Women remain underrepresented in National Institutes of Health (NIH) study sections, panels of scientists who review grant applications to inform national research priorities and funding allocations. This longitudinal, retrospective study examined the representation of women on study sections before and during the COVID-19 pandemic. Overall, 16,902 reviewers served on 1,045 study sections across 2019, 2020, and 2021, of which 40.1% (n = 6,786) were women. The likelihood of reviewers being women significantly increased from 2019 to 2021, except among chairpersons. Understanding the representation of scientists influencing NIH grant decisions is important to ensuring scientific discovery that meets the nation’s pluralistic needs.

Objectives/Goals: As life expectancy increases in people with HIV, neurocognitive impairment is becoming more common, and women with HIV (WWH) are disproportionately impacted. This work investigated mitochondrial function and oxidative stress in WWH in order to understand the relationship between mitochondrial function and cognition in future studies. Methods/Study Population: Peripheral blood mononuclear cells were isolated from virally suppressed WWH (n = 64) and underwent the Seahorse Cell Mito Stress test to assess different realms of mitochondrial function. Cells were then lysed for direct DNA extraction, and quantitative PCR was performed to understand mitochondrial DNA expression (mtDNA) levels as a measure of oxidative stress. A series of simple linear regressions was then conducted to understand the relationships between mitochondrial function and mtDNA content. Future work will expand this analysis to investigate associations between demographic dynamics, such as trauma history, and mitochondrial function, as well as to understand the relationships between mitochondrial function and cognitive outcomes in WWH. Results/Anticipated Results: In our cross-sectional analysis of mitochondrial dynamics in WWH, we found a significant association between maximum mitochondrial respiration ability and mtDNA content, with greater mtDNA expression associated with increased levels of maximum respiration following stimulation. There was no association between basal respiration and levels of oxidative stress. There was also a significant variation in mitochondrial function in our participants, indicating that future analyses to investigate the source of that variation are warranted. The work presented here sheds light on mitochondrial dynamics in WWH and will be the basis for future studies that will investigate how demographic dynamics may be associated with mitochondrial function, as well as how mitochondrial dynamics may predict cognitive outcomes. Discussion/Significance of Impact: There is significant variation in mitochondrial function in WWH. More analysis is needed to understand what may be associated with these variations, including an investigation of both clinical factors as well as cognitive outcomes. This analysis will inform directions for future mechanistic work aimed at mitigating adverse cognitive outcomes in WWH.

OBJECTIVES/SPECIFIC AIMS: Immune cells within the tumor microenvironment (TME) play an important role in the development and progression of non-small cell lung cancer (NSCLC). However, data evaluating the impact of individual immune cell types on NSCLC outcomes is limited and often conflicting. We performed a meta-analysis of existing data and used The Cancer Genome Atlas (TCGA) to evaluate the effect of several immune cells on surgical outcomes of stage I-IIIA NSCLC. METHODS/STUDY POPULATION: PubMed was searched to identify eligible studies evaluating survival of surgically resected stage I-IIIA NSCLC patients according to immune cell infiltration. Meta-analysis was performed using a linear mixed-effects model to determine overall, disease specific and progression free survival. We then used a similar patient subset found in the TCGA to validate the meta-analysis findings. For the TCGA analysis, sample-specific scores for different immune cells were computed via xCell using level three RNAseq data. After stratifying the cohort by histologic subtype, the association between each cell type and survival was assessed via Cox Regression, while adjusting for stage, gender and smoking status. RESULTS/ANTICIPATED RESULTS: From the meta-analysis (37 articles eligible; N = 8,162 patients), high levels of CD20+ B cells (hazard ratio [HR]: 0.36, 95% confidence interval [CI]: 0.15-0.85), natural killer (NK) cells (HR: 0.64, 95% CI: 0.41-1.0), and dendritic cells (0.34, 95% CI: 0.13-0.84) were significantly associated with better overall survival (OS); T regulatory cells (HR: 1.85, 95% CI: 1.35-2.54) were associated with worst OS. High CD8+ T cell infiltrates were associated with improved disease-free survival (DFS; HR: 0.85, 95% CI 0.73-0.99), while CD68+ macrophages (HR> 2.83, 95% CI: 1.28-6.24) were associated with worst DFS. In the TCGA cohort, lung adenocarcinomas rich in CD4 T cells, CD8 T cells, B cells, and NK cells were associated with improved OS in unadjusted analysis. In adjusted analysis, only NK cells were associated with improved OS (HR: 0.82, 95% CI: 0.69-0.98). There was no significant association of any immune cell type for DFS in lung adenocarcinomas and with both OS and DFS in Squamous Cell Lung Cancers (p>0.05 for all comparisons). DISCUSSION/SIGNIFICANCE OF IMPACT: The presence of tumor infiltration by specific immune cell subsets may potentially predict survival outcomes in resected stage I-III NSCLC patients. However, the impact of immune cells may not be similar in all histologic types and after adjusting for important clinical confounders.

