Pancreatic cancer is one of the most lethal and chemo-resistant cancers worldwide. Growing evidence supports the theory that the gut microbiota plays an essential role in modulating the host response to anti-cancer therapy. The present study aimed to explore the effect of probiotics as an adjuvant during chemotherapy for pancreatic cancer. An LSL-Kras^G12D/−-Pdx-1-Cre mouse model of pancreatic ductal adenocarcinoma (PDAC) was created to study the effects of using four-week multi-strain probiotics (Lactobacillus paracasei GMNL-133 and Lactobacillus reuteri GMNL-89) as an adjuvant therapy for controlling cancer progression. At 12 weeks of age, pancreatitis was induced in the mice by two intraperitoneal injection with caerulein (25 μg/kg 2 days apart). Over the next 4 weeks the mice were treated with intraperitoneal injections of gemcitabine in combination with the oral administration of probiotics. The pancreas was then harvested for analysis. Following caerulein treatment, the pancreases of the LSL-Kras^G12D/−-Pdx-1-Cre transgenic mice exhibited more extensive pancreatic intraepithelial neoplasia (PanIN) formation. Combined treatment with gemcitabine and probiotics revealed a lower grade of PanIN formation and a decrease in the expression of vimentin and Ki-67. Mice that received gemcitabine in combination with probiotics had lower aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Notably, the use of high-dose probiotics alone without gemcitabine also had an inhibitory effect on PanIN changes and serum liver enzyme elevation. These findings suggest that probiotics are able to make standard chemotherapy more effective and could help improve the patient’s tolerance of chemotherapy.

胰腺癌是世界上最具致死性和化学抗性的癌症之一。越来越多的证据支持这一理论，即肠道菌群在调节宿主对抗癌治疗的反应中起着至关重要的作用。本研究旨在探讨益生菌作为胰腺癌化疗期间佐剂的作用。建立了LSL-Kras ^{G12D /--} Pdx-1-Cre胰腺导管腺癌（PDAC）小鼠模型，以研究使用四周多菌株益生菌（副干酪乳杆菌GMNL-133和路氏乳杆菌）的作用GMNL-89）作为控制癌症进展的辅助疗法。在12周龄时，通过两次腹膜内注射青霉素（间隔2天25μg/ kg）在小鼠中诱发胰腺炎。在接下来的4周中，用吉西他滨腹腔注射结合口服益生菌治疗小鼠。然后收集胰腺进行分析。经青霉素处理后，LSL-Kras ^{G12D /-}的胰腺-Pdx-1-Cre转基因小鼠表现出更广泛的胰腺上皮内瘤变（PanIN）形成。吉西他滨和益生菌的联合治疗显示较低水平的PanIN形成，波形蛋白和Ki-67的表达降低。接受吉西他滨联合益生菌治疗的小鼠的天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）含量较低。值得注意的是，单独使用不含吉西他滨的大剂量益生菌也对PanIN变化和血清肝酶升高具有抑制作用。这些发现表明，益生菌能够使标准化疗更加有效，并且可以帮助提高患者对化疗的耐受性。