Bifidobacterium Strain-Specific Enhances the Efficacy of Cancer Therapeutics in Tumor-Bearing Mice

Abstract

Colorectal cancer (CRC) is among the leading causes of cancer-related death in the world. The development of CRC is associated with smoking, diet, and microbial exposure. Previous studies have shown that dysbiosis of the gut microbiome affects cancer development, because it leads to inflammation and genotoxicity. Supplementation with specific microbiota induces anti-tumor effects by enhancing of anti-tumor immunity. Here, we observed that supplementation with either of two B. breve strains reduces tumor growth in MC38 colon carcinoma-bearing mice. Interestingly, only one B. breve strain boosted the efficacy of cancer therapeutics, including oxaliplatin and PD-1 blockade. Extensive immune profiling and transcriptomic analysis revealed that the boosting B. breve strain augments lymphocyte-mediated anti-cancer immunity. Our results suggest that supplementation with B. breve strains could potentially be used as a strategy to enhance the efficacy of CRC therapeutics.

The Role of Gut Microbiota in Tumor Immunotherapy

“…The intestinal microbiota is closely related to the occurrence and development of tumors, and its main mechanism may include releasing toxins to destroy the DNA of normal cells, causing gene mutations and directly leading to cell cancer [ 15 , 16 ]. For example, the E. coli PKS genome encodes the colibactin protein, and the toxin produced by the fragile enterotoxin is related to acute inflammatory bowel disease and colorectal tumors.…”

“…In addition, the intestinal microbiota can also regulate the level of chemokines and affect the penetration of CD8 + T cells, affecting the survival of patients with melanoma [ 34 ]. Supplementing Bifidobacterium Strain-Specific can enhance lymphocyte-mediated anticancer immunity to induce anticancer effects [ 16 ]. The metabolites of the gut microbiota can also have antitumor immunity activity.…”

“…The identification and functional research of these “beneficial bacteria” may be beneficial to the development of immune synergists, which are used as auxiliary intervention measures for tumor treatment [ 14 ]. For example, supplementation of Bifidobacterium strains can be used as a strategy to improve the effectiveness of PD-1 inhibitors in the treatment of CRC [ 16 ]. There is also a clinical trial that evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti-PD-1 in PD-1-refractory melanoma patients, and the results showed that 6 of 15 patients obtained clinical benefits.…”

A Perspective on the Role of Microbiome for Colorectal Cancer Treatment

“…It is important to note that despite the generally accepted notion of probiotics being a safe food adjunct, with many probiotic products being granted a ‘generally regarded as safe’ status, probiotic bacteria can translocate from the gastrointestinal tract and result in clinically significant disease [ 113 ]. In healthy subjects, probiotic bacteria generally do not result in severe disease even when they do translocate.…”

“…In healthy subjects, probiotic bacteria generally do not result in severe disease even when they do translocate. However, studies looking at immunocompromised populations suggest otherwise, with some reports of septic complications due to probiotics [ 113 ]. Additionally, there are a number of other challenges when conducting probiotic associated research.…”