Faculty Bibliography

Enteric hyperoxaluria (EH) results from increased oxalate bioavailability in the gastrointestinal (GI) tract, often affecting patients with inflammatory bowel disease (IBD). We investigated the pathophysiology of EH in an ileitis mouse model, hypothesizing that fat malabsorption, increased gut permeability, and microbial shifts collectively contribute to the hyperoxaluric phenotype in the setting of GI tract inflammation. SAMP1/YitFc (SAMP1) mice and their parental AKR controls were fed one of three diets varying in fat content (10%, 45%, or 60% kcal), each supplemented with 1% oxalate, for 6 weeks. Plasma (P), urine (U), oxalate (Ox), and creatinine (Cr) levels were measured, while stool lipid species were analyzed using mass spectrometry. Intestinal permeability was assessed using sucralose and ¹³C₂ oxalate gastric gavage in SAMP1 and AKR mice. Histology, qPCR, and Western blotting were performed on kidney, liver, and GI tissues. Microbial DNA was analyzed at the community, genus, and functional levels. Changes in bacterial metabolic pathways were investigated in the mice fed the highest fat content. The oxalobiome of SAMP1 and AKR mice was characterized using our bioinformatics pipeline. On high-fat diets, SAMP1 mice had higher UOx, POx, and PCr levels than AKR mice. Increased levels of diacylglycerols and free fatty acids in SAMP1 stool samples suggested fat malabsorption. A decrease in ZO1 and occludin intestinal expression, coupled with significantly increased urinary sucralose and oxalate levels, indicated increased intestinal permeability. Microbiome analysis revealed the enrichment of Lactobacilli and Bacteroides in SAMP1 mice, with bacterial pathways favoring lipid synthesis and glyoxylate metabolism. Ileal SLC26A6 protein expression was significantly reduced in SAMP1 mice. SAMP1 mice also developed progressive kidney injury with interstitial inflammation. These findings highlight fat malabsorption as a central pathophysiologic disturbance in EH that reduces luminal calcium availability for oxalate binding, is associated with enhanced intestinal permeability, and accompanies microbiome and enzymatic pathway alterations.

BACKGROUND/UNASSIGNED:The gut microbiome is implicated in obesity and type 2 diabetes (T2D), but how diet, body composition, glycemic status, and self-efficacy factors relate to the microbiome in high-risk individuals is not well characterized. The purpose of this post-hoc analysis is to examine the relationship between the gut microbiome and obesity-related metabolic factors, including body composition, resting energy expenditure (REE), and glycemic variability (GV). METHODS/UNASSIGNED: = 95) included the collection of fecal microbiome profile, demographics, socioeconomic status, physical and metabolic characteristics [fat mass, fat free mass (FFM), continuous glucose monitoring-derived GV, REE], self-efficacy and dietary intake. Gut bacterial alpha diversity, beta diversity, and genus level abundances were associated with these host and lifestyle variables using multivariate regression, permutational multivariate analysis of variance, and correlation analyses. RESULTS/UNASSIGNED:ratio was positively associated with total energy, sugar, and carbohydrate intake (g/day) and negatively associated with monounsaturated fat intake (g/day). Glycemic measures and self-efficacy were not associated with any genera. CONCLUSION/UNASSIGNED:In adults with prediabetes and obesity, the gut microbiome at baseline was most strongly associated with diet, with additional associations observed for body composition and selected host characteristics. These findings underscore diet as a key correlate of gut microbiome structure in a high-risk metabolic population and support further development of microbiome-informed precision nutrition strategies for obesity prevention and management.

BACKGROUND:Over 90% of Asian American (AsA) adults are first- or second-generation immigrants, undergoing substantial environmental and sociocultural transitions; yet most environmental epidemiology cohorts have included few AsA participants. METHODS:The Food and Microbiome Longitudinal Investigation (FAMiLI) is an environmental health cohort enriched with AsA adults (predominantly Korean and Chinese American) and designed to capture environmental exposures, dietary acculturation, and sociocultural factors across immigration generations. Its biobank-including buccal and stool specimens-supports research on the oral and gut microbiomes, human genomics, and other multi-omics. RESULTS:Since its launch in 2018, FAMiLI has completed baseline recruitment and biospecimen collection for 13,183 adults aged 40-75 years. The cohort is now expanding to include an additional 3,000 Asian American adults, bringing the total to approximately 16,000 participants, with an expected distribution of ~50% Asian American and ~50% from other racial/ethnic groups. This expansion provides an opportunity to examine AsA environmental health experiences within the broader U.S. CONCLUSIONS:FAMiLI is a unique national resource to address priority questions in environmental health, including microbiome and exposome science, individual susceptibility, and large-scale data analytics. IMPACT/CONCLUSIONS:The cohort supports investigation of critical windows of environmental change across the immigration experience, racial and ethnic disparities, and drivers of emerging health outcomes, including cancer, cardiovascular disease, diabetes and other outcomes. This cohort offers essential data to inform prevention strategies and shape public health policy to improve health outcomes in AsA communities.

