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Intestinal Microbiota: A Novel Target to Improve Anti-Tumor Treatment?

ABSTRACT: Recently, preclinical and clinical studies targeting several types of cancer strongly supported the key role of the gut microbiota in the modulation of host response to anti-tumoral therapies such as chemotherapy, immunotherapy, radiotherapy and even surgery. Intestinal microbiome has been shown to participate in the resistance to a wide range of anticancer treatments by direct interaction with the treatment or by indirectly stimulating host response through immunomodulation. Interestingly, these effects were described on colorectal cancer but also in other types of malignancies. In addition to their role in therapy efficacy, gut microbiota could also impact side effects induced by anticancer treatments. In the first part of this review, we summarized the role of the gut microbiome on the efficacy and side effects of various anticancer treatments and underlying mechanisms. In the second part, we described the new microbiota-targeting strategies, such as probiotics and prebiotics, antibiotics, fecal microbiota transplantation and physical activity, which could be effective adjuvant therapies developed in order to improve anticancer therapeutic efficiency.

SUBMITTER: Villeger R

PROVIDER: S-EPMC6770123 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Intestinal Microbiota: A Novel Target to Improve Anti-Tumor Treatment?

Villéger Romain R Lopès Amélie A Carrier Guillaume G Veziant Julie J Billard Elisabeth E Barnich Nicolas N Gagnière Johan J Vazeille Emilie E Bonnet Mathilde M

International journal of molecular sciences 20190917 18

Recently, preclinical and clinical studies targeting several types of cancer strongly supported the key role of the gut microbiota in the modulation of host response to anti-tumoral therapies such as chemotherapy, immunotherapy, radiotherapy and even surgery. Intestinal microbiome has been shown to participate in the resistance to a wide range of anticancer treatments by direct interaction with the treatment or by indirectly stimulating host response through immunomodulation. Interestingly, thes ...[more]

PMID: 31533218

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Project description:BACKGROUND:A growing number of studies show that intestinal microbiota affect the therapeutic effects of antineoplastic agents. Disulfiram (tetraethylthiuram disulfide, DSF) is an old alcohol-aversion drug that has been shown to be effective against various types of cancers in preclinical studies, while few studies are carried out to explore its mechanism. METHODS:A mice model of melanoma xenograft was generated and treated with antibiotics (Abx), disulfiram/copper (DSF/Cu2+ ), Abx + DSF/Cu2+ , and the tumor volume and survival curve were observed. Hematoxylin-eosin (HE) staining and western blotting (WB) were used to observe the protein changes related to cell morphology, inflammation, and apoptosis in tumor tissues. Quantitative real time polymerase chain reaction (qPCR) was used to detect the expression of pro-inflammatory cytokines in tumors. High-throughput sequencing was used to detect the effects of Abx and DSF/Cu2+ on intestinal microbiota. RESULTS:The DSF/Cu2+ and Abx + DSF/Cu2+ markedly delayed tumor progression and prolonged mice survival, of which the combination of Abx and DSF/Cu2+ possessed the best anti-tumor effect. Abx + DSF/Cu2+ significantly reduced the pro-inflammatory cytokines Interleukin-1? (IL-1?), IL-6 and tumor necrosis factor ? (TNF-?) in tumors, and significantly reduced the expression of phosphorylated-protein kinase B (p-AKT)/protein kinase B (AKT), toll-like receptors 4 (TLR-4), and phosphorylated- nuclear factor kappa-B (p-NF?B)/NF?B in tumors. Moreover our high-throughput sequencing first indicated that the sound anti-cancer effect of Abx + DSF/Cu2+ had a strong connection with the increased abundance of intestinal beneficial bacteria Akkermansia, as well as the reduced abundance of opportunistic pathogenic bacteria Campylobacterales, Helicobacteraceae, and Coriobacteriaceae. CONCLUSIONS:The disturbed intestinal microbiota (increased abundance of opportunistic pathogens Campylobacterales, Helicobacteraceae, and Coriobacteriaceae) and the over-activated TLR4/NF-?B signaling pathway in tumor tissues deteriorated the cancer development, and the using of antibiotics is benefit to enhance the therapeutic effect of DSF on tumors via inhibiting the growth of opportunistic pathogenic bacteria.

Dataset Information

Intestinal Microbiota: A Novel Target to Improve Anti-Tumor Treatment?

Publications

Intestinal Microbiota: A Novel Target to Improve Anti-Tumor Treatment?

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