Medical School Hotline: Immunoepigenetic-Microbiome Axis: Implications for Health Disparities Research in Native Hawaiians and Pacific Islanders

Abstract

Native Hawaiian and Pacific Islander (NHPI) populations suffer from disproportionately higher rates of chronic conditions, such as type 2 diabetes, that arises from metabolic dysfunction and are often associated with obesity and inflammation. In addition, the global coronavirus disease 2019 pandemic has further compounded the effect of health inequities observed in Indigenous populations, including NHPI communities. Reversible lifestyle habits, such as diet, may either be protective of or contribute to the increasing prevalence of health inequities in these populations via the immunoepigenetic-microbiome axis. This axis offers insight into the connection between diet, epigenetics, the microbiome composition, immune function, and response to viral infection. Epigenetic mechanisms that regulate inflammatory states associated with metabolic diseases, including diabetes, are impacted by diet. Furthermore, diet may modulate the gut microbiome by influencing microbial diversity and richness; dysbiosis of the microbiome is associated with chronic disease. A high fiber diet facilitates a favorable microbiome composition and in turn increases production of intermediate metabolites named short-chain fatty acids (SCFAs) that act on metabolic and immune pathways. In contrast, low fiber diets typically associated with a westernized lifestyle decreases the abundance of microbial derived SCFAs. This decreased abundance is characteristic of metabolic syndromes and activation of chronic inflammatory states, having larger implications in disease pathogenesis of both communicable and non-communicable diseases. Native Hawaiians and Pacific Islanders that once thrived on healthy traditional diets may be more sensitive than non-indigenous peoples to the metabolic perturbation of westernized diets that impinge on the immunoepigenetic-gut microbiome axis. Recent studies conducted in the Maunakea lab at the University of Hawai'i at Mānoa John A. Burns School of Medicine have helped elucidate the connections between diet, microbiome composition, metabolic syndrome, and epigenetic regulation of immune function to better understand disease pathogenesis. Potentially, this research could point to ways to prevent pre-disease conditions through novel biomarker discovery using community-based approaches.

Keywords: COVID-19 severity; SARS-CoV-2; ethnic health disparities; immunoepigenetic-microbiome axis; intestinal microbiome; metabolic syndrome; short-chain fatty acid; type II diabetes risk.

Figure.

Diagram of the Immunoepigenetic-Microbiome Axis. Consumption of a high fiber diet enhances gut microbiome health and metabolic output to decrease systemic inflammation. Abbreviations: HFD, high fiber diet; SCFA, short chain fatty acid; HDAC, histone deacetylase