Contact us Demo our platform

Blog

Metabolites and Gut Microbiome Impact Insulin Homeostasis in ABO Blood Groups

Metabolites-and-Gut-Microbiome-Impact-Insulin-Homeostasis-in-ABO-Blood-Groups

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.

Ready to see what new insights metabolomics can help your research reveal?
Contact us today to discuss your project or study.

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

Metabolon
Our team is made up of over 45 PhDs, has been published 4,000+ times, and is committed to hard work, excellence, and success through collaboration. With over 15,000 projects, Metabolon has been a trusted partner of researchers for over 25 years.

Topics

Diabetes | Microbiome

Share this article

Related Blog Posts

See All Blog Posts

GET STARTED

Talk with an expert

Request a quote, get detailed information on sample types, or learn how metabolomics can accelerate your research. Find our contact details are here.

Find us on:

Talk with a Metabolomics expert

✕

References

1. Zgoda-Pols, J.R., et al., Metabolomics analysis reveals elevation of 3-indoxyl sulfate in plasma and brain during chemically-induced acute kidney injury in mice: investigation of nicotinic acid receptor agonists. Toxicol Appl Pharmacol, 2011. 255(1): p. 48-56.

2. Bryant, J.A., et al., The impact of an oral purified microbiome therapeutic on the gastrointestinal microbiome. Nat Med, 2026. 32(1): p. 186-196

3. McGovern, B .H., et al., SER-109, an Investigational Microbiome Drugto Reduce Recurrence After Clostridioides difficile Infection: Lessons Learned From a Phase 2 Trial. Clin Infect Dis, 2021. 72(12): p. 2132-2140.

4. Feuerstadt, P., et al., SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection. N Engl J Med, 2022. 386(3): p. 220-229.

5. Hu, Z., et al., Targeted metabolomics reveals novel diagnostic biomarkers for colorectal cancer. Mol Oncol, 2025. 19(6): p. 1737-1750.

6. Butler, F.M., et al., Vegetarian Dietary Patterns and Diet-Related Metabolites Are Associated With Kidney Function in the Adventist Health Study-2 Cohort. J Ren Nutr, 2025.

7. Stanford, J., et al., Metabolomic Profiling and Diet Quality Scoring in a Randomized Crossover Trial of Healthy and Typical Dietary Patterns. Mol Nutr Food Res, 2025 . 69(23): p. e70271.

8. O’Connor, L.E., et al., Metabolomic Profiling of an Ultraprocessed Dietary Pattern in a Domiciled Randomized Controlled Crossover Feeding Trial. J Nutr, 2023. 153(8): p. 2181-2192.

9. Fritsch, D.A., et al., Microbiome function underpins the efficacy of a fiber-supplemented dietary intervention in dogs with chronic large bowel diarrhea. BMC Vet Res, 2022. 18(1): p. 245.

10. Leal, L.N., et al., Preweaning nutrient supply improves lactation productivity and reduces the risk of culling in Holstein cows. J Dairy Sci, 2025. 108(6): p. 5875-5888.

11. Ahsin, M., et al., Soil and pasture health underlie improved beef nutrient density determined by untargeted metabolomics in Southern US grass finished beef systems. NPJ Sci Food, 2025. 9(1): p. 151.

12. Yin, W., et al., Plasma lipid profiling across species for the identification of optimal animal models of human dyslipidemia. J Lipid Res, 2012. 53(1): p. 51-65.

13. Porter, F .D., et al., Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease. Sci Transl Med, 2010. 2(56): p. 56ra81.

14. Needham, B .D., et al., Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder. Biol Psychiatry, 2021. 89(5): p. 451-462

15. Li, C., et al., Estradiol and mTORC2 cooperate to enhance prostaglandin biosynthesis and tumorigenesis in TSC2-deficient LAM cells. J Exp Med, 2014. 211(1): p. 15-28.

16. Green, P.G., et al., Metabolic flexibility and reverse remodelling of the failing human heart. Eur Heart J, 2025. 46(25): p. 2422-2433.

17. Maekawa, H., et al., SGLT2 inhibition protects kidney function by SAM-dependent epigenetic repression of inflammatory genes under metabolic stress. J Clin Invest, 2025. 135(19).

18. Wu, D., et al., Integrated screens reveal that guanine nucleotide depletion, which is irreversible via targeting IMPDH2, inhibits pancreatic cancer and potentiates KRAS inhibition. Gut, 2026.

19. Schwerdtfeger, L.A., et al., Gut microbiota and metabolites are linked to disease progression in multiple sclerosis. Cell Rep Med, 2025. 6(4): p. 102055.

20. Wu, H., et al., Microbiome-metabolome dynamics associated with impaired glucose control and responses to lifestyle changes. Nat Med, 2025. 31(7): p. 2222-2231.

21. Jacobs, J.P., et al., Cognitive behavioral therapy for irritable bowel syndrome induces bidirectional alterations in the brain-gut-microbiome axis associated with gastrointestinal symptom improvement. Microbiome, 2021. 9(1): p. 236.

22. Pietzner, M., et al., Plasma metabolites to profile pathways in noncommunicable disease multimorbidity. Nat Med, 2021. 27(3): p. 471-479.

23. Faquih, T.O., et al., Robust Metabolomic Age Prediction Based on a Wide Selection of Metabolites. J Gerontol A Biol Sci Med Sci, 2025. 80(3).

24. Scherer, N., et al., Coupling metabolomics and exome sequencing reveals graded effects of rare damaging heterozygous variants on gene function and human traits. Nat Genet, 2025. 57(1): p. 193-205.

25. Holmes, Z.C., et al., Untargeted metabolomic analysis of human milk from healthy mothers reveals drivers of metabolite variability. Sci Rep, 2024. 14(1): p. 20827.

26. Titz, B., et al., Implications of Ocular Confounding Factors for Aqueous Humor Proteomic and Metabolomic Analyses in Retinal Diseases. Transl Vis Sci Technol, 2024. 13(6): p. 17.

27. Bloom, S.M., et al., Cysteine dependence of Lactobacillus iners is a potential therapeutic target for vaginal microbiota modulation. Nat Microbiol, 2022. 7(3): p. 434-450.

28. Leimer, E.M., et al., Lipid profile of human synovial fluid following intra-articular ankle fracture. J Orthop Res, 2017. 35(3): p. 657-666.