Abstract
Colorectal cancer (CRC) is a multifaceted disease influenced by both environmental and genetic factors. A large body of literature has demonstrated the role of gut microbes in promoting inflammatory responses, creating a suitable microenvironment for the development of skewed interactions between the host and the gut microbiota and cancer initiation. Even if surgery is the primary therapeutic strategy, patients with advanced disease or cancer recurrence after surgery remain difficult to cure. Therefore, the gut microbiota has been proposed as a novel therapeutic target in light of recent promising data in which it seems to modulate the response to cancer immunotherapy. The use of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics, and fecal microbiota transplantation, is therefore considered to support current therapies in CRC management. In this review, we will discuss the importance of host−microbe interactions in CRC and how promoting homeostatic immune responses through microbe-targeted therapies may be useful in preventing/treating CRC development.
Highlights
Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the fourth leading cause of cancer death in the world [1]
The enterotoxigenic B. fragilis (ETBF), an anaerobic bacterium found in the human intestinal microbiota, produces an enterotoxin (B. fragilis toxin, BFT), which is highly associated with CRC [21], by activating β-catenin signaling as well as the secretion of interleukin (IL)-8 in colonic epithelial cells, leading to persistent cellular proliferation [22]
All these results demonstrate how Fusobacterium nucleatum (Fn) abundance is well correlated with a lower response in advanced CRC patients to 5-FU-based adjuvant chemotherapy after radical surgery [89,90]
Summary
Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the fourth leading cause of cancer death in the world [1]. Current treatments for CRC include endoscopic and surgical local excision, downstaging preoperative radiotherapy and systemic therapy, extensive surgery for locoregional and metastatic disease, local ablative therapies for metastases, palliative chemotherapy, targeted therapy, and immunotherapy [8]. These treatments have doubled the overall survival of patients up to 3 years for advanced stages of the disease, CRC remains associated with poor prognosis and very low rates of long-term survival [9]. The mutual interaction between the gut microbiota and the host is further highlighted by its role in inducing immune maturation [14] For this reason, a CRC-associated microbial dysbiosis can alter the delicate equilibrium between the gut microbiota and the host’s immune system, contributing to cancer initiation and/or progression [15]. We will discuss the importance of gut microbiota modulation in CRC patients through dietary interventions as well as microbiome biomodulators, including anti-, pro-, pre-, and post-biotics and fecal microbiota transplantation, and how these therapeutic strategies can help in preventing/treating CRC
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