A new study suggests that Clostridioides difficile is responsible for certain colorectal cancers.
According to data gathered by scientists at the Bloomberg Kimmel Institute for Cancer Immunotherapy and the Johns Hopkins Kimmel Cancer Center, the bacterial species Clostridioides difficile, or C. diff, which is well known for causing serious diarrheal infections, may also cause colorectal cancer.
The research, which was recently published in the journal Cancer Discovery, may reveal another problematic role for this microbe, which causes over 500,000 infections annually in the United States, many of which are very challenging to treat.
“The uptick of individuals under age 50 being diagnosed with colorectal cancer in recent years has been shocking. We found that this bacterium appears to be a very unexpected contributor to colon malignancy, the process by which normal cells become cancer,” says Cynthia Sears, M.D., Bloomberg~Kimmel Professor of Cancer Immunotherapy and professor of medicine at the Johns Hopkins University School of Medicine.
Researchers in the Sears Lab reported several years ago that more than half of colorectal cancer patients had bacterial biofilms — dense colonies of bacteria on the colon surface — while only 10% to 15% of healthy people without tumors had biofilms. However, one sample stood out to the researchers when they infected mice with biofilm samples originating from specific colorectal cancer patients because it significantly raised colorectal tumors in the mice. This slurry caused tumors in 85% of the mice, while in most controls, tumor development is less than 5%.
In additional work, the team identified a patient sample without a biofilm that similarly increased colorectal tumors in the mice. Although several bacterial species have been linked with colorectal cancer — including enterotoxigenic Bacteroides fragilis, Fusobacterium nucleatum, and a specific strain of Escherichia coli — these microbes were either absent in the tumors of these two patients (B. fragilis and E. coli) or did not successfully colonize the mice (F. nucleatum), suggesting that other bacteria were responsible for promoting the colorectal cancer cascade.
To determine which bacteria may be causing tumors in the mice, Sears, along with study co-authors Julia Drewes, Ph.D., assistant professor of medicine, Jie (Angela) Chen, Ph.D., Jada Domingue, Ph.D., of Johns Hopkins, and colleagues performed additional experiments to see if a single bacterial species or a community of bacteria were promoting tumor formation in the mice.
They noted that toxigenic C. difficile, the type of C. difficile that causes diarrhea, was absent in the samples that did not cause tumors, but was present in the samples that caused tumors in mice. When the researchers added this bacterium to the samples that originally did not cause tumors, it induced colon tumors in the mice. Further testing showed that C. difficile alone was sufficient to prompt tumor formation in the animal models.
Additional experiments led by co-author Nicholas Markham, M.D., Ph.D., assistant professor of medicine at Vanderbilt University Medical Center, and study co-leaders Franck Housseau, Ph.D., associate professor of oncology at Johns Hopkins, and Ken Lau, Ph.D., associate professor of cell and developmental biology and surgery at Vanderbilt University School of Medicine, showed that C. difficile brought about a range of changes within colon cells that made them vulnerable to cancer.
Cells exposed to this bacterium turned on genes that drive cancer and turned off genes that protect against cancer. These cells produced reactive oxygen species, unstable molecules that can damage DNA, and they also prompted immune activity associated with harmful inflammation.
A toxin produced by this bacterium — known as TcdB — appears to cause most of this activity, the researchers say. When they used genetically engineered C. difficile strains that contained inactivated toxin genes and/or released a related C. difficile toxin called TcdA, mice infected with the TcdB-inactivated microbes produced far fewer tumors than those with TcdB-active ones, while TcdA made by C. difficile was not sufficient to cause tumors.
To date, Drewes says, there is limited epidemiological data linking C. difficile with colorectal cancer in humans, but if further research shows that a connection exists, it could lead to screening for latent C. difficile infection or previous infection as a risk factor for cancer. Since lengthy exposures to TcdB may increase colorectal cancer risk, an important prevention effort could include heightened efforts to eradicate this pathogen quickly and effectively, which recurs — often repeatedly — in 15%–30% of infected patients after initial treatment, including in pediatric patients.
“While this link between C. difficile and colorectal cancer needs to be confirmed in prospective, longitudinal cohorts, developing better strategies and therapeutics to reduce the risk of C. difficile primary infection and recurrence could both spare patients the immediate consequences of severe diarrhea and potentially limit colorectal cancer risk later on,” Drewes says.
