Abstract Hematopoietic cell transplantation (HCT) is a potentially curative treatment for individuals diagnosed with hematological malignancies. As survival gains increase, symptom management is also being considered as an endpoint for treatment success yet there is paucity in the literature regarding biological correlates of symptoms. Pain is a major concern for patients undergoing HCT. Underlying inflammation has been suspected in the pathogenesis of symptoms including pain. Emerging evidence supports the gut microbiota (GM) as a potential pathway for the initiation of inflammation. Diet is a potentially modifiable factor demonstrating a significant impact on GM diversity and amenable to intervention. Understanding the interplay among pain, GM, and diet, particularly macronutrients, may inform the development of a targeted, dietary self-management intervention to mitigate pain symptoms in HCT patients. This investigation uses baseline data from a longitudinal descriptive study to explore associations among pain, GM composition (richness and evenness) using Shannon and Chao beta diversity indices, and macronutrients (protein, carbohydrates and fat), in 47 adults (> 18 years of age) receiving HCT for hematologic cancer. Pain was measured using the Brief Pain Inventory, GM was assessed using 16S ribosomal gene (V4 region) amplicons using Illumina MiSeq, and dietary information was collected using the Automated Self-Assessment 24-hour Dietary Assessment Tool (ASA-24). Data analysis was performed with the R ‘correlation’ package using Bayesian estimation of robust correlations and production of 95% Credibility Intervals (CI) and Bayes Factors (BF).The mean age of participants was 56.21 years + 14.67 years. Participants were diagnosed with myeloma (40%), lymphoma (29%) and leukemia (13%). The majority received autologous HCT (n=30). Macronutrient fat {r=-0.25, BF=1.72} had an inverse association with pain interference. Results provided at least anecdotal (BF > 1) support for a positive correlation between Healthy Eating Index (HEI) {r=0.21, BF=1.08}, total fat {r=0.32, BF=4.50}, carbohydrate {r=0.28, BF=2.47} and fat {r=0.32, BF=4.50}, and GM composition. Also, there was a positive association between the amount of protein {r=0.21, BF=1.03}, carbohydrate {r=0.27, BF=2.22}, and Chao Index. There was an inverse association between total HEI {r=-0.27, BF=1.87} and CRP levels. Taxonomic units {r=-0.41, BF=21.44}, Chao Index {r=-0.41, BF=20.28} and Shannon Index {r=-0.25, BF=1.47} had an inverse association with CRP level. This study associate pain, GM, and dietary macronutrients, suggesting potential GM targeted interventions. More research with larger sample size is needed to understand underlying dietary macronutrients' role in pain through GM diversity after HCT, aiming to ease symptoms and enhance survivorship. Citation Format: Elham Samami, Fan Yi, Michael Weaver, Angela Starkweather, Debra Lyon, Debra Lynch Kelly. Exploring the association among pain, gut microbiota, and dietary intake of macronutrients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 754.