Advances in intestinal flora for the development, diagnosis and treatment of CRC

Abstract

Colorectal cancer (CRC), being prevalent among digestive tract malignancies, exhibits substantial mortality and morbidity rates. The intestinal microbiota, predominantly located in the colorectum, is diverse and comprises both conditionally pathogenic bacteria that can promote CRC development and probiotics that can inhibit it to some extent. Intestinal flora is associated with colorectal cancer, affecting its onset and progression through metabolites, immune regulation, and damage to the intestinal mucosal barrier. The intestinal flora exhibits significant potential in the diagnosis and treatment of CRC. Certain bacterial species can serve as biomarkers for CRC, aiding in the detection of precancerous and early-stage lesions. For instance, alterations in the abundance of Fusobacterium nucleatum (Fn) and Enterotoxigenic Bacteroides fragilis (ETBF) may indicate an elevated risk of CRC. On the other hand, probiotics such as Bifidobacteria could modulate chemotherapy and immunotherapy, improving treatment outcomes and reducing side effects, making them an effective approach to prevent CRC etiology and act as an adjuvant therapy. This paper focuses on a review of the relationship between intestinal flora and CRC, sorting out its potential role in developing, diagnosing, and treating CRC. It will advance precise, intelligent, and individualised prevention and treatment for CRC.

Keywords: colorectal cancer; intestinal flora; pathogenesis; prevention and treatment; screening.

Figure 1

Two main mechanisms of Fn promoting CRC proliferation. CK1, Casein Kinase 1; GSK-3, Glycogen Synthase Kinase – 3; FZD, Frizzled receptors; Dvl, Dishevelled; APC, Adenomatous polyposis coli; CBP, CREB-binding protein; TLR4, Toll-like receptor 4. (A) FadA on the surface of Fn adheres to E-cadherin on the surface of host cells, triggering the Wnt / β-catenin signaling pathway. Wnt ligands bind to Frizzled receptors and form complexes with LRP5 / 6 on the cell surface to activate signal transduction. Subsequently, Dvl is phosphorylated and activated, leading to the inactivation of GSK-3, thereby preventing the degradation of β-catenin. β-catenin accumulates and transports into the nucleus, binds to the LEF / TCF transcription factor in the nucleus, activates the expression of Wnt target genes, and promotes the proliferation of CRC cells. (B) Fn activates the host cell’s TLR4 receptor through its LPS, initiating the NF-κB signaling pathway, which leads to an increase in the levels of miR-21. The upregulation of miR-21 suppresses the expression of RASA1, thereby relieving the suppression of the RAS signaling pathway and resulting in its activation. The activated RAS signaling pathway propels the cell cycle into the S phase, promotes DNA synthesis, and enhances the proliferation of CRC cells. This figure was drawn by Figdraw.