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The Gut Effect on Colon Cancer

 Knowing that bacteria may be causing colon cancer did not come as a surprise. It is, after all, an inevitable consequence of living in close-knit harmony (eubiosis) with our one hundred trillion microbial partners. There may come a point when that harmony is disrupted causing a reaction where we humans seem to be at the receiving end of the stick! And in this case, colon cancer appears to be the outcome.     In an article published in February 2018, the research team of Dr. Cynthia Sears discovered the bacterial culprits involved in triggering tumorigenesis in 6 patients who had familial adenomatous polyposis (FAP) or the hereditary form of colon cancer. There were no previous studies on the composition of the microbiome in hereditary colon cancer patients. The study provided information on 2 bacteria,  E.coli  and  Bacteroidesfragilis , which could penetrate the colon’s mucus layer unlike other bacteria and create a favorable environment or protective biofilms for their colonies to expand. These biofilms were located in close proximity to the colon’s epithelial cells.      Bacteroides fragilis  toxin and Colibactin ( E. coli)  were toxins found in increased quantities in FAP patients because of the increased numbers of  Bacteroides fragilis  and  Escherichia coli  bacteria. The normally benign polyps in FAP patients provided a fertile ground for the toxins where DNA mutations were generated and immune system changes occurred to cause the growth of tumors.     This theory was substantiated by a parallel study that was published in  Cell Host&Microbe . In this study, mice were injected with  Bacteroides fragilis  and the molecular activity in the tumorigenic process was analyzed. The immune system changes involved multiple players that participated in a signaling pathway. Most notably, the toxin activated inflammation-inducing STAT3, IL-17, and NF-kB. This collaboration of pro-inflammation molecules stimulates tumorigenesis. The toxin released by  E. Coli  causes mutations in DNA. The combined effect of the 2 bacteria appears to activate the tumorigenic pathway.     Based on the findings in hereditary colon cancer patients, it has been observed that almost half of sporadic colon cancer patients are infected with these 2 microbes. Not all people who have both these bacteria develop cancer. In fact, both these bacteria are found in the gut from childhood in most cases. Depending on the exposure to cancer-causing agents or changes in the colon cells, these bacteria may find a favourable environment to trigger the tumor-causing cascade of molecular events.     Incidentally, this is not the first time that bacteria have been shown to be at the root of colon cancer. Earlier in December 2017, a study published in Science provided details on a bacterium that was found predominantly in colorectal tumors.  Fusobacterium nucleatum  were found to be prevalent in local and metastatic sites of colorectal cancer. Along with  F. nucleatum , researchers found a community of bacteria that were identical and co-existed together at each tumorigenic site. So, it appears these bacteria travel with cancer cells to their metastatic destinations. So far, the exact method by which Fusobacteria cause tumorigenesis is not clear.     The science of tumorigenesis is important to understand how to tackle the disease. And so, with this fundamental discovery, there are new possibilities of treating colon cancer patients beginning at the diagnostic stage. In the era of personalized medicine, the discovery of tumorigenic bacteria helps diagnosis. Patients going through colonoscopy can be tested for the causative types of bacteria. And in the event, these patients test positive, personalized treatments, such as vaccinations or specific narrow-spectrum antibacterial drugs will be effective.     Currently, antibiotics are broad-spectrum and may actually do more harm than good by eliminating beneficial bacteria along with the tumor-causing ones. In this regard, a significant discovery was made in the first week of February 2018. Scientists appear to have devised a way of turning off the antibiotic resistance gene of cancer cells. By using near infrared laser treatment and drug-carrying nanoparticles, the efflux pumps that expel drugs and other toxins from cells, are turned off. During this period, cancer cells can be specifically targeted with chemotherapy drugs without the fear of cells becoming resistant to the drugs. This research is still in its infancy but it provides hope and optimism that treatments involving specific targeting of cancer cells where normal cells are spared, maybe just around the corner.     Perhaps in the future, there may be potential for identifying the precise bacteria causing tumorigenesis. With this exact diagnosis, a suitable treatment strategy may be devised where the precise antibiotic to target the bacteria may be utilized. In order that the drugs do not target healthy cells, markers on cancer cells that could cause drug resistance may be downregulated or silenced for a short period till the drugs achieve their target of eliminating the cancer cells. The patient is spared of losing their healthy cells and the tumor is eliminated with minimum damage to the body’s system.     Bacteria in our bodies can be a boon when they are in harmony and in the right balance. Tilting the balance can have adverse outcomes as observed in the latest research on colon cancer. The gut microbiome certainly deserves our respect. So, let us be kind to our gut as these microbes can pack a punch!  BY  Smitha Dutt

Knowing that bacteria may be causing colon cancer did not come as a surprise. It is, after all, an inevitable consequence of living in close-knit harmony (eubiosis) with our one hundred trillion microbial partners. There may come a point when that harmony is disrupted causing a reaction where we humans seem to be at the receiving end of the stick! And in this case, colon cancer appears to be the outcome.