Objectives/Goals: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a mean survival of only 11 months even with the most advanced treatment to date. The desmoplastic microenvironment of PDA is thought to play a critical role in therapy resistance. One pathway that might be responsible for resistance to immunotherapy is the CXCR4-CXCL12 axis. Methods/Study Population: In this study, we propose to evaluate the effect of CXCR4-CXCL12 inhibition on dual checkpoint inhibition in KPC mouse model of PDAC and patient-derived explants. PDAC mouse models are made with pancreatic cancer cells driven by loss of TP53 and activation of KRAS. These models are treated with PD1 inhibitor Balstilimab and an FC-modified CTLA4 Botensilimab with or without CXCR4 inhibitor BL8040. In addition, we make explants of patient tumors along with their tumors and autologous peripheral blood mononuclear cells and this model is similarly challenged with BOT/BAL and BL8040. Using immunofluorescence and flow cytometry, we quantify and evaluate the spatial relationships between different cell populations. Most notably, we evaluate the relative abundance of CD8+ T cells in control and treated conditions. Results/Anticipated Results: We expect the inhibition of CXCR4-CXCL12 axis, along with two new potent checkpoint blockers, will lead to infiltration of CD8+ T cells in both the mouse and human PDAC models. We also expect this to translate into more tumor cell killing as demonstrated by Caspase activities and tumor shrinkage. Discussion/Significance of Impact: If our hypothesis is proven in both mouse and human PDAC models, this study will serve as a basis for a phase I/II clinical trial testing this combination of drug.

OBJECTIVES/GOALS: To establish and develop a high-level, dynamic, and self-sustainable Translational Science – research center in Colombia that promotes and articulates collaborative participation among different disciplines at Universidad de La Sabana to generate impactful solutions in health to transfer the knowledge to the local community. METHODS/STUDY POPULATION: With the support of core units of the University, internal funding was given for the establishment of the Research Center. An internal call was performed for recruiting researchers for multiple disciplines interested in joining the UCTS. After the researchers were selected, training of the research community in translational science and funding acquisition was performed towards the objective of interdisciplinary projects with impact in the local community. Project management strategies have been used for the follow-up of the advancements of the implementation of the UCTS. Operational structure and business plan for future self-sustainability are being designed. UCTS is proposed as an articulating party among different actors in clinics, research, and industry, for science and funding management. RESULTS/ANTICIPATED RESULTS: As an starting point, 8 research groups of different disciplines of the University have been integrated with the UCTS, increasing the research capacity in translational science. Internal administrative processes have been articulated within the institution and unified processes for international grants applications have been established in order to optimize the funding acquisition and management. Training programs for the research community, and community engagement activities have been offered as well. Networking relationships have been strengthened among the researchers enhancing international collaborations. Novel research projects are being designed towards real solutions in health for the local community, promoting the transference of knowledge from the benchside to the community. DISCUSSION/SIGNIFICANCE: The implementation of the UCTS led to the integration of disciplines within the University, towards new research projects with common interests for the local community. It has been an enriched experience using the project management approach, fulfilling a huge milestone for the University, aligned with the internal strategic priorities

