Bifidobacterium bifidum strains synergize with immune checkpoint inhibitors to reduce tumour burden in mice

Lee, Se‐Hoon; Cho, Sung Yup; Yoon, Young‐In; Park, Chang-Ho; Sohn, Jinyoung; Jeong, Jin Ju; Jeon, Bu Nam; Jang, Mongjoo; An, Choa; Lee, Suro; Kim, Yun Yeon; Kim, Gihyeon; Kim, Sujeong; Kim, Yun-Jae; Lee, Gwang Bin; Lee, Eun Ju; Kim, Sang Gyun; Kim, Hong Sook; Kim, Yeongmin; Kim, Hyun; Yang, Hyun Seung; Kim, Sarang; Kim, Seonggon; Chung, Hayung; Moon, Myeong Hee; Nam, Myung Hee; Kwon, Jee Young; Won, Sungho; Park, Joon Suk; Weinstock, George M.; Lee, Charles; Yoon, Kyoung Wan; Park, Hansoo

doi:10.1038/s41564-020-00831-6

Cited by 147 publications

(101 citation statements)

References 57 publications

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“…Similarly, the immunity of SPF animals, in which the gut microbiota was destroyed using broad spectrum antibiotics, is greatly affected; this influence is partially reflected by a reduction in the numbers of T and B cells in many tissues ( 5 , 6 ). Correspondingly, many gut microbes have important immunoregulatory functions: segmented filamentous bacteria can induce Th17 cells; Clostridium species can cause the accumulation of Foxp3 + regulatory T cells; Bacteroides fragilis can induce CD4 + T cell-dependent and -independent immune responses; and Bifidobacterium bifidum strains can synergize with immune checkpoint inhibitors to reduce the tumor burden ( 7 , 8 ). In this context, probiotics have become an important means for immune regulation, health maintenance, and disease prevention.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of the Immunomodulatory Effect of the Combination of Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus on Immunocompromised Rats

et al. 2021

Front. Immunol.

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Immunodeficiency is a very common condition in suboptimal health status and during the development or treatment of many diseases. Recently, probiotics have become an important means for immune regulation. The present study aimed to investigate the mechanism of the immunomodulatory effect of a combination of live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus (CBLEB), which is a drug used by approximately 10 million patients every year, on cyclophosphamide-immunosuppressed rats. Cyclophosphamide (40 mg/kg) was intraperitoneally injected to induce immunosuppression in a rat model on days 1, 2, 3, and 10. Starting from day 4, the rats were continuously gavaged with CBLEB solution for 15 days. The samples were collected to determine routine blood test parameters, liver and kidney functions, serum cytokine levels, gut microbiota, fecal and serum metabolomes, transcriptomes, and histopathological features. The results indicated that CBLEB treatment reduced cyclophosphamide-induced death, weight loss, and damage to the gut, liver, spleen, and lungs and eliminated a cyclophosphamide-induced increase in the mean hemoglobin content and GGT, M-CSF, and MIP-3α levels and a decrease in the red blood cell distribution width and total protein and creatinine levels in the blood. Additionally, CBLEB corrected cyclophosphamide-induced dysbiosis of the gut microbiota and eliminated all cyclophosphamide-induced alterations at the phylum level in rat feces, including the enrichment in Proteobacteria, Fusobacteriota, and Actinobacteriota and depletion of Spirochaetota and Cyanobacteria. Furthermore, CBLEB treatment alleviated cyclophosphamide-induced alterations in the whole fecal metabolome profile, including enrichment in 1-heptadecanol, succinic acid, hexadecane-1,2-diol, nonadecanoic acid, and pentadecanoic acid and depletion of benzenepropanoic acid and hexane. CBLEB treatment also alleviated cyclophosphamide-induced enrichment in serum D-lyxose and depletion of serum succinic acid, D-galactose, L-5-oxoproline, L-alanine, and malic acid. The results of transcriptome analysis indicated that the mechanism of the effect of CBLEB was related to the induction of recovery of cyclophosphamide-altered carbohydrate metabolism and signal transduction. In conclusion, the present study provides an experimental basis and comprehensive analysis of application of CBLEB for the treatment of immunodeficiency.

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Section: Introductionmentioning

confidence: 99%

Mechanism of the Immunomodulatory Effect of the Combination of Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus on Immunocompromised Rats

et al. 2021

Front. Immunol.

