Cancer invasion and anaerobic bacteria: new insights into mechanisms

Abstract

There is growing evidence that altered microbiota abundance of a range of specific anaerobic bacteria are associated with cancer, including Peptoniphilus spp., Porphyromonas spp., Fusobacterium spp., Fenollaria spp., Prevotella spp., Sneathia spp., Veillonella spp. and Anaerococcus spp. linked to multiple cancer types. In this review we explore these pathogenic associations. The mechanisms by which bacteria are known or predicted to interact with human cells are reviewed and we present an overview of the interlinked mechanisms and hypotheses of how multiple intracellular anaerobic bacterial pathogens may act together to cause host cell and tissue microenvironment changes associated with carcinogenesis and cancer cell invasion. These include combined effects on changes in cell signalling, DNA damage, cellular metabolism and immune evasion. Strategies for early detection and eradication of anaerobic cancer-associated bacterial pathogens that may prevent cancer progression are proposed.

Keywords: aggressive cancer; anaerobic bacteria; bacterial invasion; cancer; infection; intracellular bacteria; mechanisms; metastases; pathogenic; polymicrobial.

Fig. 1.. The seven steps for how human cell invasive pathogenic bacterial species may cause cancer and invasion. The key bacteria involved are included in the legend, other bacteria may be involved at specific steps as discussed in the text and detailed in Table 1, including Sneathia spp., Prevotella spp. and Veillonella spp. Early events of effects of cancer associated bacteria steps 1 to 3, proposed later events of cancer-associated bacteria steps 4 to 7 (also including step 2). The detailed mechanisms of action of the anaerobic bacteria causing host cell and tissue changes associated with carcinogenesis and cancer cell invasion and the proposed order of events are described, several of the mechanisms in the steps are strongly supported by evidence and some are hypotheses, as described in further detail below in the review main text, steps 1 to 7.

Fig. 2.. Step 5A, potential mechanisms of action of human cell invasive intracellular pathogenic bacterial species on host cell glycine metabolism and associated pathways. hCYS: homocysteine; MET: methionine; meTHF: 5,10-methylenetetrahydrofolate; MS: bacterial methionine synthase; mTHF: 5-methyltetrahydrofolate; MTHFR: bacterial methylenetetrahydrofolate reductase; SAH: S-adenosylhomocysteine; SAM: S-adenosylmethionine; THF: tetrahydrofolate; ThyX: bacterial thymidylate synthase. Impacts of specific bacteria on the host cell glycine metabolism and associated pathways are as indicated with the symbolized images of the bacteria displayed in the Fig. 2 key legend. Bacterial enzyme activities and enzyme complexes are detailed (i) to (v) above and in the review main text.

Fig. 3.. Summary overview of steps 1 to 7 and the interlinked mechanisms of how multiple invasive anaerobic bacteria may cause cancer and cancer progression. The key bacteria involved are included in the legend, other bacteria may be involved at specific steps as discussed in the text and detailed in Table 1, including Sneathia spp., Prevotella spp. and Veillonella spp.