Gut microbiota dysbiosis induced by brain tumors modulates the efficacy of immunotherapy
Hyeon Cheol Kim, Hyun-Jin Kim, Jeongwoo La, Won Hyung Park, Sang Hee Park, Byeong Hoon Kang, Yumin Kim, Heung Kyu Lee
Abstract
Although the influence of gut microbiota on various tumors has gained recognition, the intricate mechanisms underlying its effects on brain tumors remain largely unexplored. Our study aims to discover crucial gut microbiota that significantly bolster the immune response against brain tumors. Employing a murine model, we utilize 16S rRNA sequencing to analyze the evolution of gut microbiota alongside tumor progression, and we intervene with dietary adjustments using tryptophan to restore microbiota alterations. Tryptophan supplementation not only reverses these microbial changes but also significantly enhances survival by boosting T cell circulation and improves the efficacy of immunotherapy. Among the microbial species that respond positively to tryptophan, Duncaniella dubosii emerges as a pivotal contributor, replicating tryptophan's immunomodulatory effects. This study underscores the potential of targeting gut microbiota to enhance immunotherapy efficacy, particularly through mechanisms involving T cell modulation.