Gut microbial indicators of metabolic health underlie age-related differences in obesity and diabetes risk among Native Hawaiians and Pacific Islanders

Abstract

Native Hawaiians and Pacific Islanders (NHPIs) suffer from higher prevalence of and mortality to type 2 diabetes mellitus (T2DM) than any other major race/ethnic group in Hawaii. Health inequities in this indigenous population was further exacerbated by the SARS-CoV-2 pandemic. T2DM progression and medical complications exacerbated by COVID-19 are partially regulated by the gut microbiome. However, there is limited understanding of the role of gut bacteria in the context of inflammation-related diseases of health disparities including T2DM and obesity. To address these gaps, we used a community-based research approach from a cohort enriched with NHPI residents on the island of Oahu, Hawaii (N=138). Gut microbiome profiling was achieved via 16s rDNA metagenomic sequencing analysis from stool DNA. Gut bacterial capacity for butyrate-kinase (BUK)-mediated fiber metabolism was assessed using quantitative PCR to measure the abundance of BUK DNA and RNA relative to total bacterial load per stool sample. In our cohort, age positively correlated with hemoglobin A1c (%; R=0.39; P<0.001) and body mass index (BMI; R=0.28; P<0.001). The relative abundance of major gut bacterial phyla significantly varied across age groups, including Bacteroidetes (P<0.001), Actinobacteria (P=0.007), and Proteobacteria (P=0.008). A1c was negatively correlated with the relative levels of BUK DNA copy number (R=-0.17; P=0.071) and gene expression (R=-0.33; P=0.003). Interestingly, we identified specific genera of gut bacteria potentially mediating the effects of diet on metabolic health in this cohort. Additionally, α-diversity among gut bacterial genera significantly varied across T2DM and BMI categories. Together, these results provide insight into age-related differences in gut bacteria that may influence T2DM and obesity in NHPIs. Furthermore, we observed overlapping patterns between gut bacteria and T2DM risk factors, indicating more nuanced, interdependent interactions among these factors as partial determinants of health outcomes. This study adds to the paucity of NHPI-specific data to further elucidate the biological characteristics associated with pre-existing health inequities in this racial/ethnic group that is significantly underrepresented in biomedical research.

SARS‐CoV‐2 infection alters the gut microbiome in diabetes patients: A cross‐sectional study from Bangladesh

“…For example, Shigella, Bacteroides, Enterococcus , and Megasphaera were the core pathogens and/or opportunists to be associated with both T2DM and COVID‐19. Our observation of dynamic shifts in gut microbiome between T2DM (i.e., D and CD) and non‐T2DM (i.e., CWD) is supported by many of the previous literature reporting that the SARS‐CoV‐2 diabetic group exhibited a significant increase in pathogens and co‐infection‐causing bacteria with a simultaneous depletion of commensal flora 36,42 . The search for a core microbiome in host‐associated microbial communities is a useful first step in trying to understand the interactions that may be occurring between a host and its microbiome 47 .…”

“…And, age-related differences in gut bacteria may influence T2DM and obesity in humans. 42 We found that some orders of bacteria, for example, Enterobacteriales, Clostridiales, Bifidobacteriales, Lactobacillales, and Micrococcales, had relatively higher abundance levels in CD compared to D and HC subjects. These changes were even more intriguing at the genus-level composition and relative abundances of the gut microbiomes.…”

“…Our observation of dynamic shifts in gut microbiome between T2DM (i.e., D and CD) and non-T2DM (i.e., CWD) is supported by many of the previous literature reporting that the SARS-CoV-2 diabetic group exhibited a significant increase in pathogens and coinfection-causing bacteria with a simultaneous depletion of commensal flora. 36,42 The search for a core microbiome in host-associated microbial communities is a useful first step in trying to understand the interactions that may be occurring between a host and its microbiome. 47 In accordance with the prevailing core microbiome concept, a stable association between T2DM and COVID-19-specific microorganisms suggests these taxa may be functionally necessary for the integrity of the gut microbiome of both diseased and HC humans.…”

“…Existing literature suggest that Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria largely (roughly 97%) compose the gut bacterial population in T2DM. And, age‐related differences in gut bacteria may influence T2DM and obesity in humans 42 …”

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

“…16s metagenomic sequencing DNA (40 ng) isolated from each stool sample was subjected to polymerase chain reaction (PCR) amplification targeting 16s rDNA hypervariable regions V2-4 and V6-9 as we previously performed (Wells et al, 2022). Briefly, amplicon products were pooled (20 μL per primer set), purified (Agencourt Ampure XP Kit; Beckman Coulter, Brea, CA, United States), and quantified using the Qubit dsDNA BR Assay (ThermoFisher Scientific, Warrington, England).…”