Increasing evidence highlights the cardinal role of gut microbiota in
tumorigenesis and
chemotherapy outcomes.
Paclitaxel (PTX), although as a first-line
chemotherapy reagent for
breast cancer, still requires for improvement on its efficacy and safety due to drug resistance and adverse effects. The present work explored the enhancement of a
polysaccharide derived from spore of Ganoderma lucidum (SGP) with PTX in a murine 4T1-breast
cancer model. Results showed that the combination of PTX and SGP displayed an improved
tumor control, in which
mRNA expression of several Warburg effect-related
proteins, i.e.,
glucose transporter 3 (Glut3),
lactate dehydrogenase A (Ldha), and
pyruvate dehydrogenase kinase (Pdk), and the metabolite profile of
tumor was evidently altered. Flowcytometry analysis revealed that the combination treatment recovered the exhausted
tumor infiltration lymphocytes (TILs) via inhibiting the expressions of immune checkpoints (PD-1 and Tim-3), while PTX alone evidently increased that of CTLA-4.
16S rRNA sequencing revealed a restoration by the combination treatment on gut microbiota
dysbiosis induced by PTX, especially that Bacteroides, Ruminococcus, and other 5 genera were significantly enriched while the
cancer-risk genera, Desulfovibrio and Odoribacter, were decreased. Moreover, spearman correlation analysis showed that abundance of Ruminococcus was significantly negative-associated with the amount of frucotose-6-phosphate within the
tumor. Collectively, the present study suggests the clinical implication of SGP as an adjuvant candidate for PTX against
breast cancer, which possibly relies on the regulation of
tumor metabolism and gut microbiota.