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

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 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.

Dynamics of Trust and Consumption of COVID-19 Information Implicate a Mechanism for COVID-19 Vaccine and Booster Uptake.

Vaccine hesitancy remains a significant barrier to achieving herd immunity and preventing the further spread of COVID-19. Understanding contributors to vaccine hesitancy and how they change over time may improve COVID-19 mitigation strategies and public health policies. To date, no mechanism explains how trust in and consumption of different sources of information affect vaccine uptake. A total of 1594 adults enrolled in our COVID-19 testing program completed standardized surveys on demographics, vaccination status, use, reliance, and trust in sources of COVID-19 information, from September to October 2021, during the COVID-19 Delta wave. Of those, 802 individuals (50.3%) completed a follow-up survey, from January to February 2022, during the Omicron-wave. Regression analyses were performed to understand contributors to vaccine and booster uptake over time. Individuals vaccinated within two months of eligibility (early vaccinees) tended to have more years of schooling, with greater trust in and consumption of official sources of COVID-19 information, compared to those who waited 3-6 months (late vaccinees), or those who remained unvaccinated at 6 months post-eligibility (non-vaccinees). Most (70.1%) early vaccinees took the booster shot, compared to only 30.5% of late vaccinees, with the latter group gaining trust and consumption of official information after four months. These data provide the foundation for a mechanism based on the level of trust in and consumption of official information sources, where those who increased their level of trust in and consumption of official information sources were more likely to receive a booster. This study shows that social factors, including education and individual-level degree of trust in (and consumption of) sources of COVID-19 information, interact and change over time to be associated with vaccine and booster uptakes. These results are critical for the development of effective public health policies and offer insights into hesitancy over the course of the COVID-19 vaccine and booster rollout.

Opposing Role of Trust as a Modifier of COVID-19 Vaccine Uptake in an Indigenous Population.

Native Hawaiians and other Pacific Islanders (NHPIs) were disproportionately impacted by COVID-19 and remain significantly under-vaccinated against SARS-CoV-2. To understand vaccine hesitancy, we surveyed 1124 adults residing in a region with one of the lowest vaccination rates in Hawaii during our COVID-19 testing program. Probit regression analysis revealed that race/ethnicity was not directly associated with the probability of vaccine uptake. Instead, a higher degree of trust in official sources of COVID-19 information increased the probability of vaccination by 20.68%, whereas a higher trust in unofficial sources decreased the probability of vaccination by 12.49% per unit of trust. These results revealed a dual and opposing role of trust on vaccine uptake. Interestingly, NHPIs were the only racial/ethnic group to exhibit a significant positive association between trust in and consumption of unofficial sources of COVID-19 information, which explained the vaccine hesitancy observed in this indigenous population. These results offer novel insight relevant to COVID-19 mitigation efforts in minority populations.

Community-Based Participatory Research Integrates Behavioral and Biological Research to Achieve Health Equity for Native Hawaiians.

Native Hawaiians bear a disproportionate burden of type-2 diabetes and related complications compared to all other groups in Hawai'i (e.g., Whites, Japanese, Korean). Distrust in these communities is a significant barrier to participation in epigenetic research studies seeking to better understand disease processes. The purpose of this paper is to describe the community-based participatory research (CBPR) approach and research process we employed to integrate behavior and biological sciences with community health priorities. A CBPR approach was used to test a 3-month evidence-based, diabetes self-management intervention (N = 65). To investigate the molecular mechanisms linking inflammation with glucose homeostasis, a subset of participants (n = 16) provided peripheral blood mononuclear cells. Community and academic researchers collaborated on research design, assessment protocols, and participant recruitment, prioritizing participants' convenience and education and strictly limiting the use of the data collected. Preliminary results indicate significant changes in DNA methylation at gene regions associated with inflammation and diabetes signaling pathways and significant improvements in hemoglobin A1c, self-care activities, and diabetes distress and understanding. This study integrates community, behavioral, and epigenomic expertise to better understand the outcomes of a diabetes self-management intervention. Key lessons learned suggest the studies requiring biospecimen collection in indigenous populations require community trust of the researchers, mutual benefits for the community and researchers, and for the researchers to prioritize the community's needs. CBPR may be an important tool in providing communities the voice and protections to participate in studies requiring biospecimens.