Nav: Home

Gut microbiota imbalance promotes the onset of colorectal cancer

November 18, 2019

The gastroenterology team at Henri-Mondor AP-HP Hospital and University Paris-Est Créteil, led by Professor Iradj Sobhani, together with teams from Inserm and the Institut Pasteur Molecular Microbial Pathogenesis Unit (U1202), led by Professor Philippe Sansonetti - holder of the Microbiology and Infectious Diseases Chair at the Collège de France -, have demonstrated that an imbalance in the gut microbiota, also known as "dysbiosis", promotes the onset of colorectal cancer. The teams, operating as the "Oncomix" group since April 2016, demonstrated that transplanting fecal flora from patients with colon cancer into mice caused lesions and epigenetic changes characteristic of the development of a malignant tumor.

The pilot study, funded by the French National Cancer Institute and promoted by the Paris Public Hospital Network (AP-HP) as part of a hospital program for clinical cancer research (PHRC-K), led to the development of a non-invasive blood test which identifies the epigenetic phenomenon associated with dysbiosis. The test was validated in 1,000 individuals. These findings were published in the journal Proceedings of the National Academy of Sciences (PNAS) on November 11, 2019.

Sporadic colorectal cancer can develop in patients without any known risk factors. It occurs as a result of complex interactions between individuals and their environment. The increasing incidence of this condition reflects negative environmental developments, which can trigger alterations to the genetic and epigenetic DNA of host cells, thereby promoting the onset of sporadic colorectal cancer.

Several studies have investigated the role of the microbiota as a mediator of these interactions. The team in the Gastroenterology Department at Henri-Mondor AP-HP Hospital and University Paris-Est Créteil, together with a team composed of members from Inserm and the Institut Pasteur Molecular Microbial Pathogenesis Unit (U1202), and the Chair in Microbiology and Infectious Diseases at the Collège de France, demonstrated in mice that the epigenetic mechanism triggered by some bacteria in the microbiota contributes to the onset or promotion of sporadic colorectal cancer. They subsequently validated their findings in humans.

The 136 mice in the study were transplanted with either fresh stools from nine patients with sporadic colorectal cancer or fresh stools from nine patients with no colon disorders. The procedure was carried out at Henri-Mondor AP-HP Hospital. The colons of the mice were examined 7 and 14 weeks after the human fecal microbiota transplant. The teams particularly investigated the number and development of aberrant crypt foci (or ACF, a type of precancerous lesion), the microbial profile and damage to colonic DNA. They also took into account the animals' food intake, weight and blood indicators.

A link between fecal dysbiosis (an imbalance in gut bacteria composition) and the genetic and epigenetic DNA signature in the animals' tissues was identified using statistical tests. Mice who had received fresh stools from patients with sporadic colorectal cancer developed precancerous lesions known as aberrant crypt foci (ACF) without any significant genetic changes to the colon, but they had a greater number of hypermethylated genes - which have been significantly linked to the incidence of ACF in the colonic mucosa.

After verifying links between fecal dysbiosis and DNA anomalies (methylation) in the patients with sporadic colorectal cancer who took part in the fecal transplants, a pilot study was carried out in humans with the aim of developing a simple, reproducible blood test that can be used for early-stage diagnosis of colorectal tumors in asymptomatic patients. Prospective validation of the test was performed on 1,000 asymptomatic patients who were due to be given a colonoscopy. To identify the bacteria involved, their entire bacterial genome was sequenced. The level of hypermethylation of three genes was defined as a cumulative methylation index (CMI). The patients were classified according to their CMI (positive or negative). An analysis identified a positive CMI as a predictive factor for the onset of sporadic colorectal cancer.

This research shows that the microbiota of subjects with sporadic colorectal cancer induces precancerous colonic lesions in animals by the hypermethylation of a small number of genes. The CMI and/or methylating bacteria could therefore be used as diagnostic markers for this type of cancer. These initial findings will need to be evaluated and confirmed in a clinical trial.

Institut Pasteur

Related Cancer Articles:

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at