1564P - Gut microbiome and metabolome are associated with the response to chemoradiotherapy in patients with esophageal cancer

Background

To explore the dynamic change of gut microbiota and metabolites and its predictive role in progression-free survival (PFS) in esophageal cancer (EC) after concurrent chemoradiotherapy (CCRT).

Methods

In this prospective study, 94 newly diagnosed EC patients were recruited. A total of 282 fecal samples were collected at 3 time points (T0, before CCRT; T1, 2 weeks after the initiation of CCRT; and T2, the end of CCRT). Gut microbiota and its metabolites were analyzed by 16S rRNA sequencing and untargeted metabolomics, respectively. Microbe-metabolite correlation networks were compared between patients in the long-PFS group (PFS ≥18.0 months) and short-PFS group (PFS <18.0 months). A random forest classifier was constructed to identify microbial signature related to PFS. Clinical and microbial factors potentially predictive of PFS were assessed in the univariate and multivariate Cox regression analysis.

Results

At baseline, there was no significant difference in the distribution of microbial species or pathway abundance between the two groups. The abundance of Bacteroidota and Acidobacteria increased, while the abundance of Firmicutes decreased after CCRT. Shannon index (P = .016) and PD index (P = .007) were significantly higher in the long-PFS group than for those in the short-PFS group at T1. These distinct changes in gut microbiota were accompanied by functional alterations in tryptophan, fatty acid, and bile acid metabolism and nucleotide biosynthesis pathways during CCRT. Further metabolomic analyses revealed that the distributions of metabolites from these four essential metabolic pathways varied in the two groups at T1. The PFS-prediction microbial signature at T1 included members of the Ruminococcus, and various strains from within the Blautia and Prevotella. The machine learning classifier based on gut microbiota and metabolites yielded an area under the ROC curve of 0.93. Multivariate analysis indicated PD index (P = .027), the abundance of Blautia (P = .033) and deoxycholic acid (P = .025) at T1 were independent predictors of PFS.

Conclusions

Gut microbiota and metabolites composition at 2 weeks after the initiation of CCRT were associated with PFS in EC. Further research is needed to confirm these results.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Fujian Cancer Hospital.

Funding

National Clinical Key Specialty Construction Program (Grant No. 2021).

Disclosure

All authors have declared no conflicts of interest.