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“…Lee et al identified that B. bifidum species was significantly abundant in responder NSCLC patients, whereas A. Muciniphila and Blautia obeum were in abundance in non-responders [ 65 ]. Researchers employed murine models of syngeneic MC38 colon and Lewis lung carcinoma (LLC1) tumors to determine the potential modulation of the response to cancer therapeutics by B. bifidum .…”

Section: Microbiota and Immunotherapy In Preclinical Studiesmentioning

confidence: 99%

The Role of Gut Microbiota in Overcoming Resistance to Checkpoint Inhibitors in Cancer Patients: Mechanisms and Challenges

Bouferraa

Chedid

Amhaz

et al. 2021

IJMS

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The introduction of immune checkpoint inhibitors has constituted a major revolution in the treatment of patients with cancer. In contrast with the traditional cytotoxic therapies that directly kill tumor cells, this treatment modality enhances the ability of the host’s immune system to recognize and target cancerous cells. While immune checkpoint inhibitors have been effective across multiple cancer types, overcoming resistance remains a key area of ongoing research. The gut microbiota and its role in cancer immunosurveillance have recently become a major field of study. Gut microbiota has been shown to have direct and systemic effects on cancer pathogenesis and hosts anti-tumor immune response. Many studies have also shown that the host microbiota profile plays an essential role in the response to immunotherapy, especially immune checkpoint inhibitors. As such, modulating this microbial environment has offered a potential path to overcome the resistance to immune checkpoint inhibitors. In this review, we will talk about the role of microbiota in cancer pathogenesis and immune-system activity. We will also discuss preclinical and clinical studies that have increased our understanding about the roles and the mechanisms through which microbiota influences the response to treatment with immune checkpoint inhibitors.

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“…Through this approach, specific bacterial strains or mechanisms for enhancing the efficacy of ICIs have been studied. For example, the specific gut microbiome of nivolumab and pembrolizumab responders was identified, while the synergistic effect of anti-PD-1 and B. bifidum strains reportedly reduced cancer growth by modulating the production of IFN-γ by intensifying biosynthesis of immune-stimulating metabolites [102,113]. The development of techniques and information regarding how the microbiome interacts with ICIs have promoted the discovery of microbiota-linked biomarkers for response prediction of ICIs (e.g., indole, aldehydes, and short-chain fatty acids), which could be a promising target for precision medicine [99].…”

Section: Metabolomics and Metagenomics For Identifying Interactions Between The Microbiome And Icismentioning

confidence: 99%

The Comprehensive “Omics” Approach from Metabolomics to Advanced Omics for Development of Immune Checkpoint Inhibitors: Potential Strategies for Next Generation of Cancer Immunotherapy

Yoon

Lee

Chae

et al. 2021

IJMS

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In the past decade, immunotherapies have been emerging as an effective way to treat cancer. Among several categories of immunotherapies, immune checkpoint inhibitors (ICIs) are the most well-known and widely used options for cancer treatment. Although several studies continue, this treatment option has yet to be developed into a precise application in the clinical setting. Recently, omics as a high-throughput technique for understanding the genome, transcriptome, proteome, and metabolome has revolutionized medical research and led to integrative interpretation to advance our understanding of biological systems. Advanced omics techniques, such as multi-omics, single-cell omics, and typical omics approaches, have been adopted to investigate various cancer immunotherapies. In this review, we highlight metabolomic studies regarding the development of ICIs involved in the discovery of targets or mechanisms of action and assessment of clinical outcomes, including drug response and resistance and propose biomarkers. Furthermore, we also discuss the genomics, proteomics, and advanced omics studies providing insights and comprehensive or novel approaches for ICI development. The overview of ICI studies suggests potential strategies for the development of other cancer immunotherapies using omics techniques in future studies.

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Bifidobacterium bifidum strains synergize with immune checkpoint inhibitors to reduce tumour burden in mice

Cited by 147 publications

References 57 publications

Mechanism of the Immunomodulatory Effect of the Combination of Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus on Immunocompromised Rats

Mechanism of the Immunomodulatory Effect of the Combination of Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus on Immunocompromised Rats

The Role of Gut Microbiota in Overcoming Resistance to Checkpoint Inhibitors in Cancer Patients: Mechanisms and Challenges

The Comprehensive “Omics” Approach from Metabolomics to Advanced Omics for Development of Immune Checkpoint Inhibitors: Potential Strategies for Next Generation of Cancer Immunotherapy

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