Fecal, duodenal, and tumor microbiota composition of esophageal carcinoma patients, a longitudinal prospective cohort

The microbiome has been associated with chemotherapy and immune checkpoint inhibitor efficacy. How this pertains to resectable esophageal carcinoma is unknown. Our aim was to identify microbial signatures in resectable esophageal carcinoma associated with response to neoadjuvant chemoradiotherapy with or without an immune checkpoint inhibitor. From 2 prospectively collected esophageal carcinoma cohorts (n = 172 in total) treated with neoadjuvant chemoradiotherapy alone (n = 132) or a combination of neoadjuvant chemoradiotherapy and an immune checkpoint inhibitor (n = 40), fecal samples were available at baseline, during treatment, and presurgery. Additionally, in the immune checkpoint inhibitor-treated patients, tumor and duodenal snap frozen biopsies were collected over time. Fecal, tumor, and duodenal DNA were extracted for 16S ribosomal RNA sequencing. Associations were investigated between microbiome composition pathological complete response and progression-free survival (PFS). There was a statistically significant shift in the microbiota profile of the fecal, tumor, and duodenal microbiota over time. In the total cohort, patients with a pathological complete response had a stable fecal alpha diversity, while the diversity of poor responders decreased during treatment (P = .036). Presurgery, lower alpha diversity (