Effect of PEGylated Liposomalization of Oxaliplatin on the Gut Microbiota in Mice

Abstract

Dysbiosis is a contributing factor in various conditions, including depressive disorder and irritable bowel syndrome. Key drivers of dysbiosis include stress exposure, chronic unbalanced diet, and exposure to certain pharmacological medications. While the platinum-based anticancer agent oxaliplatin (l-OHP) induces dysbiosis, it remains unclear whether liposomal encapsulation impacts this microbiota disruption. Here, we evaluated characteristics of the colonic microbiota in male C57BL/6J mice administered l-OHP or its PEGylated liposomal formulation (Lipo-l-OHP). On Day 7 following treatment with l-OHP or Lipo-l-OHP (total dose: 16 mg/kg), all mice developed mechanical allodynia, while those receiving l-OHP, but not Lipo-l-OHP, exhibited reduced body weight gain. On Day 7, mice treated with l-OHP or Lipo-l-OHP showed a trend toward reduced α-diversity of the colonic microbiota compared with untreated mice in a control group; however, α-diversity remained significantly higher in the Lipo-l-OHP group than in the l-OHP group. β-Diversity analysis revealed the distinct patterns in microbiota composition among the 3 groups. At the bacterial genus level, the relative abundances of unclassified Muribaculaceae spp., Lachnospiraceae NK4A136 group spp., Bacteroides spp., and Clostridium sensu stricto 1 spp. were significantly altered in the l-OHP group, but not in the Lipo-l-OHP group, compared with those in the control group. Interestingly, the abundances of unclassified Muribaculaceae spp. and Lachnospiraceae NK4A136 group spp. were positively correlated, and Bacteroides spp. was negatively correlated, with body weight changes in mice on Day 7. Collectively, our findings demonstrated that PEGylated liposomalization of l-OHP partially ameliorates l-OHP-induced dysbiosis in mice.