metabolomics to better understand the complicated interactions of genetics, the gut microbiome, and disease.

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References

1. Han, S., Van Treuren, W.;,Fischer, C.R., Merrill, B.D., DeFelice, B.C., Sanchez, J.M., Higginbottom, S.K., Guthrie, L., Fall, L.A., Dodd, D., et al. A metabolomics pipeline for the mechanistic interrogation of the gut microbiome. Nature. 2021; 595, 415–420.

2. Fagherazzi, G., Gusto, G., Clavel-Chapelon, F., Balkau, B., Bonnet, F. ABO and Rhesus blood groups and risk of type 2 diabetes: Evidence from the large E3N cohort study. Diabetologia. 2015; 58, 519–522.

3. Ewald, D.R.; Sumner, S.C. Blood type biochemistry and human disease. Wiley Interdiscip Rev. Syst. Biol. Med. 2016; 8, 517–535. DOI: 10.1002/wsbm.1355

4. Groot, H.E., Villegas Sierra, L.E., Said, M.A., Lipsic, E., Karper, J.C., van der Harst, P. Genetically Determined ABO Blood Group and its Associations with Health and Disease. Arterioscler. Thromb. Vasc. Biol. 2020; 40, 830–838. DOI: 10.1161/ATVBAHA.119.313658

5. Li, S., Schooling, C.M. A phenome-wide association study of ABO blood groups. BMC Med. 2020, 18, 334. DOI: 10.1186/s12916-020-01795-4

6. Liumbruno, G.M., Franchini, M. Beyond immunohaematology: The role of the ABO blood group in human diseases. Blood Transfus. 2013; 11, 491–499.

7. Li-Gao, R., Grubbs, K., Bertoni, A.G., Hoffman, K.L., Petrosino, J.F., Ramesh, G., Wu, M., Rotter, J.I., Chen, Y-D.I., Evans, A.M., Robinson, R.J., Sommerville, L., Mook-Kanamori, D., Goodarzi, M.O., Michelotti, G.A., Sheridan, P.A.. The Roles of Gut Microbiome and Plasma Metabolites in the Associations between ABO Blood Groups and Insulin Homeostasis: The Microbiome and Insulin Longitudinal Evaluation Study (MILES). Metabolites. 2022; 12(9): 787. https://doi.org/10.3390/metabo12090787

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