Resumen de Role of intestinal microbiota composition in colorectal cancer and in the response to neoadjuvant radiochemotherapy previous to surgery
The incidence of cancer has been increasing in the last decades. Currently, colorectal cancer (CRC) is considered the second type of cancer that causes the highest mortality in the Western world. The CRC is a disease of multifactorial origin, an important factor in the increased risk of having this disorder is obesity. The intestinal microbiota has been associated with different diseases, among which are obesity and CRC, so this microbiota is assumed to be a possible link between both disorders, although the mechanisms of action are actually unknown. Due to this assumption, the composition of the fecal microbiota of patients with CRC with and without obesity was determined in comparison with the microbial profile of healthy non-obese controls, in order to unravel the possible relationship of the intestinal microbiota with the state of inflammation, intestinal permeability, and a metabolite derived from bacteria, trimethylamine N-oxide (TMAO), all in the context of obesity-associated CRC. Thus, the intestinal microbiota of patients with CRC and obesity is characterized by the presence of a greater abundance of opportunistic pathogens (such as Prevotella, Fusobacterium nucleatum, Enterobacteriaceae and Escherichia coli), which can alter the intestinal barrier function (increased levels of circulating zonulin) and can contribute to inflammatory processes related to CRC by increasing the production of inflammatory molecules such as IL-1β and TMAO. The results strongly suggest an important role for the gut microbiota in the development of CRC in obese patients.
On the other hand, radiochemotherapy treatment prior to surgery has become a standard process in the treatment of CRC. The gut microbiota has been linked to the efficacy and toxicity of cancer treatments. Bacterial dysbiosis is considered a cause of less effective treatment, greater toxicity in the patient, and a worse general prognosis and survival in patients with metastatic CRC. In the same way, radiation and cancer drugs cause alterations in the composition of the intestinal microbiota that also affect the host's response to treatment. The existence of a relationship between the intestinal microbiota (CRC difference in the composition and functionality of this microbiota) and the response to treatment with preoperative radiochemotherapy in patients with CRC, could affect clinical results and could be have an important effect on tumor regression in patients with CCR. Therefore, the identification of composition, abundance and diversity of the intestinal microbiota that is associated with the response to preoperative treatment with radiochemotherapy of patients with CRC was determined. We also compared the gut microbiota composition and their fuctions as well as the variations in concentrations of different bacterial metabolites, such as polyamines and short-chain fatty acids between patients with good response, poor response or no response to treatment.
Regarding the response to neoadjuvant radiochemotherapy in patients with CRC, no significant changes were found in the diversity and composition of the intestinal microbiota with the exception of a significant decrease in Fusobacterium, Escherichia and Klebsiella and a significant increase in Bifidobacterium at the time post-treatment compared to baseline. After classification of CRC patients into responders (R) and poor or non-responders (NR) to neoadjuvant radiochemotherapy, a significant increase in the diversity and richness of R patients compared to NR was observed , in addition to a differentiation in bacterial composition between the two groups of patients, with unfavorable pro-inflammatory bacterial taxa prevailing in the NR group, and a significant increase in probiotics and butyrate-producing bacteria in R patients. Furthermore, NR patients had significantly higher levels of some acetyl derivatives of polyamines and serum zonulin and significantly lower levels of fecal butyric acid than R patients. Suggesting that baseline intestinal composition in CRC patients is important in predicting the response of the gut microbiome to neoadyuvant radiochemotherapy.
