Title : Utilization of specific gut microbes and prebiotics for cancer therapy
Abstract:
Modulation of gut microbiota with natural product is emerging as a trendy therapy for cancer and analysis of non-invasive fecal and blood samples allows longitudinal analysis of treatment. For lung cancer, surgical resection of early-stage tumor and anti-PD-1/PD-L1 immunotherapy for late-stage tumor are common treatment methods. However, the response rate of anti-PD-1/PD-L1 immunotherapy needs to be improved. Recently, we have developed a high-throughput natural product cultuomics screening platform and gut microbes-based polysaccharides quality control methods. Previously, we reported the world's first preclinical research on natural product ginseng polysaccharides (GP) reshaping the gut microbiota and enhancing the efficacy of anti-PD-1 treatment in lung cancer patients. GPs increased the anti-tumor response to αPD-1 mAb by increasing the microbial metabolites valeric acid, and decreasing the ratio of Kyn/Trp, which contributed to the suppression of Treg and induction of Teff cells. Besides, the microbial analysis of patients fecal samples indicated that the abundance of Parabacteroides distasonis and Bacteroides vulgatus was higher in responders to anti-PD-1 blockade than non-responders. Subsequently, we successfully registered GP as a dietary supplement product in Macau and clinical trial is ongoing. Up to now, 10 NSCLC patients with acquired resistance to αPD-1 mAb have been recruited in the trial. Notably, significant differences were observed in the bacterial community structure of the patient gut microbiome of post-treatment versus pre-treatment. Analysis of microbial differential abundance showed that a significantly higher relative abundance of bacteria of the Bacteroides genus in patient’s post-treatment. For lung cancer surgery, sepsis-induced liver injury (SILI) is an important cause of septicemia deaths and side effect after surgery. To improve lung cancer prognosis and recovery after surgery, we discovered BaWeiBaiDuSan (BWBDS) formula promoted the growth of L. johnsonii in cecal ligation and puncture (CLP) treated mice. FMT treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects. Notably, L. johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity, increasing IL-10+ M2 macrophage production and enhancing intestinal integrity. Our findings revealed BWBDS and gut microbiota L. johnsonii as novel prebiotic and probiotic that may be used to treat SILI. The potential underlying mechanism was at least in part, via L. johnsonii-dependent immune regulation and IL-10+M2 macrophage production.
