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Does This Bacterial Toxin Drive Early CRC Risk?
Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.
According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year.
A Potential Bacterial Connection
What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.
In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation.
These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure.
In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
Bacteria’s Cancer-Causing Properties
The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk.
Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
Colibactin and DNA Damage
Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.
In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions.
The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”
Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause.
Biofilms and Inflammation
Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.
Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.”
Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
Dysbiosis and Diet
Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.
In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment.
Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.
Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads.
Two Types of Bacterial Drivers
There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness.
These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”
E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor.
Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies.
E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.
Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
E coli and Inflammatory Bowel Disease
E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”
Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
Future Directions
Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention.
From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.
In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage.
A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.
Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.
A version of this article first appeared on Medscape.com.
Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.
According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year.
A Potential Bacterial Connection
What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.
In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation.
These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure.
In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
Bacteria’s Cancer-Causing Properties
The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk.
Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
Colibactin and DNA Damage
Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.
In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions.
The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”
Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause.
Biofilms and Inflammation
Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.
Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.”
Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
Dysbiosis and Diet
Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.
In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment.
Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.
Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads.
Two Types of Bacterial Drivers
There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness.
These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”
E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor.
Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies.
E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.
Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
E coli and Inflammatory Bowel Disease
E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”
Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
Future Directions
Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention.
From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.
In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage.
A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.
Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.
A version of this article first appeared on Medscape.com.
Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.
According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year.
A Potential Bacterial Connection
What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.
In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation.
These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure.
In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
Bacteria’s Cancer-Causing Properties
The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk.
Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
Colibactin and DNA Damage
Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.
In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions.
The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”
Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause.
Biofilms and Inflammation
Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.
Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.”
Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
Dysbiosis and Diet
Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.
In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment.
Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.
Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads.
Two Types of Bacterial Drivers
There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness.
These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”
E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor.
Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies.
E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.
Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
E coli and Inflammatory Bowel Disease
E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”
Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
Future Directions
Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention.
From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.
In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage.
A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.
Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.
A version of this article first appeared on Medscape.com.
Ten tips for boosting patient communication
This transcript has been edited for clarity.
Here are 10 ways to improve health communication with patients.
No. 1: Be an active listener
The first tip is to be an active listener and help guide the history-taking process by asking for clarification when needed.
Quickly figure out the patient’s chief complaint. Which symptom is the most severe?
Ask them for symptom-modifying factors, such as onset, duration, frequency, and a pain description. Is the abdominal pain sharp or crampy, dull and achy, or pressure-like? What makes the symptoms better or worse?
As many of us were taught in medical school, 80% of the diagnosis is in a patient’s history and description.
No. 2: Ask questions that resonate with patients
What can we do to help elicit an accurate history from the patient when they’re not providing the needed information or being helpful enough?
The easiest way is to ask your patient in a completely different way but one that resonates with them. For instance, ask how the abdominal pain is affecting their quality of life. That will help focus the history taking and encourage the patient to share details.
Does the pain keep them awake at night? Are they able to eat a normal-sized meal? Or are they forced to eat tiny snacks? Is the pain interfering with work or school?
By providing a framework, the patient will be more passionate about sharing the details of their history.
No. 3: Help patients organize their story
Sometimes, patients provide details in a nonchronological order, jumping all over the place.
A super helpful technique is to explain to the patient that you have a story to write for your computer note, and for them to think back to when they first started noticing their abdominal pain or rectal bleeding symptoms. When were the most-severe episodes? How frequent are the episodes? What’s the volume of their rectal bleeding?
If the patient realizes that you’re trying to write a story synopsis, they will provide information in a much more organized way.
No. 4: Determine patient’s language preference
Quickly determine the patient’s language preference. We want patients to feel extremely comfortable.
Whenever possible, use a certified interpreter. Language phone lines, in-person interpreters, and video conferencing are widely available today. It’s worth investing in this technology so that we can provide the best possible care to immigrants and refugees.
Conversely, avoid using family members as interpreters because they may not be adequately trained in medical vocabulary.
No. 5: Use simple language
When providing explanations, use simple language that your patient can understand and identify with.
For example, use analogies like “the heart is a pump” or the diverticula are thin areas of the colon that can bleed if the blood vessel is too close to the surface.
No. 6: Determine level of medical literacy
Determine your patient’s level of medical literacy. Some of our patients did not graduate from high school. Some patients can’t read very well. Therefore, your discharge instructions and handouts should sometimes be written on a third-grade level.
If patients can’t read, write medication instructions with symbols. Draw a sun for medications that are supposed to be taken in the morning and draw a moon if a medication is supposed to be taken at night.
Always very carefully review the instructions with the patient.
No. 7: Check in with the patient
During the visit, frequently check in with the patient to make sure that they understand what you’re asking or what you’re trying to explain to them.
