Faculty Bibliography

The pancreas tumor microbiota may influence tumor microenvironment and influence survival in early-stage pancreatic ductal adenocarcinoma (PDAC); however, current studies are limited and small. We investigated the relationship of tumor microbiota to survival in 201 surgically resected patients with localized PDAC (Stages I-II), from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) cohorts. We characterized the tumor microbiome using RNA-sequencing data. We examined the association of the tumor microbiome with overall survival (OS), via meta-analysis with the Cox PH model. A microbial risk score (MRS) was calculated from the OS-associated microbiota. We further explored whether the OS-associated microbiota is related to host tumor immune infiltration. PDAC tumor microbiome α- and β-diversities were not associated with OS; however, 11 bacterial species, including species of Gammaproteobacteria, confirmed by extensive resampling, were significantly associated with OS (all Q < 0.05). The MRS summarizing these bacteria was related to a threefold change in OS (hazard ratio = 2.96 per standard deviation change in the MRS, 95% confidence interval = 2.26-3.86). This result was consistent across the two cohorts and in stratified analyses by adjuvant therapy (chemotherapy/radiation). Identified microbiota and the MRS also exhibited association with memory B cells and naïve CD4⁺ T cells, which may be related to the immune landscape through BCR and TCR signaling pathways. Our study shows that a unique tumor microbiome structure, potentially affecting the tumor immune microenvironment, is associated with poorer survival in resected early-stage PDAC. These findings suggest that microbial mechanisms may be involved in PDAC survival, potentially informing PDAC prognosis and guiding personalized treatment strategies.IMPORTANCEMuch of the available data on the PDAC tumor microbiome and survival are derived from relatively small and heterogeneous studies, including those involving patients with advanced stages of pancreatic cancer. There is a critical knowledge gap in terms of the tumor microbiome and survival in early-stage patients treated by surgical resection; we expect that advancements in survival may initially be best achieved in these patients who are treated with curative intent.

BACKGROUND:Minoritized populations face many barriers to accessing evidence-based diabetes intervention. OBJECTIVES/OBJECTIVE:To evaluate the feasibility, acceptability, and potential efficacy of a social media-based intervention to improve glycemic control among Chinese Americans with type 2 diabetes. DESIGN/METHODS:A pilot randomized controlled trial (RCT) with 3-month and 6-month follow-ups. PARTICIPANTS/METHODS:Chinese Americans (n = 60, mean age 54.3 years old) with limited education (70.0% with high school or less) and low income (50.0% with annual household income < $25,000), and 88.3% have limited English proficiency. INTERVENTION/METHODS:Culturally and linguistically tailored diabetes videos (two videos/week for 12 weeks) delivered via social media and support calls from community health workers. MAIN MEASURES/METHODS:Primary outcomes include feasibility (video watch rate, biweekly call completion rate, and retention rates), acceptability (patient satisfaction), and HbA1c. Secondary health-related outcomes include body weight, BMI, physical activity, and dietary intake. Video watch rate and biweekly call completion rate were assessed at baseline and 3 months, while others were measured at baseline, 3 months, and 6 months. RESULTS:We observed high feasibility and acceptability of the intervention, with retention rates over 87%, an 89% video watch rate, 80% biweekly phone call completion, and a satisfaction rating of 9 out of 10. The intervention group showed a significantly greater increase in fruit intake compared to the control group (0.15 cups vs. - 0.44 cups, adj_p = 0.023) at 3 months. While no significant differences in other outcomes were observed between the groups, the intervention group showed significant improvements in key outcomes, including reduced HbA1c levels (- 1.08%, adj_p < 0.001), weight loss (- 5.15 lbs, adj_p = 0.004), lower BMI (- 0.83, adj_p = 0.023), and reduced starchy food intake (- 0.33 cups, adj_p = 0.033) at 6 months. CONCLUSIONS:The observed high feasibility and acceptability suggest the intervention's feasibility. However, due to the limited sample size, a larger-scale RCT is warranted to test the efficacy of the intervention. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT03557697; https://clinicaltrials.gov/ct2/show/NCT03557697.