BACKGROUND/UNASSIGNED:Prediabetes is common in the United States, and adverse social determinants of health (SDOH) are known to undermine diabetes prevention efforts. Chinese Americans experience a disproportionately high prevalence of prediabetes, yet the SDOH profiles of this population remain understudied. OBJECTIVE/UNASSIGNED:This study assessed SDOH among Chinese Americans at risk for diabetes and examined the associations between sociodemographic characteristics and SDOH barriers. METHODS/UNASSIGNED:We conducted a cross-sectional analysis of baseline survey data from the Integrating Cultural Aspects into Diabetes Education (INCLUDE) study, a randomized controlled trial of a culturally and linguistically tailored mobile diabetes prevention intervention for Chinese Americans. Participants at risk for diabetes were enrolled between April 2023 and June 2024 in New York City (N=150). Measures included in the analyses were a 14-item SDOH scale (range 0-14, with higher scores indicating more barriers) and sociodemographic characteristics. Due to the small frequencies of high SDOH scores, we collapsed the outcome into 5 categories (0, 1, 2, 3, and 4-14) to improve model stability. We first used univariable logistic regression models to examine associations between each sociodemographic factor (age, sex, years of US residence, English proficiency, education, marital status, employment status, and annual household income) and the collapsed SDOH category, followed by a multivariable ordinal regression model including all sociodemographic variables. RESULTS/UNASSIGNED:A total of 150 participants had a mean age of 49.9 (SD 12.6) years. Most were female (n=124, 82.7%), born outside the United States (n=149, 99.3%), and reported speaking English less than very well (n=132, 88.0%). Among respondents to the SDOH items (n=149), the mean SDOH score was 2.4 (SD 2.3), and 81.9% (n=122) reported at least 1 SDOH barrier. The three most frequently reported barriers were (1) the need to improve English proficiency, reading skills, or educational attainment (n=77, 51.7%); (2) experiences of racial discrimination (n=49, 32.9%); and (3) adverse housing conditions (n=38, 25.5%). After collapsing the original SDOH score, 27 (18.2%) participants had a score of 0, 39 (26.2%) had a score of 1, 23 (15.4%) had a score of 2, 27 (18.2%) had a score of 3, and 33 (22.1%) had scores of 4 to 14. In the multivariable analysis, female sex (vs male) was associated with higher SDOH score categories (odds ratio 3.83, 95% CI 1.65-9.16; P=.002). CONCLUSIONS/UNASSIGNED:SDOH-related barriers were prevalent among Chinese Americans at risk for diabetes. Diabetes prevention efforts should incorporate routine SDOH screening and structured resource navigation or referral pathways, with particular attention to subgroups at higher risk, such as female individuals.

Patients with resected, high-risk melanoma receive adjuvant immune checkpoint blockade (ICB), yet clinical benefit remains unpredictable, with 25%-40% of patients experiencing recurrence. To evaluate whether pre-treatment gut microbiome (GMB) features predict recurrence, we analyzed stool samples from 674 patients enrolled in a phase 3 clinical trial, CheckMate 915, which investigated the combination of nivolumab plus ipilimumab versus nivolumab as a single agent across five geographic regions. Region-specific and cross-region meta-analyses identified pre-treatment taxa associated with recurrence, including Eubacterium, Ruminococcus, Firmicutes, and Clostridium. Recurrence prediction was strongest when the validation cohort exhibited GMB profiles similar to those in the discovery cohort. Among closely matched individuals (Jensen-Shannon divergence [JSD] ≤ 0.11), the area under the curve (AUC) for recurrence prediction ranged from 0.78 to 0.94 across regions. GMB composition remained largely stable following treatment. These findings suggest that gut bacterial markers can predict recurrence after adjuvant ICB treatment in melanoma, supporting their potential as clinically actionable biomarkers to guide personalized therapy.

