Cancer research and treatment · 2026
Combined Gemcitabine and Nab-Paclitaxel Treatment Restores Gut Microbiota Homeostasis in an Orthotopic Pancreatic Ductal Adenocarcinoma Mouse Model.
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Chung Yun Shin, Yoo In Ha, Kim Eun Hye, Jeong Jin-Yong, Kim Inki, Hwang Jung Jin, Kim Tae Won, Hong Seung-Mo, Jun Eunsung
Аннотация
PURPOSE: Although chemotherapy can disrupt homeostasis of gut microbiota, the role of chemotherapy affecting in gut microbiota of pancreatic ductal adenocarcinoma (PDAC) is unclear.
MATERIALS AND METHODS: We evaluated whether chemotherapy could alter the integrity of gut microbiota of PDAC-bearing mouse in vivo. Using a xenogenic orthotopic PDAC-bearing BALB/c nude mouse model by inoculation of BxPC-3-luc into the pancreas, we monitored tumor volumes and analyzed gut microbiota profiles via 16S rRNA sequencing, comparing mice systemically treated with gemcitabine/nab-paclitaxel (OC, orthotopic PDAC chemotherapy), those treated with 1× phosphate-buffered saline (ON, orthotopic PDAC non-treated), and normal controls (NC).
RESULTS: No differences were found in alpha diversity; however, phylogenetic diversity increased significantly in OC mice compared to ON mice. Phylogenetic analysis at the family level showed that abundances of Lachnospiraceae, Oscillospiraceae, and Bacteriodaceae were similar in OC and ON. However, Borkfalkiaceae and Lactobacillus significantly increased in OC compared to ON. Unclassified bacterial genera lacking formal taxonomic assignments and functional annotations, such as Clostridium, FMGN, PAC000663, and PAC001360, increased significantly in OC compared to ON. Further, a pathobiont of Escherichia increased significantly in ON compared to NC, but was depleted in OC.
CONCLUSION: This is the first study to demonstrate recovery of a partial, chemotherapy-associated shift toward a more balanced gut microbiota composition in a xenogenic orthotopic PDAC-bearing BALB/c nude mouse model after systemic chemotherapy of gemcitabine/nab-paclitaxel. Our findings provide proof-of-concept evidence that systemic chemotherapy-based approaches may be associated with amelioration of gut microbiota dysbiosis in a xenogenic orthotopic PDAC mouse model.
MATERIALS AND METHODS: We evaluated whether chemotherapy could alter the integrity of gut microbiota of PDAC-bearing mouse in vivo. Using a xenogenic orthotopic PDAC-bearing BALB/c nude mouse model by inoculation of BxPC-3-luc into the pancreas, we monitored tumor volumes and analyzed gut microbiota profiles via 16S rRNA sequencing, comparing mice systemically treated with gemcitabine/nab-paclitaxel (OC, orthotopic PDAC chemotherapy), those treated with 1× phosphate-buffered saline (ON, orthotopic PDAC non-treated), and normal controls (NC).
RESULTS: No differences were found in alpha diversity; however, phylogenetic diversity increased significantly in OC mice compared to ON mice. Phylogenetic analysis at the family level showed that abundances of Lachnospiraceae, Oscillospiraceae, and Bacteriodaceae were similar in OC and ON. However, Borkfalkiaceae and Lactobacillus significantly increased in OC compared to ON. Unclassified bacterial genera lacking formal taxonomic assignments and functional annotations, such as Clostridium, FMGN, PAC000663, and PAC001360, increased significantly in OC compared to ON. Further, a pathobiont of Escherichia increased significantly in ON compared to NC, but was depleted in OC.
CONCLUSION: This is the first study to demonstrate recovery of a partial, chemotherapy-associated shift toward a more balanced gut microbiota composition in a xenogenic orthotopic PDAC-bearing BALB/c nude mouse model after systemic chemotherapy of gemcitabine/nab-paclitaxel. Our findings provide proof-of-concept evidence that systemic chemotherapy-based approaches may be associated with amelioration of gut microbiota dysbiosis in a xenogenic orthotopic PDAC mouse model.