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

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Maher S.; Elmeligy H.A.; Aboushousha T.; Helal N.S.; Ossama Y.; Rady M.; Hassan A.M.A.; Kamel M.

Journal: Cancer Immunology, Immunotherapy

Publisher: Springer Science and Business Media Deutschland GmbH

Publication Date: 25 April 2024

Volume / Issue: Volume 73 / Issue 6

Article No.: 109

ISSN: 3407004

DOI: 10.1007/s00262-024-03686-6

Scopus: View on Scopus

PubMed: 38662232

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Maher S., Lecturer of Immunology, Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt; Elmeligy H.A., Associate Professor of General Surgery, Surgery Department, Theodor Bilharz Research Institute, Giza, Egypt; Aboushousha T., Professor of Pathology, Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt; Helal N.S., Associate Professor of Pathology, Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt; Ossama Y., Lecturer of Pathology, Pathology Department, October 6 University, Giza, Egypt; Rady M., Lecturer of Surgery, Department of Surgery, Theodor Bilharz Research Institute, Giza, Egypt; Hassan A.M.A., Professor of Surgery, Surgery Department, Theodor Bilharz Research Institute, Giza, Egypt; Kamel M., 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). © The Author(s) 2024.

Keywords

CD8 + T cells; Pancreatic ductal adenocarcinoma (PDAC); Probiotics; Synbiotics; Aged; Carcinoma, Pancreatic Ductal; CD8-Positive T-Lymphocytes; Cytokines; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Postoperative Complications; Single-Blind Method; CD8 antigen; gamma interferon; immunomodulating agent; interleukin 1; interleukin 10; interleukin 6; inulin; placebo; probiotic agent; cytokine; synbiotic agent; abdominal distension; adult; age; anastomosis leakage; Article; bacteremia; Bifidobacterium; body mass; cancer surgery; CD8+ T lymphocyte; cell infiltration; clinical feature; comparative study; controlled study; demographics; diabetes mellitus; diarrhea; drug effect; endoscopic ultrasonography; enzyme linked immunosorbent assay; gastrojejunostomy; hepatojejunostomy; histopathology; human; hypertension; immunohistochemistry; inflammatory cell; Lactobacillus; laparoscopic surgery; lymph node metastasis; major clinical study; pancreas surgery; pancreatic ductal carcinoma; pancreaticoduodenectomy; pancreaticojejunostomy; postoperative complication; preoperative complication; protein blood level; protein expression; randomized controlled trial; sex; short term survival; single blind procedure; Streptococcus; superior mesenteric artery; immunology; metabolism; pancreas tumor; pathology

Citation Information

Scopus Citations: 21

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