No. 8: Include family member as patient advocate
If the patient is accompanied by a family member, help them serve in the important role as a patient advocate.
If the family member wants to take notes, encourage them because that provides an awesome value.
Sometimes patients can forget clinic and hospital medical conversations, and that family member might be the key to improving your patient’s health.
No. 9: Follow-up with the patient
If your clinic has the capability, follow up with a patient the next day to make sure that they understood everything.
Check to make sure the patient was able to pick up all of the medications that you prescribed.
Check that laboratory tests are arranged or completed.
Check that important procedures, such as esophagogastroduodenoscopy and colonoscopy, and imaging, such as ultrasounds and CTs, are scheduled.
No. 10: Identify barriers to care
Have fun talking with a patient. Find out what they do for a living. Build a rapport. Listen to their stressors in life.
Try to identify any barriers to care or external stressors, like taking care of a sick parent, which might interfere with their scheduling an important diagnostic colonoscopy for rectal bleeding.
Good luck incorporating these communication strategies into your clinic and hospital work. Together, we can help improve the delivery of health care.
Dr. Levy is a gastroenterologist at the University of Chicago. In 2017, Dr. Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Dr. Levy, who recently gave a TEDx Talk about building health education campaigns using music and concerts, organizes Tune It Up: A Concert To Raise Colorectal Cancer Awareness with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee. He has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Here are 10 ways to improve health communication with patients.
No. 1: Be an active listener
The first tip is to be an active listener and help guide the history-taking process by asking for clarification when needed.
Quickly figure out the patient’s chief complaint. Which symptom is the most severe?
Ask them for symptom-modifying factors, such as onset, duration, frequency, and a pain description. Is the abdominal pain sharp or crampy, dull and achy, or pressure-like? What makes the symptoms better or worse?
As many of us were taught in medical school, 80% of the diagnosis is in a patient’s history and description.
No. 2: Ask questions that resonate with patients
What can we do to help elicit an accurate history from the patient when they’re not providing the needed information or being helpful enough?
The easiest way is to ask your patient in a completely different way but one that resonates with them. For instance, ask how the abdominal pain is affecting their quality of life. That will help focus the history taking and encourage the patient to share details.
Does the pain keep them awake at night? Are they able to eat a normal-sized meal? Or are they forced to eat tiny snacks? Is the pain interfering with work or school?
By providing a framework, the patient will be more passionate about sharing the details of their history.
No. 3: Help patients organize their story
Sometimes, patients provide details in a nonchronological order, jumping all over the place.
A super helpful technique is to explain to the patient that you have a story to write for your computer note, and for them to think back to when they first started noticing their abdominal pain or rectal bleeding symptoms. When were the most-severe episodes? How frequent are the episodes? What’s the volume of their rectal bleeding?
If the patient realizes that you’re trying to write a story synopsis, they will provide information in a much more organized way.
No. 4: Determine patient’s language preference
Quickly determine the patient’s language preference. We want patients to feel extremely comfortable.
Whenever possible, use a certified interpreter. Language phone lines, in-person interpreters, and video conferencing are widely available today. It’s worth investing in this technology so that we can provide the best possible care to immigrants and refugees.
Conversely, avoid using family members as interpreters because they may not be adequately trained in medical vocabulary.
No. 5: Use simple language
When providing explanations, use simple language that your patient can understand and identify with.
For example, use analogies like “the heart is a pump” or the diverticula are thin areas of the colon that can bleed if the blood vessel is too close to the surface.
No. 6: Determine level of medical literacy
Determine your patient’s level of medical literacy. Some of our patients did not graduate from high school. Some patients can’t read very well. Therefore, your discharge instructions and handouts should sometimes be written on a third-grade level.
If patients can’t read, write medication instructions with symbols. Draw a sun for medications that are supposed to be taken in the morning and draw a moon if a medication is supposed to be taken at night.
Always very carefully review the instructions with the patient.
No. 7: Check in with the patient
During the visit, frequently check in with the patient to make sure that they understand what you’re asking or what you’re trying to explain to them.
No. 8: Include family member as patient advocate
If the patient is accompanied by a family member, help them serve in the important role as a patient advocate.
If the family member wants to take notes, encourage them because that provides an awesome value.
Sometimes patients can forget clinic and hospital medical conversations, and that family member might be the key to improving your patient’s health.
No. 9: Follow-up with the patient
If your clinic has the capability, follow up with a patient the next day to make sure that they understood everything.
Check to make sure the patient was able to pick up all of the medications that you prescribed.
Check that laboratory tests are arranged or completed.
Check that important procedures, such as esophagogastroduodenoscopy and colonoscopy, and imaging, such as ultrasounds and CTs, are scheduled.