BACKGROUND & AIMS/UNASSIGNED:Metabolic syndrome-associated steatotic liver disease (MASLD) and metabolic syndrome-associated steatohepatitis (MASH) have global prevalence rates exceeding 25% and 3-6%, respectively. The introduction of high-fructose corn syrup to the diet in the 1970s has been linked to metabolic and hepatic disturbances. Despite these associations, the potential for sex-dependent responses resulting from fructose-containing diets on MASLD/MASH has not been addressed. METHODS/UNASSIGNED:standard chow for 16 weeks (n = 40 mice). At sacrifice, plasma and liver were retrieved, the latter for single-nucleus RNA sequencing. Publicly available data sets of human male and female MASH liver were probed. RESULTS/UNASSIGNED:0.0001). Single-nucleus RNA sequencing revealed distinct sex-specific transcriptional profiles in hepatocytes and stellate cells responding to the FPC-NASH diet compared to the standard chow. In female mice, compared to males, pathways associated with lipid and metabolic processes in hepatocytes and cell-cell communication and adhesion in stellate cells were enriched. Metabolic flux analyses demonstrated reduced bile acid metabolism in female mice and human hepatocytes in FPC-NASH and MASH conditions, respectively, compared to their male counterparts. CONCLUSIONS/UNASSIGNED:Molecular profiling of hepatocytes and stellate cells in FPC-NASH diet-fed mice revealed significant sex differences mirrored in human MASH. The identification of intrinsic, within-sex, diet-dependent disparities underscores the critical need to include both male and female individuals in MAFLD/MASH studies and clinical trials. IMPACT AND IMPLICATIONS/UNASSIGNED:male patients with MASH. These results highlight potential mechanistic explanations and therapeutic targets for addressing sex differences and underscore the need to study both sexes in animal models and human MASH.

BACKGROUND:Type 2 diabetes (T2D) contributes to significant morbidity and mortality for Chinese immigrants in the United States, exacerbated by social determinants of health (SDOH) barriers such as language barriers, limited access to healthy foods, and low health literacy. OBJECTIVE:The goal of the Integrating Cultural Aspects into Diabetes Education (INCLUDE) study is to test a social media-based intervention adapting the Diabetes Prevention Program (DPP) for Chinese immigrants alongside a culturally adapted, community-supported agriculture program. Here, we report the protocol for the INCLUDE study. METHODS:INCLUDE is a 3-year randomized controlled trial (n=150). Participants with prediabetes or at risk for T2D are enrolled and randomized into either the control or intervention group (n=75 each). Participants from the intervention group receive 2-3 culturally tailored, in-language DPP videos weekly for 12 weeks, as well as biweekly phone calls from bilingual study staff to review video content, support goal setting, and assess and address SDOH-related barriers such as food insecurity. Intervention participants will also be given produce for 10 weeks as part of the community-supported agriculture program. Weight (primary outcome), self-efficacy, diet, physical activity, and food insecurity (secondary outcomes) are measured at baseline, 3-month, and 6-month intervals. Splined linear mixed models will be used to examine group differences in longitudinal weight and other secondary outcomes. The INCLUDE study was approved by the Institutional Review Board at the NYU Grossman School of Medicine. RESULTS:Recruitment started in May 2023, with the first cohort of 75 participants enrolled and randomized into 2 groups in July 2023. The 3-month and 6-month assessment of the first-year cohort has been completed. We have recruited 75 participants for the second cohort as of July 2024. CONCLUSIONS:The INCLUDE study will serve as an innovative model for culturally adapted, multilevel interventions for underserved communities previously unable to access evidence-based diabetes prevention initiatives. Aligning with several national calls for multilevel interventions, the INCLUDE intervention will provide critical data that will inform how researchers and public health professionals address SDOH barriers faced by underserved populations and prevent diabetes. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT05492916; https://clinicaltrials.gov/study/NCT05492916. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)/UNASSIGNED:DERR1-10.2196/65455.

