Escherichia coli on colorectal cancer: A two-edged sword

Abstract

Escherichia coli (E. coli) is a ubiquitous symbiotic bacterium in the gut, and the diversity of E. coli genes determines the diversity of its functions. In this review, the two-edged sword theory was innovatively proposed. For the question 'how can we harness the ambivalent nature of E. coli to screen and treat CRC?', in terms of CRC screening, the variations in the abundance and subtypes of E. coli across different populations present an opportunity to utilise it as a biomarker, while in terms of CRC treatment, the natural beneficial effect of E. coli on CRC may be limited, and engineered E. coli, particularly certain subtypes with probiotic potential, can indeed play a significant role in CRC treatment. It seems that the favourable role of E. coli as a genetic tool lies not in its direct impact on CRC but its potential as a research platform that can be integrated with various technologies such as nanoparticles, imaging methods, and synthetic biology modification. The relationship between gut microflora and CRC remains unclear due to the complex diversity and interaction of gut microflora. Therefore, the application of E. coli should be based on the 'One Health' view and take the interactions between E. coli and other microorganisms, host, and environmental factors, as well as its own changes into account. In this paper, the two-edged sword role of E. coli in CRC is emphasised to realise the great potential of E. coli in CRC screening and treatment.

FIGURE 1

Two‐edged sword role of E. coli. E. coli, as an opportunistic pathogen, exhibits dual roles in the promotion and suppression of CRC. The potential mechanisms include actions through metabolites, immune regulation, and biofilm formation. In terms of metabolites, the carcinogenesis of CRC is promoted by the production of colibactin, a genotoxin by E. coli, through the induction of DNA alkylation, and the intestinal vascular barrier is disrupted by the VirF produced by E. coli; bacteriocins produced by E. coli have been demonstrated to possess anticancer effects in in vitro experiments. In immune regulation, a reduction in the CD3⁺ and CD8⁺ T cells was observed in mice infected with CoPEC, while intestinal inflammation is increased; E. coli promoted the tumorigenic activity of human macrophages through the continuous induction of COX‐2 expression; the adhesion protein FimH of E. coli can induce DC maturation, potentially serving as an adjuvant for tumour immunotherapy. Regarding biofilm formation, the biofilm phenotype is closely associated with gut homeostasis and food digestion. Biofilms derived from CRC patients have been validated with tumour‐promoting effects in animal models, with E. coli being a significant colonizer within the biofilm. The research targeting E. coli holds potential for treating biofilm‐associated diseases.

FIGURE 2

E. coli varies in different populations. E. coli changes along the adenoma‐carcinoma sequence and varies in CRC, adenoma, and healthy people. The abundance of E. coli tends to increase, and the diversity tends to decrease in patients with CRC in the development of CRC.

FIGURE 3

Probiotic properties of E. coli. Based on the probiotic properties of E. coli, it can be applied to improve the treatment of CRC. E. coli has good adaptability to anoxic tumour microenvironment (TME) and great potential for gene editing. Besides, the physiological structure of E. coli peritrichous flagella and bacterial secretions facilitate its positive role in the development of CRC. Finally, E. coli can also inhibit the development of CRC through the interaction between gut flora.

FIGURE 4

A holistic view of E. coli. E. coli is a double‐edged sword, and its application needs to weigh the pros and cons (A). E. coli is involved in normal human metabolism, including the metabolism of microorganisms and organic acids. E. coli contributes to the maintenance of intestinal homeostasis and prevents infections by foreign bacteria. Bacteria‐mediated therapy involving E. coli is an emerging research approach in the adjuvant treatment of CRC. Pathogenic E. coli is involved in the metabolism of bile acids and bacterial toxins. Chronic inflammation, abnormal immune responses, and disruption of the intestinal barrier caused by pathogenic E. coli are risk factors influencing CRC. In the context of One Health, a comprehensive and integrated approach is required to study E. coli, where the interconnections between human, animal, and environmental health are considered. The holistic view of E. coli is a shield (B), which helps to amplify E. coli's strengths and narrow its weaknesses.

FIGURE 5

Current trends and perspectives in the use of E. coli in CRC. E. coli exhibits differences in abundance and genome across different populations, making it a potential candidate for CRC screening. Its inherent ability to localize solid tumours positions E. coli as a versatile platform that can be combined with other tools for CRC imaging and diagnosis. Various imaging techniques can be employed to observe and track E. coli, including optical techniques, acoustic imaging, MRI, and nuclear medicine imaging. As a promising drug delivery vector, E. coli can mitigate adverse drug reactions and resistance. E. coli‐mediated synergistic tumour therapies encompass immunotherapy, chemotherapy, and radiotherapy. These combined therapies contribute to improved treatment outcomes for CRC.