OBJECTIVES/SPECIFIC AIMS: Aim 1: To evaluate whether psoas muscle size on CT imaging can be used as univariate predictor for increased risk of morbidity and mortality in trauma patients 65 years or older with rib fractures. Primary outcomes will be 30 day mortality. Secondary outcomes will include length of stay, 30 day readmission rate, need for operative/procedural intervention, ICU days, ventilator days, discharge to rehabilitation. Aim 2: An eventual goal of the project will be to use the results of the single variable psoas size study to inform the development of a predictive model for readmission rate in this population based on clinical variables present at admission. METHODS/STUDY POPULATION: This retrospective cohort study will utilize the Maine Trauma Registry to conduct a database review for all persons 65 years of age and older admitted to Maine Medical Center between January 1, 2015 and December 31, 2017 with rib fracture as diagnosed by CT imaging. Psoas caliber will be measured on admission CT. Patient outcomes will be assessed via EMR review. RESULTS/ANTICIPATED RESULTS: Anticipate finding a relationship between decreased psoas caliber and increase in 30 day mortality and post trauma complications. DISCUSSION/SIGNIFICANCE OF IMPACT: If a relationship is demonstrated between decreased psoas caliber and poor outcomes in elderly patients with rib fractures, this early indicator could be used to identify those patients at most risk, for whom targeted interventions may make the greatest difference. Knowing a measure of frailty could also help guide goals of care discussions, because it would allow clinicians to have a more detailed understanding of a patient’s baseline. Those patients identified as frail could be admitted to an ICU level of care and more closely monitored and treated. Alternatively, some frail patients and their families may choose to focus more on comfort and quality of life after achieving a better understanding of a patient’s frailty and risk, changing the direction of care provided. Being able to identify the higher risk patients with an objective measure would allow clinicians to provide more personalized medicine.

OBJECTIVES/GOALS: High turnover rates of clinical trials staff pose obstacles to the quality and efficiency of conducting clinical trials. We have explored alternative staffing models to address these translational barriers and to improve the financial viability and return on investment of a centralized clinical trials office. METHODS/STUDY POPULATION: Implementation of an alternative clinical trials staffing model that leveraged burnout rates in clinical service areas by hiring APPs, RNs, EMTs, OTs and PTs in tandem with traditional CRAs/CRCs. Financial modelling of employing higher salaried clinical professionals was analyzed with regards to greater staff retention, trials efficiency, and operational cost savings. RESULTS/ANTICIPATED RESULTS: Since 2014, 30 of 51 (59%) staff left the clinical trials office with 49% of these leaving prior to 2 years employment. Using average local CRCII compensation values, the costs associated with these transient staff amounted to $2.51 million (i.e., recruitment, replacement, and training). Models of staffing that replace 2 CRAs, 2 CRCIs and 2 CRCIIs with an RN, APP, CRCI and 3 CRAs increases compensation by 24.1%. This increase, however, is offset by greater workload capacity, retention, and more efficient trials operations. In addition, revenue generating PI clinical activity is sustained by employing credentialed APPs for study visits. DISCUSSION/SIGNIFICANCE: Long-term financial savings and greater clinical trial operational efficiency may be accomplished by seeking clinical professionals looking for alternative opportunities with greater work-life balance while leveraging their advanced clinical skills and licensing.

OBJECTIVES/GOALS: In a 2022 NASEM Report, “… successful inclusion of underrepresented populations in research is investing in diverse research teams to enhance congruence and to optimize recruitment and retention success.” Thus, academic research institutions must provide safe, respectful and inclusive work environments to support diverse research teams. METHODS/STUDY POPULATION: Resources, policies and protocols related to disruptive research participants have not been well articulated at our institution. Given this dearth of information, we launched a new initiative across our CTSA, IRB, Office of General Counsel and Department of Population Health. The multipronged approach includes: 1) Conduct a scoping review of published and gray literature to identify best practices, trainings and resources to mitigate discrimination, harassment of research team members; 2) Co-develop new institutional policies and procedures to ensure safety and respect for both research staff and participants; 3) Develop an online training on research team field and workplace safety; and 4) Widely disseminate policies and resources to address the overall gap in academic research. RESULTS/ANTICIPATED RESULTS: Our ongoing scoping review has shown that here is an overall lack of information on bias, discrimination and harassment perpetrated by research participants towards research teams. Based on our activities, new Human Research Protection policies were launched. These include defining what disruptive participant behavior in research is, the introduction of a Statement on the Conduct of Participants in Research Studies, and steps study teams may implement to manage disruptive behavior initiated by a research participate. Next steps include the development of training resources for study teams on the new policies and to introduce de-escalation and situational awareness strategies and trainings. DISCUSSION/SIGNIFICANCE: As research teams become increasingly diverse, there is a need to better support them and ensure that the research field and work settings are safe, inclusive environments with articulated policies that mitigate/prevent discrimination, bias and harassment perpetrated by study participants.

