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

miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells

Glioblastoma multiforme (GBM) is an invariably fatal central nervous system tumor despite treatment with surgery, radiation, and chemotherapy. Further insights into the molecular and cellular mechanisms that drive GBM formation are required to improve patient outcome. MicroRNAs are emerging as important regulators of cellular differentiation and proliferation, and have been implicated in the etiology of a variety of cancers, yet the role of microRNAs in GBM remains poorly understood. In this study, we investigated the role of microRNAs in regulating the differentiation and proliferation of neural stem cells and glioblastoma-multiforme tumor cells.status: publishe

The Effects of COVID-19 Vaccine Mandates in Hawaii

Having been affected by the highest increase in COVID-19 cases since the start of the pandemic, Honolulu and Maui counties in Hawaii implemented vaccine passport mandates for select industries in September 2021. However, the degree to which such mandates impacted COVID-19 mitigation efforts and economics remains poorly understood. Herein, we describe the effects of these mandates on changes in three areas using difference-in-difference regression models: (1) business foot traffic; (2) number of COVID-19 cases per 100,000 individuals, and (3) COVID-19 vaccination rates across counties affected or unaffected by the mandates. We observed that although businesses affected by mandates experienced a 6.7% decrease in foot traffic over the 14 weeks after the mandates were implemented, the number of COVID-19 cases decreased by 19.0%. Notably, the vaccination rate increased by 1.41% in counties that implemented mandates. In addition, towards the end of the studied period, the level of foot traffic at impacted businesses converged towards the level of that of non-impacted businesses. As such, the trade-off in temporary losses at businesses was met with significant gains in public health and safety

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

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

Awakening: The Unveiling of Historically Unaddressed Social Inequities During the COVID-19 Pandemic in the United States

The violence and victimization brought by colonization and slavery and justified for over a century by race-based science have resulted in enduring inequities for black, Indigenous and people of color (BIPOC) across the United States. This is particularly true if BIPOC individuals have other intersecting devalued identities. We highlight how such longstanding inequities paved the way for the disproportionate burdens of coronavirus disease 2019 (COVID-19) among the BIPOC populations across the country and provide recommendations on how to improve COVID-19 mitigation strategies with the goal of eliminating disparities

Immuno-Microbial Signature of Vaccine-Induced Immunity against SARS-CoV-2

Although vaccines address critical public health needs, inter-individual differences in responses are not always considered in their development. Understanding the underlying basis for these differences is needed to optimize vaccine effectiveness and ultimately improve disease control. In this pilot study, pre- and post-antiviral immunological and gut microbiota features were characterized to examine inter-individual differences in SARS-CoV-2 mRNA vaccine response. Blood and stool samples were collected before administration of the vaccine and at 2-to-4-week intervals after the first dose. A cohort of 14 adults was separated post hoc into two groups based on neutralizing antibody levels (high [HN] or low [LN]) at 10 weeks following vaccination. Bivariate correlation analysis was performed to examine associations between gut microbiota, inflammation, and neutralization capacity at that timepoint. These analyses revealed significant differences in gut microbiome composition and inflammation states pre-vaccination, which predicted later viral neutralization capacity, with certain bacterial taxa, such as those in the genus Prevotella, found at higher abundance in the LN vs HN group that were also negatively correlated with a panel of inflammatory factors such as IL-17, yet positively correlated with plasma levels of the high mobility group box 1 (HMGB-1) protein at pre-vaccination. In particular, we observed a significant inverse relationship (Pearson = −0.54, p = 0.03) between HMGB-1 pre-vaccination and neutralization capacity at 10 weeks post-vaccination. Consistent with known roles as mediators of inflammation, our results altogether implicate HMGB-1 and related gut microbial signatures as potential biomarkers in predicting SARS-CoV-2 mRNA vaccine effectiveness measured by the production of viral neutralization antibodies