Reference: “Human Colon Cancer–Derived Clostridioides difficile Strains Drive Colonic Tumorigenesis in Mice” by Julia L. Drewes, Jie Chen, Nicholas O. Markham, Reece J. Knippel, Jada C. Domingue, Ada J. Tam, June L. Chan, Lana Kim, Madison McMann, Courtney Stevens, Christine M. Dejea, Sarah Tomkovich, John Michel, James R. White, Fuad Mohammad, Victoria L. Campodónico, Cody N. Heiser, Xinqun Wu, Shaoguang Wu, Hua Ding, Patricia Simner, Karen Carroll, Martha J. Shrubsole, Robert A. Anders, Seth T. Walk, Christian Jobin, Fengyi Wan, Robert J. Coffey, Franck Housseau, Ken S. Lau and Cynthia L. Sears, 7 June 2022, Cancer Discovery.
The study was funded by the National Institutes of Health, the Bloomberg~Kimmel Institute for Immunotherapy, Cancer Research UK, the Johns Hopkins University Department of Medicine, the Johns Hopkins Kimmel Cancer Center Core, and the Department of Veterans Affairs.
This could be useful! Colorectal cancer is out of control in the Lower Mainland of BC and no one knows why?
Sam, probably a coincidence. But if you’d feel safer move away from there to lower rates. Nobody knows what causes cancer only that in the cases in the study reflect that factor. So if you avoid this bacteria growth then you are less likely to develop colon cancer. If you already have factors then don’t move. Get a test to see which cancers are you inclined by a doctor. This will bring peace of mind.
I suspect many (most?) cancer starts as a bacterial or viral infection.
That might be true, but I suspect that bacterial/viral infections suppress the immune system to the point that a cancer start to bloom and take off because of it. Rather than the start, the bacteria/virus run screen and cancer goes in to score.
Nothing new here. Its just the first time said doctor discovered it. Viruses causing cancer for millennia.
Artificial sweetners interfere with gut biome. Propose the disruption allows C Diff to dominate other bacterium.
Which ones and in what quantity/dosage of intake?
I do know that artificial sweetners do horrible things to the body but i had never heard it causing C diff.
I have had 3 times now, 2 times i got it while hospitalized amd the 3 time from taking too many antibiotics(or so the dr said).
I recently started looking into artificial sweetners, i have never liked them but after i started reading ingredients i was stunned to see how many things contained sucralose. Even things i would have never thought of.
I am not shocked as i know many people use these artificial sweetners to avoid sugar and lose weight . Yet, they stay obese or even gain more weight.
I suspect that leukemia has a viral trigger too.
I pray that we can make a significant discovery in treatment of cancers!
68 years ago in med school at Iowa, prof Bill Fowler proposed that certain types of leukemia and lymphoma resulted from viral infection. It’s an idea that’s been around for a while. Alan Wentworth, MD
Is this really where we are on cancer research? Hundreds of billions of dollars spent on cancer research over the past few decades and we are just now getting to this? Very discouraging.
Can there be a link to probiotics and or prebiotics?
The cause of cancer is the thousands of harmful chemicals they are putting into our everyday needs!!!
Don’t forget one important piece of information: IN MICE, not in human patients. It is very tempting to transfer the findings, and it is indeed a starting point, but the immune systems and local environments (digestive systems) are so different that drawing a conclusion based on this data is very risky.
Raw garlic chewed produces immediate healing results,
So, if I had a bad case of C-Diff in 2008. Should I be concern? I have a pain in the lower left side for months now and they can’t find out why. I thought it was kidney issues.
I’m not so sure about this. It is something to ponder.
It’s like did the chicken or the egg come first.
Genetics play a significant role in determining which people are more susceptible to colon cancer. Because of this Genetic component, I believe this makes the person more prone to C-Diff.
I don’t think that C-Diff is the cause of colon cancer. We all have a small amount of C-Diff in our gut. Even babies.
It is when our gut is imbalances that the C-Diff grows and over produces. That imbalance could be due to cancer, antibiotics, autoimmune disorders, etc.
Just my opinion.
What if anything can we do to eliminate this bacteria
I have type 2 diabetes. Metformin was the first pill that was prescribed. The side effect of diarhea was explosive and after several of this pill ruling my life I said no more. Seeing this report I wonder if that diarrhea is the initial breeding ground for c. Diff.? I ask because I ended up with c. Diff. a couple of years later. My hospital was able to treat the C. Diff. successfully.
What data do you have? Are there diabetics? Have any been prescribed Metformin? Do they experience the explosive diarrhea? Have they also had c. Diff.
I am interested in hearing if my thoughts about this are worthwhile.
As more people make a living from cancer than die from it, this will be shut down very quickly
C diff is found in people with an already compromised immune system. It’s your immune system that fights off cancer everyday. You have had cancer many times without even knowing it,but your immune system took care of it. This study should not be surprising in the least.