IMPORTANCE/UNASSIGNED:The oral microbiota may be involved in development of head and neck squamous cell cancer (HNSCC), yet current evidence is largely limited to bacterial 16S amplicon sequencing or small retrospective case-control studies. OBJECTIVE/UNASSIGNED:To test whether oral bacterial and fungal microbiomes are associated with subsequent risk of HNSCC development. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Prospective nested case-control study among participants providing oral samples in 3 epidemiological cohorts, the American Cancer Society Cancer Prevention Study II Nutrition Cohort, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, and the Southern Community Cohort Study. Two hundred thirty-six patients who prospectively developed HNSCC were identified during a mean (SD) of 5.1 (3.6) years of follow-up. Control participants who remained HNSCC free were selected by 2:1 frequency matching on cohort, age, sex, race and ethnicity, and time since oral sample collection. Data analysis was conducted in 2023. EXPOSURES/UNASSIGNED:Characterization of the oral bacterial microbiome using whole-genome shotgun sequencing and the oral fungal microbiome using internal transcribed spacer sequencing. Association of bacterial and fungal taxa with HNSCC was assessed by analysis of compositions of microbiomes with bias correction. Association with red and orange oral pathogen complexes was tested by logistic regression. A microbial risk score for HNSCC risk was calculated from risk-associated microbiota. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was HNSCC incidence. RESULTS/UNASSIGNED:The study included 236 HNSCC case participants with a mean (SD) age of 60.9 (9.5) years and 24.6% women during a mean of 5.1 (3.6) years of follow-up, and 485 matched control participants. Overall microbiome diversity at baseline was not related to subsequent HNSCC risk; however 13 oral bacterial species were found to be differentially associated with development of HNSCC. The species included the newly identified Prevotella salivae, Streptococcus sanguinis, and Leptotrichia species, as well as several species belonging to beta and gamma Proteobacteria. The red/orange periodontal pathogen complex was moderately associated with HNSCC risk (odds ratio, 1.06 per 1 SD; 95% CI, 1.00-1.12). A 1-SD increase in microbial risk score (created based on 22 bacteria) was associated with a 50% increase in HNSCC risk (multivariate odds ratio, 1.50; 95% CI, 1.21-1.85). No fungal taxa associated with HNSCC risk were identified. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This case-control study yielded compelling evidence that oral bacteria are a risk factor for HNSCC development. The identified bacteria and bacterial complexes hold promise, along with other risk factors, to identify high-risk individuals for personalized prevention of HNSCC.

BACKGROUND:Risk of early-stage lung adenocarcinoma (LUAD) recurrence after surgical resection is significant, and post-recurrence median survival is approximately two years. Currently there are no commercially available biomarkers that predict recurrence. Here, we investigated whether microbial and host genomic signatures in the lung can predict recurrence. METHODS:In 91 early-stage (Stage IA/IB) LUAD-patients with extensive follow-up, we used 16s rRNA gene sequencing and host RNA-sequencing to map the microbial and host transcriptomic landscape in tumor and adjacent unaffected lung samples. RESULTS:23 out of 91 subjects had tumor recurrence over 5-year period. In tumor samples, LUAD recurrence was associated with enrichment with Dialister, Prevotella, while in unaffected lung, recurrence was associated with enrichment with Sphyngomonas and Alloiococcus. The strengths of the associations between microbial and host genomic signatures with LUAD recurrence were greater in adjacent unaffected lung samples than in the primary tumor. Among microbial-host features in the unaffected lung samples associated with recurrence, enrichment with Stenotrophomonas geniculata and Chryseobacterium were positively correlated with upregulation of IL-2, IL-3, IL-17, EGFR, HIF-1 signaling pathways among the host transcriptome. In tumor samples, enrichment with Veillonellaceae Dialister, Ruminococcacea, Haemophilus Influenza, and Neisseria were positively correlated with upregulation of IL-1, IL-6, IL17, IFN, and Tryptophan metabolism pathways. CONCLUSIONS:Overall, modeling suggested that a combined microbial/transcriptome approach using unaffected lung samples had the best biomarker performance (AUC=0.83). IMPACT/CONCLUSIONS:This study suggests that LUAD recurrence is associated with distinct pathophysiological mechanisms of microbial-host interactions in the unaffected lung rather than those present in the resected tumor.