OBJECTIVES/SPECIFIC AIMS: Projected to soon become the most prevalent cause of End-Stage Liver Disease, the frequency of Non-Alcoholic Fatty Liver Disease (NAFLD) has been rising in the US community. However, studies on NAFLD among inpatients are lacking. Aims: To report the 1) prevalence and trends, 2) outcomes of NAFLD associated hospitalizations in the US. METHODS/STUDY POPULATION: NAFLD cases were identified in the National Inpatient Sample (2007-2014) with ICD-9-CM codes, and the prevalence and trends over the 8-year period were calculated among different demographic groups. After excluding secondary causes of hepatic fat accumulation from the NAFLD cohorts (n = 210,660), the impact of sex, race, and region on outcomes (mortality, discharge disposition, length of stay [LOS] and cost) of NAFLD was computed with generalized estimating equations (SAS 9.4). RESULTS/ANTICIPATED RESULTS: Admissions with NAFLD tripled from 2007-2014 at an average rate of 79/100,000 hospitalizations/year (p-value < 0.0001), with a larger rate of increase among males vs. females (83/100,000 vs. 75/100,000), Hispanics vs. Whites vs. Blacks (107/100,000 vs. 80/100,000 vs. 48/100,000), and governmental-/un-insured patients vs. privately-insured (94/100,000 vs. 74/100,000). Males had higher mortality, LOS and cost than females. Blacks had longer LOS and poorer discharge destination than Whites; while Hispanics and Asians incurred higher cost than Whites. Uninsured patients had higher mortality, longer LOS and poorer discharge disposition than the privately-insured. DISCUSSION/SIGNIFICANCE OF IMPACT: Hospitalizations with NAFLD is rapidly increasing in the US, with a disproportionately higher burden among certain demographic groups. Measures are required to arrest this ominous trend and to eliminate the disparities in outcome among patients hospitalized with NAFLD.

OBJECTIVES/SPECIFIC AIMS: The objective of this study was to reconstruct patient-specific distal airway patterns at the tissue- and single-cell resolution and develop personalized distal airway models based on utilization of patient-derived DABCs and autologous region-specific stromal cells. METHODS/STUDY POPULATION: Patient-specific distal airway units, containing parental small bronchiole (<2 mm in diameter, >12th generation) and daughter airway branches, including pre-terminal/terminal bronchioles, leading to alveoli (3-7 units/lung), were dissected. Epithelial and stromal cells were isolated from these units and processed for ddSeq single-cell RNA-sequencing (n=6 samples). Autologous DABCs and stromal cells were isolated, propagated, biobanked, and used for establishment of patient-specific distal airway models (3D-organoids and air-liquid interface-based airway wall model; n=10 samples). Region-specific tissue patterns were evaluated using immunofluorescence and laser-capture microdissection (LCM; n=6 samples). RESULTS/ANTICIPATED RESULTS: Single-cell-based human distal airway transcriptome map (constructed based on the analysis of >6,500 distal airway cells obtained from 6 subjects) identified physiological and COPD-relevant distal airway differentiation patterns, including distal airway-specific secretory phenotype (DASP) characterized with high expression of secretoglobins 3A2 and 3A1, surfactant proteins SFTPB and SFTPA2, and mucin 1, unique signatures of DABCs, and stromal (fibroblasts, smooth muscle, endothelial cell subpopulations) and immune (macrophage, T cells, B cell, mast cells). Immunofluorescence analysis and LCM confirmed distribution of cell type-specific markers with differential expression patterns of DABC and DASP signatures. Patient-derived DABC-stromal co-culture models reproduced 3 regenerative patterns: 1) physiological (high DABC-clonogenic potency, establishment of polarized differentiated organoids and DASP-expressing epithelia); 2) hypo-regenerative (failure of DABCs to form clones, spheres and mechanically stable differentiated epithelial barrier); and 3) hyperplastic (generation of DABC hyperplasia accompanied in some COPD samples by mucous-cell hyperplasia mimicking in vivo remodeling patterns). DISCUSSION/SIGNIFICANCE OF IMPACT: Patient-specific maps and models of distal airway regeneration patterns have been established in this study, which can be used to identify candidate pathways that mediate disease-relevant airway remodeling and potentially utilized as pre-clinical platforms for developing personalized therapeutic approaches to suppress the progression of distal airway remodeling in chronic lung diseases, including COPD.