BACKGROUND:Chinese immigrants face numerous social determinants of health (SDOH) challenges that limit access to evidence-based diabetes self-management education and support programs (DSMES). To address these challenges, our team developed the LINK-IT intervention. This manuscript presents the study protocol for the LINK-IT trial. METHODS:The LINK-IT trial is a 12-month, 3-arm randomized controlled trial aiming to enroll 405 Chinese immigrants with T2D (HbA1c≥7%) from multiple community and clinical settings in New York City. A total of 405 participants will be randomly allocated to one of three groups (n = 135 per group): (1) video-based DSMES plus community health worker (CHW) support (VIDEO+CHW), (2) video-based DSMES only (VIDEO), or (3) wait-list control (CONTROL). The VIDEO+CHW group will receive 24 culturally and linguistically tailored DSMES videos (one per week for 24 weeks) delivered via text message links, along with biweekly (every other week) phone calls from trained CHWs to review video content, support goal setting, and address SDOH barriers. The VIDEO group will receive the same video intervention without CHW support. The CONTROL group will receive usual care and will be offered access to the videos upon study completion. The primary outcome is the change in HbA1c at 6 months. Secondary outcomes include changes in HbA1c at 12 months, self-efficacy for diabetes, dietary intake, physical activity, medication adherence and emotional support at 6 and 12 months. Data will be analyzed using an intention-to-treat approach with linear mixed-effects models. ETHICS AND DISSEMINATION/BACKGROUND:This study protocol has been approved by the Institutional Review Board of the NYU Grossman School of Medicine (S23-01274). All study procedures will adhere to the ethical principles outlined in the Declaration of Helsinki. Written or verbal informed consent will be obtained from all participants. Study results will be disseminated through peer-reviewed publications, presentations at scientific conferences, and community events. TRIAL REGISTRATION/BACKGROUND:The LINK-IT trial was registered on March 20, 2024, on ClinicalTrials.gov under the identifier NCT06319716; https://clinicaltrials.gov/study/NCT06319716.

MOTIVATION/BACKGROUND:Large-scale prospective cohort studies collect longitudinal biospecimens alongside time-to-event outcomes to investigate biomarker dynamics in relation to disease risk. The nested case-control (NCC) design provides a cost-effective alternative to full cohort biomarker studies while preserving statistical efficiency. Despite advances in joint modeling for longitudinal and time-to-event outcomes, few approaches address the unique challenges posed by NCC sampling, non-normally distributed biomarkers, and competing survival outcomes. RESULTS:Motivated by the TEDDY study, we propose "JM-NCC", a joint modeling framework designed for NCC studies with competing events. It integrates a generalized linear mixed-effects model for potentially non-normally distributed biomarkers with a cause-specific hazard model for competing risks. Two estimation methods are developed. fJM-NCC leverages NCC sub-cohort longitudinal biomarker data and full cohort survival and clinical metadata, while wJM-NCC uses only NCC sub-cohort data. Both simulation studies and an application to TEDDY microbiome dataset demonstrate the robustness and efficiency of the proposed methods. AVAILABILITY/BACKGROUND:Software is available at https://github.com/Zhaoyn-oss/JMNCC and archived on Zenodo at https://zenodo.org/records/18199759 (DOI: 10.5281/zenodo.18199759). SUPPLEMENTARY INFORMATION/BACKGROUND:Supplementary data are available at Bioinformatics online.

BACKGROUND/UNASSIGNED:The oral microbiome is vital for health, yet population-based evidence on how self-reported flossing relates to microbial communities remains limited. This study examined the association between self-reported dental flossing frequency and oral microbiome diversity in a nationally representative sample of U.S. adults. METHODS/UNASSIGNED:This cross-sectional analysis included 4,772 adults aged 30-69 from NHANES 2009-2012. Flossing frequency was categorized as non-users (0 days/week), some flossing (1-6 days/week), and daily users (7 days/week). Oral microbiome composition was profiled using 16S rRNA sequencing. α-diversity was calculated using Observed amplicon sequence variants (ASVs), Shannon, Inverse Simpson, and Faith's Phylogenetic Diversity (PD); β-diversity using Bray-Curtis and UniFrac distances. Survey-weighted linear regression and PERMANOVA were used with covariate adjustment. RESULTS/UNASSIGNED: CONCLUSIONS/UNASSIGNED:Frequent flossing was associated with reduced microbial richness and phylogenetic diversity, potentially indicating a favorable shift toward a healthier microbial community.