Prostate-specific antigen (PSA)-based prostate cancer screening is a preference-sensitive decision for which experts recommend a shared decision making (SDM) approach. This study aimed to examine PSA screening SDM in primary care. Methods included qualitative analysis of audio-recorded patient-provider interactions supplemented by quantitative description. Participants included 5 clinic providers and 13 patients who were: (1) 40-69 years old, (2) Black, (3) male, and (4) attending clinic for routine primary care. Main measures were SDM element themes and "observing patient involvement in decision making" (OPTION) scoring. Some discussions addressed advantages, disadvantages, and/or scientific uncertainty of screening, however, few patients received all SDM elements. Nearly all providers recommended screening, however, only 3 patients were directly asked about screening preferences. Few patients were asked about prostate cancer knowledge (2), urological symptoms (3), or family history (6). Most providers discussed disadvantages (80%) and advantages (80%) of PSA screening. Average OPTION score was 25/100 (range 0-67) per provider. Our study found limited SDM during PSA screening consultations. The counseling that did take place utilized components of SDM but inconsistently and incompletely. We must improve SDM for PSA screening for diverse patient populations to promote health equity. This study highlights the need to improve SDM for PSA screening.

UNLABELLED:With the development of sequencing technology and analytic tools, studying within-species variations enhances the understanding of microbial biological processes. Nevertheless, most existing methods designed for strain-level analysis lack the capability to concurrently assess both strain proportions and genome-wide single nucleotide variants (SNVs) across longitudinal metagenomic samples. In this study, we introduce LongStrain, an integrated pipeline for the analysis of large-scale metagenomic data from individuals with longitudinal or repeated samples. In LongStrain, we first utilize two efficient tools, Kraken2 and Bowtie2, for the taxonomic classification and alignment of sequencing reads, respectively. Subsequently, we propose to jointly model strain proportions and shared haplotypes across samples within individuals. This approach specifically targets tracking a primary strain and a secondary strain for each subject, providing their respective proportions and SNVs as output. With extensive simulation studies of a microbial community and single species, our results demonstrate that LongStrain is superior to two genotyping methods and two deconvolution methods across a majority of scenarios. Furthermore, we illustrate the potential applications of LongStrain in the real data analysis of The Environmental Determinants of Diabetes in the Young study and a gastric intestinal metaplasia microbiome study. In summary, the proposed analytic pipeline demonstrates marked statistical efficiency over the same type of methods and has great potential in understanding the genomic variants and dynamic changes at strain level. LongStrain and its tutorial are freely available online at https://github.com/BoyanZhou/LongStrain. IMPORTANCE/OBJECTIVE:The advancement in DNA-sequencing technology has enabled the high-resolution identification of microorganisms in microbial communities. Since different microbial strains within species may contain extreme phenotypic variability (e.g., nutrition metabolism, antibiotic resistance, and pathogen virulence), investigating within-species variations holds great scientific promise in understanding the underlying mechanism of microbial biological processes. To fully utilize the shared genomic variants across longitudinal metagenomics samples collected in microbiome studies, we develop an integrated analytic pipeline (LongStrain) for longitudinal metagenomics data. It concurrently leverages the information on proportions of mapped reads for individual strains and genome-wide SNVs to enhance the efficiency and accuracy of strain identification. Our method helps to understand strains' dynamic changes and their association with genome-wide variants. Given the fast-growing longitudinal studies of microbial communities, LongStrain which streamlines analyses of large-scale raw sequencing data should be of great value in microbiome research communities.

