Examining the immunoepigenetic-gut microbiome axis in the context of self-esteem among Native Hawaiians and other Pacific Islanders

• Published in: Frontiers in Genetics
• Main Authors: Celyna Y. Becerra, Riley K. Wells, Braden P. Kunihiro, Rosa H. Lee, Lesley Umeda, Nina P. Allan, Noelle C. Rubas, Trevor A. McCracken, Chandler K. L. Nunokawa, Ming-Hao Lee, Felix Gerard S. Pidlaoan, Krit Phankitnirondorn, Christian K. Dye, Brennan Y Yamamoto, Rafael Peres, Ruben Juarez, Alika K. Maunakea
• Format: Article in Journal/Newspaper
• Language: English
• Published: Frontiers Media S.A. 2023
• Subjects: health disparities; depressive symptoms; epigenetic aging; self-esteem; immune system; gut microbiome; Genetics; QH426-470; Horvath; Pacific; DML
• Online Access: https://doi.org/10.3389/fgene.2023.1125217; https://doaj.org/article/3b6aa1db38e44054950b7776d690c5cc

Introduction: Native Hawaiian and other Pacific Islander (NHPI) populations experience higher rates of immunometabolic diseases compared to other racial-ethnic groups in Hawaii. As annual NHPI mortality rates for suicide and type 2 diabetes mellitus (T2DM) exceed those of the state as a whole, understanding the social and biological mechanisms underlying these disparities are urgently needed to enable preventive strategies.Methods: A community-based approach was used to investigate the immunoepigenetic-gut microbiome axis in an NHPI-enriched cohort of Oahu residents (N = 68). Self-esteem (SE) data was collected using a modified Rosenberg self-esteem (SE) assessment as a proxy measure for mental wellbeing in consideration for cultural competency. T2DM status was evaluated using point-of-care A1c (%) tests. Stool samples were collected for 16s-based metagenomic sequencing analyses. Plasma from blood samples were isolated by density-gradient centrifugation. Peripheral blood mononuclear cells (PBMCs) were collected from the same samples and enriched for monocytes using negative selection techniques. Flow-cytometry was used for immunoprofiling assays. Monocyte DNA was extracted for Illumina EPIC array-based methylation analysis.Results: Compared to individuals with normal SE (NSE), those with low SE (LSE) exhibited significantly higher plasma concentrations (pg/ml) of proinflammatory cytokines IL-8 (p = 0.051) and TNF-α (p = 0.011). Metagenomic analysis revealed that the relative abundance (%) of specific gut bacteria significantly differed between SE groups - some of which directly correlated with SE scores. Gene ontology analysis revealed that 104 significantly differentially methylated loci (DML) between SE groups were preferentially located at genes involved in immunometabolic processes. Horvath clock analyses indicated epigenetic age (Epi-Age) deceleration in individuals with LSE and acceleration in individuals with NSE (p = 0.042), yet was not reproduced by other clocks.Discussion: These data reveal novel ...