# Longitudinal Study of Early NAFLD Progression and the Gut Microbiome in Asian Americans, Native Hawaiians and Whites > **NIH NIH R01** · UNIVERSITY OF HAWAII AT MANOA · 2024 · $401,212 ## Abstract PROJECT SUMMARY / ABSTRACT This Administrative Supplement application is submitted under PA-20-272 in response to NOT-AG-23-032. In the parent project (R01 MD018265; 2022-2027; “APS2”), we are assessing the early progression of non- alcoholic fatty liver disease (NAFLD) and liver fibrosis over 10 years from mid to late adulthood and evaluating the role of the gut microbiome in mediating the effect of diet on the liver outcome in a subset of the population- based Multiethnic Cohort (MEC) among Hawaii participants from three racial/ethnic groups (Asian, Native Hawaiian, White) with known disparate susceptibility to NAFLD. In this supplement request, we propose to investigate the relationship of the gut microbiome, NAFLD, and Alzheimer's disease and related dementias (ADRD) in the full MEC and the baseline APS1. We showed an up to 2-fold difference in age-adjusted risk of AD/ADRD across the five racial/ethnic groups in MEC based on Medicare claims data, with the highest risks and the highest frequency of APOE ε4 risk allele carriers found among African Americans as previously reported and also Native Hawaiians (Alzheimer's & Dementia 2022). While we replicated the association of known risk factors with ADRD in the MEC (Alzheimer's & Dementia 2023), only one third of the 16,410 cases were explained by known risk factors including APOE, and this population attributable fraction varied substantially by race/ethnicity. These findings underscore the need to identify additional risk factors for ADRD, especially contributors to the striking racial/ethnic disparities. Emerging evidence suggests that the highly prevalent NAFLD, detected in over 30% of older adults, is a risk factor for ADRD/dementia and that pro-inflammatory gut microbiota may promote neuroinflammatory etiology of ADRD, corroborating the putative liver-brain axis. Thus, we propose to (Aim 1a) evaluate the association of NAFLD with subsequent ADRD risk in a longitudinal analysis of the MEC cohort (21,770 ADRD cases, over 20y of follow-up) and also to (Aim 1b) assess the relationship between an exclusive biomarker of microbial inflammation (plasma LBP) and the NIA-designated sole clinical biomarker for neuro- inflammation (plasma GFAP) in a nested case-control study of 500 pairs of ADRD cases and controls, composed evenly of women and men and five racial/ethnic groups. Separately, in the subset of the 300 MEC participants without history of ADRD who are being followed for the parent APS2, we will analyze the baseline APS1 data and archived blood samples to (Aim 2) explore the relationship of 16S rRNA gene sequence-based gut microbial features (alpha and beta diversity, taxa composition, imputed functions), MRI measurement of liver fat, and the plasma neuroinflammation marker GFAP. The proposed study is within the scope and timeline of the parent project supported by NIMHD to better understand the impact of the gut microbiome and NAFLD and to better represent and promote racial/ethnic minority ... ## Key facts - **NIH application ID:** 10940527 - **Project number:** 3R01MD018265-03S1 - **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA - **Principal Investigator:** Meredith Hullar - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $401,212 - **Award type:** 3 - **Project period:** 2022-09-26 → 2027-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10940527 ## Citation > US National Institutes of Health, RePORTER application 10940527, Longitudinal Study of Early NAFLD Progression and the Gut Microbiome in Asian Americans, Native Hawaiians and Whites (3R01MD018265-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10940527. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*