458 Background: Microbial dysbiosis has been shown to be associated with the pathogenesis of gastric cancer (GC). However, the relationship between the GC microbiome and response to systemic therapy, such as neoadjuvant chemotherapy (NAC), is largely unknown. This study aims to explore changes in the microbiome after neoadjuvant chemotherapy, by analyzing the microbial profile of patients who received NAC and comparing differences among those with varied pathologic response to therapy. Methods: A microbiome bioinformatics pipeline using multiple next generation sequencing platforms was developed and used for analysis. GC tissue from patients who received NAC (n=101) and those who did not (n=85) were acquired at the time of surgical resection. Shannon alpha diversity plot and enrichment analyses by odds ratio were used to compare the microbial differences of the treatment cohorts. The microbial profiles of patients with pathologic response to NAC (>20% response) were characterized. Results: Of patients who received NAC, 66 (65.3%) experienced a greater than 20% response to NAC, and 35 (34.6%) demonstrated a 20% or lower response. Patients with a pathologic response to NAC were enriched for Rhizobium, Streptomyces, Comamonas, Sphingomonas, Micrococcus, Mycobacterium, Thauera, Hyphomicrobium, and Sinorhizobium (OR>4). There were no statistically significant differences in alpha diversity (p>0.05). Conclusions: Our results demonstrate that patients with a greater than 20% pathologic response to NAC have a distinct microbial enrichment compared to those with a poor pathologic response. Given the variable NAC treatment responses in GC, understanding unique microbial signatures in tumors will provide the landscape to explore key microbial contributors to GC NAC treatment response that may improve our understanding of treatment response variability among patients. [Table: see text]