Fecal Bifidobacterium Serves as a Predictor of Postoperative Recurrence After Neoadjuvant Chemotherapy in Pancreatic Cancer

TL;DR

High levels of Bifidobacterium in the gut at diagnosis may predict better outcomes after chemotherapy for pancreatic cancer.

Contribution

Identifies Bifidobacterium abundance as a potential predictor of postoperative recurrence in pancreatic cancer patients after neoadjuvant chemotherapy.

Findings

Patients with high Bifidobacterium levels had significantly better recurrence-free survival.

Multivariable analysis confirmed Bifidobacterium as a significant predictor of recurrence-free survival.

No significant association was found between Bifidobacterium and overall survival.

Abstract

To date, neoadjuvant chemotherapy (NAC) is a well-accepted therapeutic strategy for patients with resectable (R) and borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). We previously reported that the relative abundance of Bifidobacterium in the gut microbiota is associated with a more favorable pathological response to NAC in R/BR-PDAC. In the current study, we evaluated the association between pretreatment gut microbiota and postoperative prognosis in patients with R/BR-PDAC who underwent pancreatectomy after NAC.

In this prospective observational study, we analyzed 42 patients with R/BR-PDAC who underwent pancreatic resection following NAC with gemcitabine plus S-1 between 2020 and 2022 at Kansai Medical University Hospital. Stool samples were collected at PDAC diagnosis for microbiota analysis using 16S RNA gene sequences. In 19 genera accounting for ≥ 1% in relative abundance, the relationship between the microbiota profile and recurrence-free survival (RFS) and overall survival was examined using the Kaplan–Meier method and the Cox proportional hazards model.

The median postoperative observation period was 24 months. During the observation period, 23 patients (55%) experienced recurrence, and 10 patients (24%) died of PDAC. RFS was significantly favorable in patients in the high-Bifidobacterium group (relative abundance ≥ 4%) compared to patients in the low-Bifidobacterium group (<4%). Furthermore, multivariable analysis revealed high-Bifidobacterium and pathological metastasis of lymph node were significantly associated with RFS (hazard ratio 0.37; 95% confidence interval 0.14–0.97, P = .042). Regarding overall survival, there was no significant association with gut microbiota, including Bifidobacterium genus (hazard ratio 0.23; 95% confidence interval 0.03–1.50), in the multivariable analysis.

The relative abundance of Bifidobacterium in the gut microbiota at diagnosis may be a predictor of postoperative recurrence in patients with R/BR-PDAC treated with NAC.

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