No. 10: Identify barriers to care
Have fun talking with a patient. Find out what they do for a living. Build a rapport. Listen to their stressors in life.
Try to identify any barriers to care or external stressors, like taking care of a sick parent, which might interfere with their scheduling an important diagnostic colonoscopy for rectal bleeding.
Good luck incorporating these communication strategies into your clinic and hospital work. Together, we can help improve the delivery of health care.
Dr. Levy is a gastroenterologist at the University of Chicago. In 2017, Dr. Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Dr. Levy, who recently gave a TEDx Talk about building health education campaigns using music and concerts, organizes Tune It Up: A Concert To Raise Colorectal Cancer Awareness with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee. He has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Here are 10 ways to improve health communication with patients.
No. 1: Be an active listener
The first tip is to be an active listener and help guide the history-taking process by asking for clarification when needed.
Quickly figure out the patient’s chief complaint. Which symptom is the most severe?
Ask them for symptom-modifying factors, such as onset, duration, frequency, and a pain description. Is the abdominal pain sharp or crampy, dull and achy, or pressure-like? What makes the symptoms better or worse?
As many of us were taught in medical school, 80% of the diagnosis is in a patient’s history and description.
No. 2: Ask questions that resonate with patients
What can we do to help elicit an accurate history from the patient when they’re not providing the needed information or being helpful enough?
The easiest way is to ask your patient in a completely different way but one that resonates with them. For instance, ask how the abdominal pain is affecting their quality of life. That will help focus the history taking and encourage the patient to share details.
Does the pain keep them awake at night? Are they able to eat a normal-sized meal? Or are they forced to eat tiny snacks? Is the pain interfering with work or school?
By providing a framework, the patient will be more passionate about sharing the details of their history.
No. 3: Help patients organize their story
Sometimes, patients provide details in a nonchronological order, jumping all over the place.
A super helpful technique is to explain to the patient that you have a story to write for your computer note, and for them to think back to when they first started noticing their abdominal pain or rectal bleeding symptoms. When were the most-severe episodes? How frequent are the episodes? What’s the volume of their rectal bleeding?
If the patient realizes that you’re trying to write a story synopsis, they will provide information in a much more organized way.
No. 4: Determine patient’s language preference
Quickly determine the patient’s language preference. We want patients to feel extremely comfortable.
Whenever possible, use a certified interpreter. Language phone lines, in-person interpreters, and video conferencing are widely available today. It’s worth investing in this technology so that we can provide the best possible care to immigrants and refugees.
Conversely, avoid using family members as interpreters because they may not be adequately trained in medical vocabulary.
No. 5: Use simple language
When providing explanations, use simple language that your patient can understand and identify with.
For example, use analogies like “the heart is a pump” or the diverticula are thin areas of the colon that can bleed if the blood vessel is too close to the surface.
No. 6: Determine level of medical literacy
Determine your patient’s level of medical literacy. Some of our patients did not graduate from high school. Some patients can’t read very well. Therefore, your discharge instructions and handouts should sometimes be written on a third-grade level.
If patients can’t read, write medication instructions with symbols. Draw a sun for medications that are supposed to be taken in the morning and draw a moon if a medication is supposed to be taken at night.
Always very carefully review the instructions with the patient.
No. 7: Check in with the patient
During the visit, frequently check in with the patient to make sure that they understand what you’re asking or what you’re trying to explain to them.
No. 8: Include family member as patient advocate
If the patient is accompanied by a family member, help them serve in the important role as a patient advocate.
If the family member wants to take notes, encourage them because that provides an awesome value.
Sometimes patients can forget clinic and hospital medical conversations, and that family member might be the key to improving your patient’s health.
No. 9: Follow-up with the patient
If your clinic has the capability, follow up with a patient the next day to make sure that they understood everything.
Check to make sure the patient was able to pick up all of the medications that you prescribed.
Check that laboratory tests are arranged or completed.
Check that important procedures, such as esophagogastroduodenoscopy and colonoscopy, and imaging, such as ultrasounds and CTs, are scheduled.
No. 10: Identify barriers to care
Have fun talking with a patient. Find out what they do for a living. Build a rapport. Listen to their stressors in life.
Try to identify any barriers to care or external stressors, like taking care of a sick parent, which might interfere with their scheduling an important diagnostic colonoscopy for rectal bleeding.
Good luck incorporating these communication strategies into your clinic and hospital work. Together, we can help improve the delivery of health care.
Dr. Levy is a gastroenterologist at the University of Chicago. In 2017, Dr. Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Dr. Levy, who recently gave a TEDx Talk about building health education campaigns using music and concerts, organizes Tune It Up: A Concert To Raise Colorectal Cancer Awareness with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee. He has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.