BACKGROUND:Dietary self-monitoring is central to effective personalized nutrition, providing critical data to inform tailored feedback and support behavior change. OBJECTIVE:To examine the impact of dietary self-monitoring adherence and the indirect effect of personalized scores to predict postprandial glycemic response (PPGR) on weight loss. METHODS:Post-hoc analysis of the Personal Diet Study that investigated the impact of a machine algorithm-based diet that integrates clinical and microbiome features (Personalized) compared to a standard, low-fat diet (Standardized) on weight loss. All participants received behavioral counseling and were encouraged to self-monitor dietary intake via a smartphone app. Personalized received algorithm-based scores (1 to 5) on predicted PPGR to foods logged (PPGR score; 1-2 indicating optimal; 3-5 suboptimal). Dietary self-monitoring adherence was the percentage of days logging ≥50% of target calories, classified as high or low. PPGR score quality was calculated by the proportion of optimal predicted PPGR scores per day; defined as "high-PPGR quality" days when this exceeded the group average. Mediation analysis assessed whether PPGR quality mediated the relationship between dietary self-monitoring adherence and weight loss. RESULTS:Participants with high self-monitoring adherence lost an average of 4.2% of their baseline weight, compared to 1.9% among those with low adherence (p=0.016). High self-monitoring adherence was associated with a greater likelihood of achieving ≥5% weight loss (aOR=3.67, 95% CI: 1.63-8.50). Within Personalized, high PPGR quality mediated 53.4% of the total effect of self-monitoring adherence on weight loss (p<0.001). CONCLUSION/CONCLUSIONS:Consistent self-monitoring coupled with personalized feedback may significantly enhance weight loss in a precision nutrition approach. CLINICAL TRIAL REGISTRATION/BACKGROUND:NCT03336411.

BACKGROUND:levels. However, it remains unclear whether the CARE program also improves diabetes self-efficacy and psychosocial outcomes in the same study sample. OBJECTIVE:This is a secondary analysis to examine the potential efficacy of the CARE program on secondary outcomes, including diabetes self-efficacy, self-care activities, beliefs in diabetes self-care activities, and diabetes distress among Chinese Americans with T2D. METHODS:level of 7% or higher. Participants were recruited from various health care settings in New York City, including community health centers, private primary care providers, and NYU Langone Health and its affiliates, and were randomly assigned to either the CARE intervention group (n=30) or a waitlist control group (n=30). The intervention consisted of 2 culturally and linguistically tailored educational videos per week for 12 weeks, covering diabetes self-care topics such as healthy eating, physical activity, and medication adherence. These videos were delivered via the WeChat app. In addition, community health workers provided support calls to assist them in setting goals, problem-solving, and addressing social determinants of health barriers every 2 weeks. Secondary outcomes included patient self-reported diabetes self-efficacy, self-care activities, beliefs in diabetes self-care activities, and diabetes distress. Outcomes were assessed at baseline, 3 months, and 6 months. RESULTS:Participants had a mean age of 54.3 (SD 11.5) years and 62% (37/60) were male, 78% (47/60) were married, 58% (35/60) were employed, 70% (42/60) had a high school education or lower, and 88% (53/60) reported limited English proficiency. Intervention participants demonstrated statistically significant improvements in self-efficacy at 3 months (estimated difference in change: 8.47; 95% CI 2.44-14.5; adjusted P=.02), diabetes distress at 6 months (estimated difference in change: -0.43; 95% CI -0.71 to -0.15; adjusted P=.009), and adherence to a healthy diet at both 3 months (estimated difference in change: 1.61; 95% CI 0.46-2.75; adjusted P=.02) and 6 months (estimated difference in change: 1.64; 95% CI 0.48-2.81; adjusted P=.02). CONCLUSIONS:The culturally and linguistically tailored intervention showed promise in improving self-efficacy and diabetes self-care activities among Chinese Americans with T2D, warranting validation through a large-scale randomized controlled trial. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT03557697; https://clinicaltrials.gov/study/NCT03557697.