OBJECTIVES/GOALS: Academic research is often viewed as a necessary core mission but a financial loss requiring central or clinical funds support. We present cases as evidence of sustaining academic unit research endeavors through strategic planning and reinvestment of sponsored clinical trials residuals. METHODS/STUDY POPULATION: Successful endeavors are presented that demonstrate strategic reinvestment of clinical trials residuals to develop robust academic self-sustaining research programs. A multi-year strategic plan was developed leveraging residuals from sponsored clinical trials to build an academic research infrastructure supporting extramural grant applications, pilot studies, pre- and post-award management, equipment investment, and faculty incentives. RESULTS/ANTICIPATED RESULTS: Example 1, pooling four existing department clinical trials generated yearly profits that expanded clinical trials capacity and used residuals to support a grant coordinator. Over 7 years, trial volume increased to near 50, revenue increased to $2.5 million annually, staffing increased to 20 FTEs, and extramural grant applications increased from 16 to 50. Example 2 started with a department with no infrastructure. Central support was leveraged for 6-months to support a coordinator to initiate a clinical trials program. The initial investment was offset by trials earnings by year 2, breaking even financially, while establishing a nascent yet robust infrastructure to build autonomously without additional central funding requests. DISCUSSION/SIGNIFICANCE: Utilizing sponsored clinical trials as a strategic investment fund, academic units can realize fiscally responsible expansion of research activities and national recognition through acquisition of extramural funding and investigator-initiated investigations.

OBJECTIVES/GOALS: A strategic initiative of Mayo Clinic is to decrease clinical trial activation timelines by 25% from 2022 levels. The team’s goal is to streamline activation via parallel processing, improved collaboration with business units, project manager facilitation, and early study coordinator involvement. METHODS/STUDY POPULATION: The workgroup targeted industry trials, focusing on key financial, regulatory, and operational elements. Current state process workflows and pain points were prepared and opportunities for concurrent activities or automation identified. The scope of the project manager role from the Office of Clinical Trials was extended to guide each activation team, who have varying levels of experience, to maintain timelines until the trial is opened. Coordinators responsible for study conduct engaged in key operational discussions earlier to ensure the trial will be run successfully. A Pilot program is utilizing the identified concurrent activities, project manager support, and earlier coordinator involvement to gauge effectiveness of the proposed solutions. RESULTS/ANTICIPATED RESULTS: The goal is for 120 industry clinical trials to join the Pilot program and to open enrollment in less than 30 weeks from being document ready. As of Q3 2023, 109 clinical trials across multiple Mayo sites have enrolled in the pilot. Thirty-five (85 percent) of 41 Pilot trials have opened to enrollment and have met the goal, with a median timeline of 24 weeks. Twenty-one (21) trials opened to enrollment in Q3 2023 with a median timeline of 23 weeks, representing 24% of all industry clinical trials opened that quarter. Opening trials and monitoring is ongoing and PI and study team feedback is positive. DISCUSSION/SIGNIFICANCE: Using a team-based approach, we identified key areas for optimization and parallel processing. The solution reduces trial activation timelines, increases patient access to experimental therapies, and has been positively received by study staff. Future projects will focus on enterprise implementation, optimization, and automation.