 

In an article published in February 2018, the research team of Dr. Cynthia Sears discovered the bacterial culprits involved in triggering tumorigenesis in 6 patients who had familial adenomatous polyposis (FAP) or the hereditary form of colon cancer. There were no previous studies on the composition of the microbiome in hereditary colon cancer patients. The study provided information on 2 bacteria, E.coli and Bacteroidesfragilis, which could penetrate the colon’s mucus layer unlike other bacteria and create a favorable environment or protective biofilms for their colonies to expand. These biofilms were located in close proximity to the colon’s epithelial cells.

 

Bacteroides fragilis toxin and Colibactin (E. coli) were toxins found in increased quantities in FAP patients because of the increased numbers of Bacteroides fragilis and Escherichia coli bacteria. The normally benign polyps in FAP patients provided a fertile ground for the toxins where DNA mutations were generated and immune system changes occurred to cause the growth of tumors.

 

This theory was substantiated by a parallel study that was published in Cell Host&Microbe. In this study, mice were injected with Bacteroides fragilis and the molecular activity in the tumorigenic process was analyzed. The immune system changes involved multiple players that participated in a signaling pathway. Most notably, the toxin activated inflammation-inducing STAT3, IL-17, and NF-kB. This collaboration of pro-inflammation molecules stimulates tumorigenesis. The toxin released by E. Coli causes mutations in DNA. The combined effect of the 2 bacteria appears to activate the tumorigenic pathway.

 

Based on the findings in hereditary colon cancer patients, it has been observed that almost half of sporadic colon cancer patients are infected with these 2 microbes. Not all people who have both these bacteria develop cancer. In fact, both these bacteria are found in the gut from childhood in most cases. Depending on the exposure to cancer-causing agents or changes in the colon cells, these bacteria may find a favourable environment to trigger the tumor-causing cascade of molecular events.

 

Incidentally, this is not the first time that bacteria have been shown to be at the root of colon cancer. Earlier in December 2017, a study published in Science provided details on a bacterium that was found predominantly in colorectal tumors. Fusobacterium nucleatum were found to be prevalent in local and metastatic sites of colorectal cancer. Along with F. nucleatum, researchers found a community of bacteria that were identical and co-existed together at each tumorigenic site. So, it appears these bacteria travel with cancer cells to their metastatic destinations. So far, the exact method by which Fusobacteria cause tumorigenesis is not clear.

 

The science of tumorigenesis is important to understand how to tackle the disease. And so, with this fundamental discovery, there are new possibilities of treating colon cancer patients beginning at the diagnostic stage. In the era of personalized medicine, the discovery of tumorigenic bacteria helps diagnosis. Patients going through colonoscopy can be tested for the causative types of bacteria. And in the event, these patients test positive, personalized treatments, such as vaccinations or specific narrow-spectrum antibacterial drugs will be effective.

 

Currently, antibiotics are broad-spectrum and may actually do more harm than good by eliminating beneficial bacteria along with the tumor-causing ones. In this regard, a significant discovery was made in the first week of February 2018. Scientists appear to have devised a way of turning off the antibiotic resistance gene of cancer cells. By using near infrared laser treatment and drug-carrying nanoparticles, the efflux pumps that expel drugs and other toxins from cells, are turned off. During this period, cancer cells can be specifically targeted with chemotherapy drugs without the fear of cells becoming resistant to the drugs. This research is still in its infancy but it provides hope and optimism that treatments involving specific targeting of cancer cells where normal cells are spared, maybe just around the corner.

 

Perhaps in the future, there may be potential for identifying the precise bacteria causing tumorigenesis. With this exact diagnosis, a suitable treatment strategy may be devised where the precise antibiotic to target the bacteria may be utilized. In order that the drugs do not target healthy cells, markers on cancer cells that could cause drug resistance may be downregulated or silenced for a short period till the drugs achieve their target of eliminating the cancer cells. The patient is spared of losing their healthy cells and the tumor is eliminated with minimum damage to the body’s system.

 

Bacteria in our bodies can be a boon when they are in harmony and in the right balance. Tilting the balance can have adverse outcomes as observed in the latest research on colon cancer. The gut microbiome certainly deserves our respect. So, let us be kind to our gut as these microbes can pack a punch!

BY Smitha Dutt