Diaphorobacter nitroreducens synergize with oxaliplatin to reduce tumor burden in mice with lung adenocarcinoma

Abstract

ABSTRACTLung adenocarcinoma (LADC) is the most common lung cancer and the leading cause of cancer-related deaths globally. Accumulating evidence suggests that the gut microbiota regulates the host response to chemotherapeutic drugs and can be targeted to reduce the toxicity of current chemotherapeutic agents. However, the effect of Diaphorobacter nitroreducens synergized with oxaliplatin on the gut microbiota and their impact on LADC have never been explored. This study aimed to evaluate the anti-cancer effects of D. nitroreducens, oxaliplatin, and their combined treatment on tumor growth in tumor-bearing mice. The composition of gut microbiota and the immune infiltration of tumors were evaluated by using 16S rRNA gene high-throughput sequencing and immunofluorescence, respectively. The inhibitory effect of the combination treatment with D. nitroreducens and oxaliplatin was significantly stronger than that of oxaliplatin alone in tumor-bearing mice. Furthermore, we observed that the combination treatment significantly increased the relative abundance of Lactobacillus and Akkermansia in the gut microbiota. Meanwhile, the combination treatment significantly increased the proportions of macrophage but decreased the proportion of regulatory T cells in the LADC tumor tissues of mice. These findings underscored the relationship between D. nitroreducens and the gut microbiota-immune cell-LADC axis, highlighting potential therapeutic avenues for LADC treatment.IMPORTANCEOxaliplatin is widely used as an effective chemotherapeutic agent in cancer treatment, but its side effects and response rate still need to be improved. Conventional probiotics potentially benefit cancer chemotherapy by regulating gut microbiota and tumor immune infiltration. This study was novel in reporting a more significant inhibitory effect of Diaphorobacter nitroreducens on lung adenocarcinoma (LADC) cells compared with common traditional probiotics and validating its potential as an adjuvant therapy for LADC chemotherapy in mice. This study investigated the impact of D. nitroreducens combined with oxaliplatin on the gut microbiota and immune infiltration of tumors as a potential mechanism to improve anticancer effects.

Keywords

• D. nitroreducens
• gut microbiota
• immune infiltration
• lung adenocarcinoma
• 16S rRNA gene sequencing