OBJECTIVES/SPECIFIC AIMS: Dopamine transporter (DAT1) gene variation is associated with reward-related phenotypes including alcohol response. There is also evidence for a potential moderating role for mu-opioid receptor (OPRM1) gene variation on the relationship between DAT1 variation and alcohol response measures. We aimed at studying the interaction between the DAT1 VNTR and OPRM1 A118G polymorphisms on alcohol consumption and subjective responses among non-dependent drinkers. METHODS/STUDY POPULATION: We employed a progressive ratio (PR) paradigm of intravenous alcohol self-administration (IV-ASA) using the Computer-Assisted Infusion System (CAIS) to assess the motivation for alcohol seeking and consumption in a sample of nondependent drinkers. We used the Drug Effects Questionnaire (DEQ) and Biphasic Alcohol Effects Questionnaire (BAES) to assess subjective response. IV-ASA measures included average breath alcohol concentration (BrAC) and total ethanol infused. Peripheral blood samples were collected for genotyping. Ethics approval was obtained from the NIH Addictions Institutional Review Board. RESULTS/ANTICIPATED RESULTS: Fifty participants completed the PR IV-ASA session after informed consent. There were significant interactions between the DAT1 and OPRM1 genotypes in subjective effects of alcohol. Simple main effects analysis showed that DAT1 10a allele carriers that were also OPRM1 G allele carriers had significantly higher scores for several measures: “feel the drug effects” (F (1,46)=6.573, P = 0.014), “feel intoxicated”(F(1,46)=8.613, P = 0.005) and “feeling high” (F(1,46)=10.889, P = 0.002) in DEQ and higher sedation (F(1,46)=4.575, P = 0.038) in BAES. The genotypes statistically significantly predicted average breath alcohol (F (1,61) =3.295, p=0.044) and total ethanol infused(F(1,61)=3.632, p=0.032. DAT1 VNTR and OPRM1 A118G polymorphisms taken together accounted for 6.9 and 7.8% of variations in average breath alcohol and total ethanol infused respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Polymorphic variations in DAT1 and OPRM1 interact with each other in determining subjective effects of alcohol in intravenous alcohol infusion assessing motivation for alcohol seeking and consumption in nondependent drinkers. These epistatic interactions in subjective effects of alcohol are salient in the context of predicting and understanding neurobiological effects of alcohol and thereby the therapeutic responses in treating alcohol use disorders.

Objectives/Goals: Hearing loss (HL) can result from environmental and genetic factors. Some genetic variants may be more prevalent in populations living in geographic or cultural isolation. This study explores the genetic variants associated with HL in Puerto Rico and correlates these with auditory and balance disorders to uncover novel variants. Methods/Study Population: After obtaining individual informed consent and assent for a minor when applicable, we will collect clinical audiological data and biological samples (n  =  600) from families across Puerto Rico with a history of severe to profound HL. Genomic DNA will be extracted, and exome and mitochondrial genome sequencing will be conducted to identify causal variants in genes associated with HL. The study will assess the prevalence of both novel and reported variants in genes associated with HL and investigate founder variants in the Puerto Rican population. Involvement of genes so far not associated with HL will also be considered when a genetic diagnosis cannot be established. Auditory phenotypes will be correlated with genetic findings, allowing for a comprehensive analysis of genetic contributions to HL in this population. Results/Anticipated Results: This research will advance understanding of the genetic causes of HL in Puerto Rico, leading to more accurate diagnoses, personalized treatment options, and the discovery of novel genes associated with HL. It will also serve as an evidence-based reference to analyze the adequacy of current neonatal hearing screening protocols in PR. Recruitment and sample collection have begun, and we expect our findings to uncover population-specific variants. These results will provide a foundation for further genetic studies aiming at identifying the causes of HL in Puerto Ricans regardless of age of onset. Discussion/Significance of Impact: This study will enhance our understanding of hereditary HL and serve as a basis for developing population-specific diagnostic tools and interventions, particularly in the Puerto Rican population. The research will support future genetic studies and address health disparities in HL in the island.

Objectives/Goals: Osteoarthritis (OA) is a multifactorial disease where sustained gut inflammation is a continued source of inflammatory mediators driving degenerative processes in joints. The goal was to use spontaneous equine model to compare fecal and leukocyte microbiome and correlation to transcriptome in OA. Methods/Study Population: Seventy-six horses (31 OA, 45 controls) were enrolled by population-based sampling. Feces and peripheral blood mononuclear cells (PBMC) were collected. Horses were determined to have OA by clinical and radiographic evidence. Horses were excluded if they received medications or joint injections within two months. Fecal and circulating leukocyte bacterial microbial 16s-seq was performed. Bulk RNAseq of PBMC was performed by the Illumina platform. Gene expression data were mapped to the equine genome, and differential expression analysis was performed with DESeq2. Qiime2 was used for microbial analysis. Enrichment analysis was performed with a cluster profiler. Correlation analyses were performed between the datasets. Results/Anticipated Results: Beta and alpha microbial diversity differed in feces and PBMC of OA vs. healthy horses. Horses with OA had an increased Firmicutes to Bacteroidetes ratio compared with controls. The fecal microbiome of OA horses had significantly higher amounts of Firmicutes Oribacterium (q Discussion/Significance of Impact: These data suggest that altered microbiome and PBMC gene expression are associated with naturally occurring OA in the translational equine model. While Oribacterium has been detected in humans with rheumatoid arthritis, its role in OA warrants further proteomic and metabolomic profiling.