PMID- 37152987 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230804 IS - 1664-8021 (Print) IS - 1664-8021 (Electronic) IS - 1664-8021 (Linking) VI - 14 DP - 2023 TI - Examining the immunoepigenetic-gut microbiome axis in the context of self-esteem among Native Hawaiians and other Pacific Islanders. PG - 1125217 LID - 10.3389/fgene.2023.1125217 [doi] LID - 1125217 AB - 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-alpha (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 differences in the immunoepigenetic-gut microbiome axis with respect to SE, warranting further investigation into its relationship to brain activity and mental health in NHPI. Unexpected results from Epi-Age analyses warrant further investigation into the relationship between biological age and disparate health outcomes among the NHPI population. The modifiable component of epigenetic processes and the gut microbiome makes this axis an attractive target for potential therapeutics, biomarker discovery, and novel prevention strategies. CI - Copyright (c) 2023 Becerra, Wells, Kunihiro, Lee, Umeda, Allan, Rubas, McCracken, Nunokawa, Lee, Pidlaoan, Phankitnirondorn, Dye, Yamamoto, Peres, Juarez and Maunakea. FAU - Becerra, Celyna Y AU - Becerra CY AD - Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, Honolulu, HI, United States. AD - IDeA Networks of Biomedical Research Excellence (INBRE), University of Hawaii at Manoa, Honolulu, HI, United States. FAU - Wells, Riley K AU - Wells RK AD - Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, Honolulu, HI, United States. AD - Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, Honolulu, HI, United States. FAU - Kunihiro, Braden P AU - Kunihiro BP AD - Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, Honolulu, HI, United States. AD - IDeA Networks of Biomedical Research Excellence (INBRE), University of Hawaii at Manoa, Honolulu, HI, United States. FAU - Lee, Rosa H AU - Lee RH AD - Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, Honolulu, HI, United States. FAU - Umeda, Lesley AU - Umeda L AD - Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, Honolulu, HI, United States. AD - Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, Honolulu, HI, United States. FAU - Allan, Nina P AU - Allan NP AD - Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, Honolulu, HI, United States. FAU - Rubas, Noelle C AU - Rubas NC AD - Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, Honolulu, HI, United States. FAU - McCracken, Trevor A AU - McCracken TA AD - Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, Honolulu, HI, United States. FAU - Nunokawa, Chandler K L AU - Nunokawa CKL AD - Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, Honolulu, HI, United States. FAU - Lee, Ming-Hao AU - Lee MH AD - Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, Honolulu, HI, United States. FAU - Pidlaoan, Felix Gerard S AU - Pidlaoan FGS AD - Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, Honolulu, HI, United States. FAU - Phankitnirondorn, Krit AU - Phankitnirondorn K AD - Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, Honolulu, HI, United States. FAU - Dye, Christian K AU - Dye CK AD - Department of Environmental Health Sciences, Columbia University Irving Medical Center, NY, NY, United States. FAU - Yamamoto, Brennan Y AU - Yamamoto BY AD - Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, Honolulu, HI, United States. FAU - Peres, Rafael AU - Peres R AD - Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, Honolulu, HI, United States. FAU - Juarez, Ruben AU - Juarez R AD - Department of Economics, University of Hawaii at Manoa, Honolulu, HI, United States. AD - University of Hawaii Economic Research Organization (UHERO), University of Hawaii at Manoa, Honolulu, HI, United States. FAU - Maunakea, Alika K AU - Maunakea AK AD - Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, Honolulu, HI, United States. LA - eng SI - figshare/10.6084/m9.figshare.21809838.v1 GR - R01 MD016593/MD/NIMHD NIH HHS/United States GR - R56 MD014630/MD/NIMHD NIH HHS/United States PT - Journal Article DEP - 20230419 PL - Switzerland TA - Front Genet JT - Frontiers in genetics JID - 101560621 PMC - PMC10154580 OTO - NOTNLM OT - DNA methylation OT - Native Hawaiians and other Pacific Islanders OT - depressive symptoms OT - epigenetic aging OT - gut microbiome OT - health disparities OT - immune system OT - self-esteem COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/05/08 06:42 MHDA- 2023/05/08 06:43 PMCR- 2023/04/19 CRDT- 2023/05/08 04:10 PHST- 2022/12/16 00:00 [received] PHST- 2023/03/21 00:00 [accepted] PHST- 2023/05/08 06:43 [medline] PHST- 2023/05/08 06:42 [pubmed] PHST- 2023/05/08 04:10 [entrez] PHST- 2023/04/19 00:00 [pmc-release] AID - 1125217 [pii] AID - 10.3389/fgene.2023.1125217 [doi] PST - epublish SO - Front Genet. 2023 Apr 19;14:1125217. doi: 10.3389/fgene.2023.1125217. eCollection 2023.