Synergistic immunomodulatory effect of synbiotics pre- and postoperative resection of pancreatic ductal adenocarcinoma: a randomized controlled study

Sara Maher; Hesham A Elmeligy; Tarek Aboushousha; Noha Said Helal; Yousra Ossama; Mahmoud Rady; Ahmed Mohamed A Hassan; Manal Kamel

doi:10.1007/s00262-024-03686-6

Synergistic immunomodulatory effect of synbiotics pre- and postoperative resection of pancreatic ductal adenocarcinoma: a randomized controlled study

Cancer Immunol Immunother. 2024 Apr 25;73(6):109. doi: 10.1007/s00262-024-03686-6.

Authors

Sara Maher¹, Hesham A Elmeligy², Tarek Aboushousha³, Noha Said Helal⁴, Yousra Ossama⁵, Mahmoud Rady⁶, Ahmed Mohamed A Hassan⁷, Manal Kamel⁸

Affiliations

¹ Lecturer of Immunology, Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt. Saram6756@gmail.com.
² Associate Professor of General Surgery, Surgery Department, Theodor Bilharz Research Institute, Giza, Egypt.
³ Professor of Pathology, Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt.
⁴ Associate Professor of Pathology, Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt.
⁵ Lecturer of Pathology, Pathology Department, October 6 University, Giza, Egypt.
⁶ Lecturer of Surgery, Department of Surgery, Theodor Bilharz Research Institute, Giza, Egypt.
⁷ Professor of Surgery, Surgery Department, Theodor Bilharz Research Institute, Giza, Egypt.
⁸ Professor of Immunology, Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a highly immunosuppressive microenvironment. This single-blind, randomized study aimed to evaluate the synergistic immunomodulatory effects of synbiotics (probiotics and inulin prebiotics), as well as their impact on postoperative complications and outcomes, compared to the use of probiotics alone. Ninety patients diagnosed with PDAC were enrolled and randomly assigned into three groups: the placebo group, the probiotics group (receiving a mixture of ten strains of Lactobacillus, Bifidobacterium, and Streptococcus bacteria at a dose of 25 billion CFUs), and the synbiotics group (the same probiotics along with inulin prebiotics). The interventions were administered for 14 days before the surgery and continued for one month postoperatively. Tumor tissue infiltration of CD8 + T cells and the expression of IFN γ were assessed by immunohistochemistry (IHC). Inflammatory cytokines concentrations, including Il 1 B, IL 6, and IL 10, were evaluated as well by ELISA at various time points pre- and postoperative. Furthermore, patients were followed up after the surgery to assess postoperative short-term outcomes. Our results showed a significant elevation of CD8 + T cell proportion and IFN γ expression in the synbiotics group compared to the probiotics group (p = 0.049, p = 0.013, respectively). Inflammatory cytokines showed a significant gradual decrease in the synbiotics group compared to placebo and probiotics-treated groups (p = 0.000 for both). Administration of synbiotics and probiotics significantly decreased the rate of postoperative complications including anastomotic leakage, diarrhea, and abdominal distension (p = 0.032, p = 0.044, p = 0.042, respectively), with a remarkable reduction in bacteremia in the synbiotics group. These results revealed that this synbiotics formulation potentially enhances the immune response and reduces complications associated with surgery.Clinical trial identification: NCT06199752 (27-12-2023).

Keywords: CD8 + T cells; Pancreatic ductal adenocarcinoma (PDAC); Probiotics; Synbiotics.

Publication types

Randomized Controlled Trial

MeSH terms

Aged
CD8-Positive T-Lymphocytes / immunology
Carcinoma, Pancreatic Ductal* / immunology
Carcinoma, Pancreatic Ductal* / pathology
Carcinoma, Pancreatic Ductal* / surgery
Carcinoma, Pancreatic Ductal* / therapy
Cytokines / metabolism
Female
Humans
Male
Middle Aged
Pancreatic Neoplasms* / immunology
Pancreatic Neoplasms* / surgery
Postoperative Complications / prevention & control
Probiotics / administration & dosage
Probiotics / therapeutic use
Single-Blind Method
Synbiotics* / administration & dosage

Substances

Cytokines

Associated data

ClinicalTrials.gov/NCT06199752