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 177 publications

(165 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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“…In addition, the respond group showed higher tumor control rate in the germ-free avatar mouse model through FMT ( Matson et al, 2018 ). In a gut microbiome analysis of patients with non-small cell lung cancer who received ICI treatment, Bifidobacteirum bifidum was abundant in the gut of patients who responded to treatment ( Lee et al, 2021 ). Among them, it was confirmed that only specific B. bifidum strains enhance the effect of PD-1 blockade.…”

Section: Gut Microbiota Mediates Cancer Treatmentmentioning

confidence: 99%

“…Among them, it was confirmed that only specific B. bifidum strains enhance the effect of PD-1 blockade. Moreover, a metabolomic analysis reported that the bacteria strains were associated with increased serum L-tryptophan and IFN-γ secretion of cytotoxic T cells in mice ( Lee et al, 2021 ). In another paper, patients who responded to ICI responders had more abundance of the Ruminococcaceae family and significantly more alpha diversity, and systemic and antitumor immunity were generally elevated, indicating that intestinal microbes were directly related to ICIs ( Gopalakrishnan et al, 2018 ).…”

Section: Gut Microbiota Mediates Cancer Treatmentmentioning

confidence: 99%

The Role of Gut Microbiota in Modulating Tumor Growth and Anticancer Agent Efficacy

Kim

Lee

2021

Molecules and Cells

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An increasing number of studies have revealed an interaction between gut microbiota and tumors. The enrichment of specific bacteria strains in the intestines has been found to modulate tumor growth and influence the mechanisms of tumor treatment. Various bacteria are involved in modulating the effects of chemotherapeutic drugs currently used to treat patients with cancer, and they affect not only gastrointestinal tract tumors but also distant organ tumors. In addition, changes in the gut microbiota are known to be involved in the antitumor immune response as well as the modulation of the intestinal immune system. As a result, the gut microbiota plays an important role in modulating the efficacy of immune checkpoint inhibitors. Therefore, gut microbiota could be considered as an adjuvant treatment option with other cancer treatment or as another marker for predicting treatment response. In this review, we examine how gut microbiota affects cancer treatments.

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

Cited by 177 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 Role of Gut Microbiota in Modulating Tumor Growth and Anticancer Agent Efficacy

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