Gut microbial diversity and compositional shifts are associated with differential tumor growth rates in mice

Gut microbiota critically shape host immunity and cancer progression. However, the relationship between microbial composition and distinct tumor growth dynamics remains unclear, and whether specific commensals causally modulate tumor growth requires further validation.

Using a syngeneic B16 melanoma model, we stratified 47 mice into fast-, normal-, and low-growth groups based on longitudinal tumor trajectories. Fecal samples were collected before and after tumor inoculation for full-length 16 S rRNA gene sequencing. Microbial community diversity, composition, and discriminative taxa were analyzed using the microeco pipeline and linear discriminant analysis effect size (LEfSe). Functional validation was performed by oral administration of Ligilactobacillus_murinus to tumor-bearing mice, and tumor growth was monitored.

Tumor growth kinetics separated the mice into three distinct phenotypes. Alpha diversity was lowest in the low group at baseline but increased significantly after inoculation, surpassing the fast and normal groups. LEfSe analysis revealed pre-inoculation enrichment of Akkermansia_muciniphila in the normal group, L. murinus in the low group, and Prevotellaceae and Muribaculum_intestinales in the fast group. Following tumor challenge, the low group exhibited significant expansion of Lachnospiraceae, Ruminococcaceae, and Mucispirillum, consistent with a shift toward butyrate-producing and mucosa-associated taxa. Functional assays confirmed that oral gavage with L. murinus significantly attenuated tumor growth compared with controls.

Our study demonstrates that baseline microbial signatures not only stratify tumor growth phenotypes but also influence tumor progression. The lactate-to-butyrate microbial succession observed in the low group, coupled with direct suppression of tumor growth by L. murinus, highlights a protective microbial configuration that may enhance immune regulation. Conversely, enrichment of Prevotellaceae and Muribaculum in the fast group suggests a pro-inflammatory community permissive to tumor progression. These findings underscore the dual roles of gut microbes in shaping tumor outcomes and provide a rationale for microbiota-targeted interventions in cancer.