Colorectal cancer (CRC) is one of the causes of cancer-related mortalities across the globe. Epidemiological studies reveal the risk factors for CRC are genetic and environmental factors. The current therapeutic methods for CRC are associated with side effects and drug resistance. Gut microbiome therapy is one of the recent approaches for the prevention of CRC, reducing its progression and improving the effectiveness of colorectal cancer treatment by modulating the gut microbiome. The use of phytoconstituents is another approach. These compounds increase the gene expression of the cell cycle inhibitors and protein levels. This chapter summarizes the role of the gut microbiome and modification of the gut microbiota to improve treatment efficacy and minimize adverse effects of CRC therapies. Natural candidates like gut microbes and plant-derived bioactive components demonstrate their efficacy in appropriate in vivo models and clinical studies, which may lead to the discovery of alternative therapies for colorectal cancer.
TopIntroduction
Carcinogenesis is a multistage process consisting of initiation, promotion, and progression phases involving sequential generations of cells that exhibit continuous disturbance of cellular and molecular signal cascades (Rajamanickam & Agarwal, 2008). Cancer is a disease in which some cells of the body proliferate uncontrollably, multiplies incessantly, form tumor, spread to other regions of the body, and encourages growth of blood vessels to obtain nutrients. A tumor can be of two types, malignant and benign. Malignant tumors are more dangerous that can easily metastasize by entering into the blood circulation or lymphatic system. Whereas, a benign tumor can grow but restricted to one area and will not spread (Pandurangan et al., 2016). These changes are caused by both genetic and environmental factors and usually take years to develop.
There are more than 120 different types of cancers. Among them colorectal cancer (CRC) is one of the most common types of cancers in humans and is closely linked to the global cancer-related mortalities worldwide. Figure 1 shows the stages of colorectal cancer. Signs and symptoms of the disease may include blood in the stools, changes in bowl movement, weight loss and fatigue.
Figure 1. Stages of Colorectal cancer (Courtesy by biorender.com)
Prevention of CRC usually depends on screening methods to diagnose adenomatous polyps which are precursor lesions to colon cancer. The present treatment for colon cancer is generally based on using cytotoxic drugs, radiotherapy, chemotherapy, and surgery. Apart from these treatments, natural products are also used for the treatment and control of colon cancer progression (Aiello et al., 2019).
Intestinal dysbiosis plays an important role in CRC development. The gut microbiota contain a large population of microorganisms that interact directly with host intestinal cells and can affect immunity and metabolic activities in the gastrointestinal tract (Guinane & Cotter, 2013). Significant changes in composition and quantity of specific bacteria can be detected in patients with CRC and might use as biomarkers for disease screening, prognosis and to predict its response to treatment (Villéger et al., 2018). Different approaches including prebiotics, probiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT) have been used to implement gut microbiome (Kaźmierczak-Siedlecka et al., 2021). These approaches show promising results, arbitrarily by correcting microbiome composition, regulate innate immune system, preventing pathogen colonization and exerting selective cytotoxicity against tumor cells (Fong et al., 2020).
Throughout history, natural products or herbal drugs have played important role in the treatment of human ailments. The crucial role played by natural products from medicinal plants in the discovery and development of novel anti-colon cancer agents (Benarba & Pandiella, 2018). Historically, plants have been rich sources of natural product drug discovery, and in the anticancer area. Plant-derived product, such as vincristine, etoposide, paclitaxel, docetaxel, topotecan, and irinotecan, are among the most effective cancer chemotherapeutics currently available (Cragg & Pezzuto, 2016).
The potential of natural compounds such as flavonoids, anthocyanins, alkaloids, carotenoids, and terpenoids for cancer prevention has been widely investigated (Câmara et al., 2021). So many shreds of evidence supporting that moderate consumption of fruits and vegetables are correlated with decreased risk of CRC (Liang & Binns, 2009). Some natural compounds have the ability to modulate signalling pathways as well as to regulate the expression of genes involved in cell cycle regulation, differentiation, and apoptosis. As wellbeing useful in the prevention, some of these molecules could be also helpful for the treatment of CRC (Redondo-blanco, 2017). There is a resurgence of interest in natural products such as medicinal plants and their extracts as an alternative solution to curing CRC (Graziani et al., 2018).