PURPOSE/OBJECTIVE:We developed a comprehensive sleeve gastrectomy (SG) weight loss study cohort and biorepository to uncover mechanisms, biomarkers and predictive factors of weight loss, weight maintenance and amelioration of obesity-related comorbidities. For this purpose, we collected psychosocial, anthropometric, clinical data and a variety of samples pre-surgery, intraoperatively and 1.5, 3, 12 and 24 months post-surgery. For longer-term assessment, the collection of psychosocial and anthropometric data was extended to 10 years. Here, we present in-depth characterisation of the cohort and detailed overview of study procedures as a foundation for future analyses. PARTICIPANTS/METHODS:We consented 647 participants between June 2017 and March 2020 from two bariatric surgery clinics in New York City-one major urban hospital and one private hospital. Of 355 participants who provided baseline data, 300 underwent SG. Of these, 79% are females with an average age of 38 years, 68% are Hispanic, 20% are non-Hispanic Black and 11% are non-Hispanic White. FINDINGS TO DATE/RESULTS:We collected intraoperative adipose and stomach tissues from 282 patients and biosamples (blood, urine, saliva, stool) from 245 patients at 1.5 months, 238 at 3 month, 218 at 12 months and 180 at 24 months post-surgery. We are currently collecting anthropometric and psychosocial data annually until 10 years post-surgery. Data analysis is currently underway. FUTURE PLANS/UNASSIGNED:Our future research will explore the variability in weight loss outcomes observed in our cohort, particularly among Black and Hispanic patients in comparison to their White counterparts. We will identify social determinants of health, metabolic factors and other variables that may predict weight loss success, weight maintenance and remission of obesity-related comorbidities. Additionally, we plan to leverage our biorepository for collaborative research studies. We will complete long-term follow-up data by December 2031. We plan to apply for funding to expand biosample collection through year 10 to provide insights into the mechanisms of long-term weight maintenance.

BACKGROUND:The Diabetes Telemedicine Mediterranean Diet (DiaTeleMed) Study is a fully remote randomized clinical trial evaluating personalized dietary management in individuals with type 2 diabetes (T2D). The study aims to test the efficacy of a personalized behavioral approach for dietary management of moderately controlled T2D, versus a standardized behavioral intervention that uses one-size-fits-all dietary recommendations, versus a usual care control (UCC). The primary outcome will compare the impact of each intervention on the mean amplitude of glycemic excursions (MAGE). METHODS:Eligible participants are between 21 and 80 years of age diagnosed with moderately controlled T2D (HbA1c: 6.0 to 8.0%) and managed on lifestyle alone or lifestyle plus metformin. Participants must be willing and able to attend virtual counseling sessions and log meals into a dietary tracking smartphone application (DayTwo), and wear a continuous glucose monitor (CGM) for up to 12 days. Participants are randomized with equal allocation (n = 255, n = 85 per arm) to one of three arms: (1) Personalized, (2) Standardized, or (3) UCC. Measurements occur at 0 (baseline), 3, and 6 months. All participants receive isocaloric energy and macronutrient targets to meet Mediterranean diet guidelines, in addition to 14 intervention contacts over 6 months (4 weekly then 10 biweekly) to cover diabetes self-management education. The first 4 UCC intervention contacts are delivered via synchronous videoconferences followed by educational video links. Participants in Standardized receive the same educational content as those in the UCC arm, following the same schedule. However, all intervention contacts are conducted via synchronous videoconferences, paired with Social Cognitive Theory (SCT)-based behavioral counseling, plus dietary self-monitoring of planned meals using a mobile app that provides real-time feedback on calories and macronutrients. Participants in the Personalized arm receive all elements of the Standardized intervention, in addition to real-time feedback on predicted post-prandial glycemic response (PPGR) to meals and snacks logged into the mobile app. DISCUSSION/CONCLUSIONS:The DiaTeleMed Study aims to address an important gap in the current landscape of precision nutrition by determining the contributions of behavioral counseling and personalized nutrition recommendations on glycemic control in individuals with T2D. The fully remote methodology of the study allows for scalability and innovative delivery of personalized dietary recommendations at a population level. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT05046886. Registered on September 16, 2021.