# Bacteria-Mediated Modulatory Strategies for Colorectal Cancer Treatment  
[PERSON]  
1 Musculoskeletal Research Group and Tumor Biology, Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilian-University Munich, 80336 Munich, Germany; [EMAIL_ADDRESS] (A.-L.M.); [EMAIL_ADDRESS] (A.B.)  
[PERSON]  
1 Musculoskeletal Research Group and Tumor Biology, Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilian-University Munich, 80336 Munich, Germany; [EMAIL_ADDRESS] (A.-L.M.); [EMAIL_ADDRESS] (A.B.)  
[PERSON]  
2 Faculty of Pharmacy, Comenius University, 8323 Bratislava, Slovakia; [EMAIL_ADDRESS]  
[PERSON]  
3 Department of Nursing, Shriza University of Medical Sciences, Shriza 713814336, Iran; [EMAIL_ADDRESS]  
[PERSON]  
4 Central Tehran Branch, Islamic Azad University, Tehran 19558478 al, Iran; [EMAIL_ADDRESS]  
[PERSON]  
5 Department of Microbiology, University of Mazandaran, Babolagar 4741613534, Iran; af.saf.  
activated B-cells, NF-\(\kappa\)B), leading to tumor cell proliferation and invasion [10; 11; 12; 13]. Moreover, it has been frequently shown that inflammatory bowel diseases and bowel-linked inflammation are not uncommonly associated with CRC tumor progression, highlighting the role of the gut's inflammation-protective capability [14].  
The gut, as a tissue hosting approximately \(3\times 10^{13}\) colonic bacteria, is assumed to be responsible for the majority of known microbial immunomodulatory effects and immunity in the intestinal tract as well as for metabolism and inflammation and even shows cancer-protective properties [15; 16; 17; 18; 19]. This effect has already been discovered in the late 1800 s by [PERSON], who was able to demonstrate tumor reduction and extended survival of CRC patients by using a mix of bacterial species _Serratia marcescens_ and _Streptococcus pyogenes_ for the treatment of sarcomas [20].  
Today, bacterial therapy has been rediscovered as a potential treatment strategy for CRC [18; 21; 22; 23], especially because tumor cells are capable of genetic mutations, and are thus able to escape from immune monitoring and can even develop resistance to standard immunotherapies. Moreover, current anti-tumor therapeutics are associated with high toxicity to normal cells, finally leading to severe side effects in patients, thus current cancer treatment is frequently exposed to a number of drawbacks [16; 24; 25]. Therefore, using bacteria strains possessing anti-cancer properties represents a promising strategy as preventative, concomitant or alternative treatment of CRC [18; 20; 21; 22; 23].  
In particular, bacterial peptides, including toxins, show characteristics such as low molecular weight and hydrophobicity, facilitating their entry into tumor tissue, where they can unfold their anti-cancer effects [26]. Furthermore, taking advantage of the fact that some bacteria show tumor targeting specificity, they have also been used as carriers for anti-tumor agents and even for tumor and metastases detection in previous studies [27; 28; 29; 30; 31]. Besides, using bacteria as probiotics has been presented as another application strategy in the treatment of CRC and its prevention, showing direct effects by suppressing carcinogens and stimulating immune modulation [32; 33; 34; 35]. This demonstrates again the various methods of bacterial application in CRC treatment approaches and its anti-cancer potential on various levels.  
In this review, we will present a wide range of recently demonstrated treatment methods using bacteria for cancer therapy, whereby different bacterial mechanisms and their properties for treatment application will be described with a focus on CRC.