C0025 - Implications of Butyrate Kinase and Intestinal Microbiota on Diabetes Risk in a Community Enriched With Native Hawaiians

Trevor McCracken, BA, Riley Wells, MS, Braden Kunihiro, BS, Rosa Lee, BS, Noelle Rubas, MS, Rafael Peres-David, PhD, Alika Maunakea, PhD
John A. Burns School of Medicine, Honolulu, HI

Introduction: The incidence of type 2 diabetes mellitus (T2DM) within the Native Hawaiian population among the highest of any major ethnic group within the state of Hawaii. Modern research is beginning to mechanistically understand ancient Hawaiian concepts and practices demonstrating the importance of environment to human health. Environmental factors, such as socioeconomic status, toxicants, diet/nutrition, etc, contribute to individual risk of T2DM, where impacts on the gut microbiome may play key roles in inflammatory and metabolic dysregulation characteristic of diabetes. In this study, we focused on understanding the relationship between the gut microbiome and T2DM risk in the Native Hawaiian population.

Methods: The study enrolled a cohort of Hawaii residents (16 years or older) in a community enriched with Native Hawaiians. Microbial DNA was isolated from self-collected stool samples of all participants and used for 16S amplicon-based sequencing for metagenomic analyses and for quantifying microbial-specific butyrate kinase (BUK) gene expression levels using qPCR approaches. From each participant, anthropometric measures and blood levels of HbA1c, a diagnostic indicator of T2DM, were taken. Blood was collected by venous puncture from which plasma was isolated to measure inflammatory and metabolic biomarkers. Herein, we identified and describe significant differences between diabetic and non-diabetic microbiome composition and diversity.

Results: Consistent with other studies, we observed increased levels of CRP (p< 0.01) and decreased levels of leptin (p=0.04) in the plasma of diabetic compared to non-diabetic participants. Additionally, we observed that BUK levels were negatively correlated with that of HbA1c (R=-0.18, p=0.04), and positively correlated with that of metabolic hormones PYY (R=0.30; p=0.007) and GLP-1 (R=0.19; p=0.04), which were largely attributed to diabetes status. Higher plasma levels of PYY and GLP-1 have previously been associated with reduced T2DM risk.

Discussion: Altogether, our data suggest a role for butyrate-producing gut bacteria in the maintenance of the homeostatic inflammatory and metabolic states that are dysregulated in the progression of T2DM and implicates novel targets for reducing T2DM risk among health disparate populations.


Disclosures:


Trevor McCracken, BA, Riley Wells, MS, Braden Kunihiro, BS, Rosa Lee, BS, Noelle Rubas, MS, Rafael Peres-David, PhD, Alika Maunakea, PhD. C0025 - Implications of Butyrate Kinase and Intestinal Microbiota on Diabetes Risk in a Community Enriched With Native Hawaiians, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.