Oral Lactobacillus Rhamnosus is Associated with Pancreatic Tumor Growth and Reduced T-Cell Infiltration in Mice

Background: Lactobacillus species are widely used as probiotics and may influence host immunity, but their effects on tumor progression are context-dependent. Objective: To evaluate whether oral exposure to a tumor-derived Lactobacillus rhamnosus isolate is associated with pancreatic tumor growth, gut microbiota alterations, and immune changes in a mouse model. Methods: A human pancreatic tumor-derived L. rhamnosus isolate was studied in vitro and in vivo. Pancreatic cancer cell lines were treated with bacterial culture supernatant to assess proliferation and migration. C57BL/6J mice bearing subcutaneous KPC tumors received oral gavage or intratumoral injection of L. rhamnosus. Cecal microbiota was analyzed by 16S rRNA sequencing. Tumor immune infiltration was evaluated by immunohistochemistry and flow cytometry. Results: L. rhamnosus supernatant showed no significant effects on pancreatic cancer cell proliferation or migration in vitro (all p > 0.05). Oral exposure to L. rhamnosus was associated with accelerated tumor growth (1402 +/- 421 vs. 1018 +/- 348 mm & sup3;; p = 0.0239), whereas intratumoral injection showed no effect (p > 0.05). Oral exposure was also associated with reduced intratumoral CD8(+) T-cell infiltration (0.29% +/- 0.26% vs. 0.69% +/- 0.23%; p = 0.0097) and lower T helper 1 (Th1) cell proportion (1.1% +/- 0.5% vs. 3.9% +/- 2.2%; p = 0.0068). No significant differences were observed in tumor-associated macrophages, regulatory T cells, or myeloid-derived suppressor cells (all p > 0.05). Conclusion: In this mouse model, oral exposure to this L. rhamnosus isolate was associated with accelerated tumor growth, altered gut microbiota, and reduced intratumoral T-cell infiltration. Causality was not established; these findings are observational and hypothesis-generating.