**4. What is a microbiome?**

Human surfaces and cavities are populated by numerous microbial communities, like bacteria or fungi, which form a complex interactive network between themselves and the host. The gastrointestinal microbiota is estimated to contain over 1000 different phylotypes with a microbial gene catalog of 3.3 million genes [20], but it can be divided into four main categories: *Firmicutes*, *Bacteroides*, *Actinobacteria*, and *Proteobacteria* [21]. These agents play an indispensable role in human health, as they interact with the immune system, maintain epithelial homeostasis, metabolize indigestible polysaccharides, modulate the intestinal motility, regulate the luminal pH, and exclude potential pathogens from the human gut [22]. The disruption of intestinal microbial equilibrium has the capacity to alter the homeostatic network, thereby eliciting deleterious host responses as observed in inflammatory bowel disease and CRC. The dysbiosis refers to perturbations in microbial populations [23].

Wong et al. proved that intestinal microbiota has an important role in CRC carcinogenesis. Mice fed with stool from patients with CRC had a higher rate of high-grade dysplasia than the mice fed with stool from healthy controls, suggesting that human commensals may not be tumorigenic [24]. Bacteria may contribute to CRC in several ways: they can break the mucus layer and adhere to intestinal mucosa and deliver virulent proteins and molecules that will initiate oncogenic signaling in epithelial cells. As so, they can induce DNA damage leading to tumor initiation. On the other hand, bacteria can trigger procarcinogenic signaling and inflammatory microenvironment, such as IL-17 production or excessive Wnt or Stat3 signaling [25].

Some studies have identified several bacteria that can promote carcinogenesis by different mechanisms: *Escherichia coli* can cause direct DNA damage such as crosslinks and double-strand breaks due to the colibactin toxin produced by it [26], *Fusobacterium nucleatum* can produce FadA adhesin to modulate E-cadherin/ beta-catenin signaling [27], *Peptostreptococcus anaerobius* can induce cell proliferation through toll-like receptor 2 and toll-like receptor 4 pathways [28], *Bacteroides fragilis* produces a toxin that activates Wnt and NF-kB pathways which induce a pro-inflammatory state [29], and *Streptococcus gallolyticus* induces tumor growth through enhancement of inflammatory signals including cyclooxygenase-2 [30].

Xu et al. compared normal tissue with adenomas and adenocarcinomas and concluded that the microorganisms are different between the three entities. In the

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*Immunoscore and Microbiome in Colorectal Cancer: What's New?*

selective microenvironment in proximity to diseased tissue [32].

**5. Clinical applications of microbiome analysis**

cancer group, 20 biomarkers were identified: *Bulleidia*, *Catonella*, *Clostridium*, *Dialister*, *Granulicatella*, *Lactobacillus*, *Mogibacterium*, *Oscillospira*, *Parvimonas*, *Peptostreptococcus*, *Streptococcus*, *Odoribacter*, *Paraprevotella*, *Porphyromonas*, *Prevotella*, *Fusobacterium*, *Leptotrichia*, *Campylobacter*, *Desulfovibrio*, and

Even in the same individual, there are differences between normal and disease tissue sites. One study compared cancerous tissue with matched healthy tissue, and the microbial diversity was significantly lower in tumor tissue, suggesting a more

Some studies stablish a relationship between the microbiota and the cancer therapy efficacy. Iida et al. showed that microbiota leads to enzyme expression required for optimal chemotherapy activity with oxaliplatin [18]. Guthrie et al. demonstrated that inhibition of microbial ß-glucuronidase increases the adverse effects of irinotecan in some patients [33]. Concerning immunotherapy, a great number of bacteria were observed having great clinical response to immunecheckpoint therapy (by activating CTLA-4 and PD1 expression or promoting T-cell

Nevertheless, the main application nowadays is the fecal microbiota transplantation. This procedure consists in the administration of fecal bacteria from a healthy donor (without cancer, an autoimmune or metabolic disease) to a recipient by enema, colonoscopy, or enteric tube. The main objective is to alter the recipient's microbiota composition, and it is performed in a variety of diseases like *Clostridium difficile* infection, irritable bowel syndrome, inflammatory bowel diseases, obesity, multiple sclerosis, and type 2 diabetes mellitus [35]. Unfortunately, the lack of evidence and clinical trials bounds their use in clinical practice of oncologic patients. Another potential application is through oral probiotics. Probiotics are supple-

ments with live bacteria that promote gut health. Some experimental models presented a reduction rate of colorectal cancer development with their consump-

Some dietary compounds may reach the colon by several reasons: they could be too large to be absorbed in the small intestine, they could escape the deglycosylation and absorption in the small intestine, and they could not be accessible to the host due to the mixture of food. The dietary compounds that are absorbed in the small intestine could reach the colon by enterohepatic circulation [37]. Dietary bioactives can modify the carcinogenic process in several ways: by a direct or microbe-independent pathway and by an indirect or microbe-dependent pathway that include modifications in the substrates that alter the colonic microbiota or their metabolites [38]. The dietary fiber goes through the small intestine into the cecum and proximal colon where they are metabolized by the colonic microbiota and short-chain fatty acids are produced [39]. The most abundant short-chain fatty acids in the colon are acetate, propionate, and butyrate, and their concentrations typically decrease from the proximal to the distal colon [40]. The advantages from consuming fibers are the dilution of carcinogens and potential tumor promoters in the intestinal lumen [41] and the fast passage of the digesta through the colon which minimize the exposition to toxic products and increase the levels of short-chain fatty acids in the distal colon [42].

*DOI: http://dx.doi.org/10.5772/intechopen.86605*

*Treponema* [31].

proliferation) [34].

tion [36].

**6. Diet**

*Immunoscore and Microbiome in Colorectal Cancer: What's New? DOI: http://dx.doi.org/10.5772/intechopen.86605*

cancer group, 20 biomarkers were identified: *Bulleidia*, *Catonella*, *Clostridium*, *Dialister*, *Granulicatella*, *Lactobacillus*, *Mogibacterium*, *Oscillospira*, *Parvimonas*, *Peptostreptococcus*, *Streptococcus*, *Odoribacter*, *Paraprevotella*, *Porphyromonas*, *Prevotella*, *Fusobacterium*, *Leptotrichia*, *Campylobacter*, *Desulfovibrio*, and *Treponema* [31].

Even in the same individual, there are differences between normal and disease tissue sites. One study compared cancerous tissue with matched healthy tissue, and the microbial diversity was significantly lower in tumor tissue, suggesting a more selective microenvironment in proximity to diseased tissue [32].
