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)
Ruifang Li-Gao,
Kirk Grubbs,
Alain G. Bertoni,
Kristi L. Hoffman,
Joseph F. Petrosino,
Gautam Ramesh,
Martin Wu,
Jerome I. Rotter,
Yii-Der Ida Chen,
Anne M. Evans,
Richard J. Robinson,
Laura Sommerville,
Dennis Mook-Kanamori,
Mark O. Goodarzi,
Gregory A. Michelotti,
Patricia A. Sheridan
Affiliations
Ruifang Li-Gao
Department of Clinical Epidemiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Kirk Grubbs
Metabolon, Inc., Morrisville, NC 27560, USA
Alain G. Bertoni
Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA
Kristi L. Hoffman
Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
Joseph F. Petrosino
Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
Gautam Ramesh
School of Medicine, University of California San Diego, La Jolla, CA 92161, USA
Martin Wu
Department of Biology, University of Virginia, Charlottesville, VA 22904, USA
Jerome I. Rotter
The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA
Yii-Der Ida Chen
The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA
Anne M. Evans
Metabolon, Inc., Morrisville, NC 27560, USA
Richard J. Robinson
Metabolon, Inc., Morrisville, NC 27560, USA
Laura Sommerville
Metabolon, Inc., Morrisville, NC 27560, USA
Dennis Mook-Kanamori
Department of Clinical Epidemiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Mark O. Goodarzi
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Non-O blood groups are associated with decreased insulin sensitivity and risk of type 2 diabetes. A recent study pinpointed the associations between ABO blood groups and gut microbiome, which may serve as potential mediators for the observed increased disease risks. We aimed to characterize associations between ABO haplotypes and insulin-related traits as well as potential mediating pathways. We assessed insulin homeostasis in African Americans (AAs; n = 109) and non-Hispanic whites (n = 210) from the Microbiome and Insulin Longitudinal Evaluation Study. The ABO haplotype was determined by six SNPs located in the ABO gene. Based on prior knowledge, we included 21 gut bacteria and 13 plasma metabolites for mediation analysis. In the white study cohort (60 ± 9 years, 42% male), compared to the O1 haplotype, A1 was associated with a higher Matsuda insulin sensitivity index, while a lower relative abundance of Bacteroides massiliensis and lactate levels. Lactate was a likely mediator of this association but not Bacteroides massiliensis. In the AAs group (57 ± 8 years, 33% male), we found no association between any haplotype and insulin-related traits. In conclusion, the A1 haplotype may promote healthy insulin sensitivity in non-Hispanic whites and lactate likely play a role in this process but not selected gut bacteria.
