Human microbiomes in cancer development and therapy

Abstract

Colonies formed by bacteria, archaea, fungi, and viral groups and their genomes, metabolites, and expressed proteins constitute complex human microbiomes. An increasing evidences showed that carcinogenesis and disease progression were link to microbiomes. Different organ sources, their microbial species, and their metabolites are different; the mechanisms of carcinogenic or procancerous are also different. Here, we summarize how microbiomes contribute to carcinogenesis and disease progression in cancers of the skin, mouth, esophagus, lung, gastrointestinal, genital, blood, and lymph malignancy. We also insight into the molecular mechanisms of triggering, promoting, or inhibiting carcinogenesis and disease progress induced by microbiomes or/and their secretions of bioactive metabolites. And then, the strategies of application of microorganisms in cancer treatment were discussed in detail. However, the mechanisms by which human microbiomes function are still poorly understood. The bidirectional interactions between microbiotas and endocrine systems need to be clarified. Probiotics and prebiotics are believed to benefit human health via a variety of mechanisms, in particular, in tumor inhibition. It is largely unknown how microbial agents cause cancer or how cancer progresses. We expect this review may open new perspectives on possible therapeutic approaches of patients with cancer.

Keywords: cancer therapy; carcinogenesis; microbiome; microorganism; tumor.

FIGURE 1

Human carcinogenic microbiomes and cancer. (A) Influence host cell proliferation and death. Microbiomes bind to E‐cadherins, which trigger β‐Catenin activation through polarity changes of barrier disruption or activate the β‐Catenin signaling pathway through CagA or AvrA, leading to dysregulation of cell proliferation. (B) Altering immune system activity. Microbiomes and microbial metabolism bind to inhibitory receptor TIGIT on human immune cells, drive inflammatory responses, and promote cancer immune evasion. (C) Effects on host metabolism. SCFAs, DCA, and LCA, which produced by microbiomes, promote carcinogenesis through host metabolism.

FIGURE 2

Alteration of immune system activity. (A) P. anaerobius recruited tumor‐infiltrating, promoted cell proliferation, and triggered the inflammatory response in the tumor microenvironment through the PI3K/AKT/NF‐kB signaling pathway. F. nucleatum induced lymphocyte death through the TLR4/MYD88 pathway, promoting tumor development. (B) Corynebacterium induced IL‐17 production, upregulated IL‐6, and activated the JAK/STAT3 signaling pathway to induce cell proliferation and tumor growth.

FIGURE 3

Influence on host cell proliferation and death. (A) Cytotoxin‐associated gene A (CagA) produced by H. pylori can stimulate inflammation and lead to the development of cancer. CagA induces DNA damage through host‐mediated upregulation of the production of reactive oxygen species in the cytoplasm and promotion of the DNA damage response. (B) The connection between microbial components and lung cancer can be explained by the production of metabolites. Veillonella, Prevotella, and Streptococcus bacteria induce epithelial cell transformation and promote epithelial cell transformation through activation of the PI3K and ERK signaling pathway.

FIGURE 4

Microbiome treatment for cancer. Possible therapeutic approaches for cancer include fecal microbiome transplantation (FMT), probiotics, prebiotic compounds, synbiotics, antibiotics, oncolyitc virus and nanospheres, which are processes through which the intestinal microbiome can regulate inflammation, modulate cell proliferation and apoptosis, and reduce the concentration of secondary bile acids. By activating the JAK/STAT, PI3K/AKT, Ras/MEK, and TLR2/4‐MYD88 pathways, which are involved in tumorigenesis, microbial dysbiosis and special bacteria can influence cancer development and progression. The microbes that ferment and produce SCFAs also affect cell proliferation and tumor growth. Several microbes, such as Fn, Helicobacter pylori, Fusobacterium, Staphylococcus aureus, Peptostreptococcus anaerobius, and Porphyromonas gingivalis, promote cancer progression. Other microbes, such as Lactobacillus, Bifidobacterium, Clostridium butyricum, Bacillus subtilis, Bifidobacteria, Lactobacoilli, Streptococcus thermophilus, Leptotrichia, Bacteroides thetaiotaomicron, and Faecalibacterium prausnitzii, can inhibit cancer progression.