Could anal sex cause the bacteria?
It will be discovered that some cancers are actually transmissible from host to host and infectious.
No one wants to cure cancer, this is all BS. My cancer gave $450,000 to big pharma, you think they want all that money to go away? If anybody cared insurance would cover ultrasounds, etc. It’s the only way.
In the case of rectal cancer with Lynch syndrome, (genetic), a small study was done with people who were on their way to chemo, radiation and surgery. A drug called “Dostarlimab” I believe eradicated the tumors completely. I think the participants were watched for two years and no signs of cancer returned. I read where they were going to see if this drug could be applied to other cancers. I believe this drug is also known by the name “Jemperli.” If you have rectal cancer have it biopsied and check for genetic inherited causes and talk to your doctors about this study.
What do you think is going to happen to non-profit organizations such as the American Cancer society if a cure for cancer is ever found?! I believe that the cure has already been found long ago, but of course money rules everything! Those non-profit organizations count on the money from people dying from cancer so once cancer is gone so is all their profits.
Too many females are led to believe by men that they have to sexually anal savy in order to please the man, which is just not true. All the serious infections like hiv/AIDS and now Monkey Pox are spread this way because please remember people, it’s the bottom of your intestines, not a sexual organ for Pete’s sake. Say “No”; Have some respect for yourselves
LOL. Your comment made me smile.
After having Crohns and UC for years and having all the problems i have endured in my intestines and the ‘bottom of the intestines’ in amy way ‘sexy’.
I am on the toilet 10- 15 times a day, i bleed everytime. I take alot of medication, and i am sick alot. I have been on hospice 2 times and blessed to say i survived and on palliative care now.
It’s been at the forefront of medical literature for decades that is you eat properly, exercise 30 minutes a day, don’t smoke, and don’t drink too much alcohol…all disease including cancer will go down by 40%…If everyone did that it would surely put big pharma under. But most people just don’t listen…that’s on them. Sad..To learn how to eat properly start with myplate.org
Doctor Technology Rene Delapaz ReyesGuevara HARVARD University UGB Delapaz ReyesGuevara HARVARD University UGB wcc b.t.c uw [email protected] wwu.edu 1942trigg rd Fernando wa98248 CIA 056f172501 CIA 85z6j87j 1000colonid Farm McLeanVA22101 CIA chesterfield County VA 23832-0297 ID WDLB5N18233B CIA 866-237-7221 1942trigg Rd Fernando wa98248 CIA 056f172501 CIA 85z6j87j 1000colonid Farm McLeanVA22101 CIA chesterfield County VA 23832-0297 wwu.edu
Since I have cancer how do I kill it . Without all the side effects from your chemo therapy . So get it figured out.
My case is an excellent example of this bacterial relationship to cancer. In 2015, I contracted the most severe form of C-diff resulting in hospitalization, 2 months bedrest, hair loss from malnutrition. etc.
EXACTLY 21/2 years later I was diagnosed with right ascending colon cancer, with distant perineal lymph node metastasis resulting in stage 4 diagnosis. Extensive surgery, chemo, and continuing health lifestyle while dealing with chronic gastrointestinal flare ups all have kept me “cancer free” since 2018. THERE IS NO DOUBT THAT A FOLLOW UP COLONOSCOPY POST CDIFF & REGULAR FOLLOW UPS SINCE MY CDIFF INFECTION WOULD HAVE CAUGHT THESE CHANGES & PREVENTED THIS DEADLY DIAGNOSIS
…IN ADDITION: I HAVE NO GENETIC PREDISPOSITION TOWARD COLON CANCER, ALSO TESTED (-) TO LYNCH SYNDROME, AND AS FAMILY GENEALOGY SHOWED NO HISTORY OF CANCER FOR PREVIOUS GENERATIONS. MY CDIFF RESULTED FROM TAKING A BROAD SPECTRUM ANTIBIOTIC FOR AN UPPER RESPIRATORY INFECTION .
I found this article very interesting. I have crohns and uc and have had c diff several times now. Each time i was so very sick. So it makes sense to me that it could somehow linked to cancer.
In 2017 was my first time getting it. I went into the hospital because of severe bleeding from IBD, my iron dropped to a 4. I needed blood transfusions and iron infusions. I was feeling better after i got out of ICU. I went home and within 5 or 6 days my rectal bleeding and pain was much worse. I went back to the hospital and had c diff. I was already weak and sick but this took the life out of me. It was many months until i felt better. Then another hospital stay and got it again.
Because it is so contagious, i wonder how many people who have been on the gastro floor in the hospital, how many end up with colorectal cancer. I would be interested in seeing some numbers on that.