# Bacteria-Mediated Modulatory Strategies for Colorectal Cancer Treatment
## 2 Bacterotherapy in CRC Treatment
### Mechanisms Used in Bacterotherapy in CRC
#### 2.1.6 Maintaining Microbial Equilibrium  
When the microbial equilibrium is disrupted, pathogenic microorganisms may be prevalent in the gut, potentially leading to the pathogenesis of CRC. Therefore, altering the bacterial composition and reestablishing, if disrupted, the critical balance between different bacteria species could represent a new therapeutic approach helping to treat CRC [34]. The role of microbiota in the development of CRC has increasingly emerged since several studies found significant differences in the composition of the intestinal microbiome between CRC patients and healthy individuals, whereas specific microbes and bacterial strains that are enriched in CRC pathogenesis could be, at least in part, identified [121; 122]. In general, CRC patients often show a reduced microbial diversity compared to healthy individuals, whereas bacterial strains including _Streptococcus bovis_, _Helicobacter pylori_, _Bacteroides fragilis_, _Enterococcus faecalis_, _Clostridium septicum_, _Fusobacterium_ spp. and _Escherichia coli_ are suspected to play a critical role in carcinogenesis of CRC [121; 123; 124; 125]. It is assumed that these specific bacteria trigger CRC by different mechanisms, such as increased release of bacterial toxins and pro-carcinogenic compounds leading to mutagenesis, reduced bacterial synthesis of health-beneficial metabolites, destruction of the epithelial barrier and microbiotic alterations and dysbiosis, which finally promote abnormal immune activity leading to chronic inflammation, stimulating CRC development and progression [126; 127; 123]. Although it is still not fully understood if the disruption of microbial balance and dysbiosis acts as a cause or consequence of CRC tumorigenesis and which factors interact with each other and contribute to CRC development, the model of bacteria-induced CRC mechanisms has greatly contributed to finding new options in CRC therapy. These approaches include the supplementation of inflammation-protective microbial fermentation products, elimination and suppression of bacteria-released toxins with inhibitor molecules, enhancing anti-tumor treatment efficiency by using specific bacteria such as Bifidobacterium, as well as consumption of probiotica [123]. Probiotics have the ability to direct cells into a vital state by modulating the immune system, lowering blood cholesterol and decreasing colitis [35], whereby each probiotic has a distinct function that could be beneficial for CRC prevention [35]. For example, probiotics have been shown to play a pivotal role in reducing pro-inflammatory cyclooxygenase-2 expression, which is involved in tumor angiogenesis, hence contributing to carcinogenesis suppression [128]. In addition, anti-inflammatory properties of probiotics were also shown by the down-regulation of the master regulator of inflammation NF-kB and its associated signaling pathways. This further highlights the major potential of probiotics in reducing inflammation through NF-kB modulation and thus preventing inflammation-associated diseases such as CRC [44; 45; 128; 129]. Moreover, [PERSON] et al. showed the great impact of probiotics on increasing the anti-cancer activity of anti-PDL1 medicine [130], demonstrating that intestinal bacteria can remarkably affect both immunotherapy and chemotherapy in order to promote anti-cancer effects. Moreover,_Lactobacillus acidophilus_ represents another probiotic species that has been shown to reduce the occurrence of colorectal tumors as well as the size of tumors in mice, whereby the bacteria has been discovered to have anti-cancer effects through enhancing serum levels of IFN-, IL-10 as well as the number of CD4+ and CD8+ cells, while drastically lowering serum levels of CEA and CA19-9 tumor markers [33]. In addition, _Lactobacillus brevis_ SBL8803, which has been identified in fermented malt, was also shown to exhibit anti-colon cancer properties. Hereby, polyphosphate actin as an anti-cancer chemical is produced by _L.