Scientists have discovered more than 140 medications that alter the gut microbiome, forcing bacteria to compete for nutrients, a phenomenon known to cause an intestinal imbalance and prompt cancer-promoting inflammation.
Stanford University researchers focused on common medications that impact the vast array of microbes in the gut, with potentially far-reaching consequences for metabolism, immune system response and overall health.
They found that potentially deadly changes in the gut result from certain medications killing off populations of bacteria and changing the availability of nutrients.
The impactful drugs included 51 antibiotics, certain chemotherapy medicines, antifungal medications and antipsychotics used to treat bipolar disorder and schizophrenia.
The drugs created a new environment in the gut in which the most drug-resistant bacteria survived and weaker strains were killed off.
When drugs kill weaker populations of gut bacteria, however, all the sugars, amino acids and other molecules they were sustained on are left in the gut for the more dangerous strains to thrive on.
This allows harmful, inflammatory species to explode in growth, which can permanently alter the gut balance, creating a state that promotes cancer.
The surviving bacteria are able to reshape the body’s microbiome, the collection of healthy bacteria that boosts the immune system and fights viruses, into a pro-inflammatory state, raising the risk of colorectal cancer.
Lead researcher Dr Handuo Shi said in a statement: ‘In other words, drugs don’t just kill bacteria; they also reshuffle the “buffet” in our gut, and that reshuffling shapes which bacteria win.’
Dr KC Huang, a microbiologist and immunologist at Stanford, and lead researcher, added: ‘Understanding how microbes are competing for food ends up telling a really large part of this collateral damage story.
‘It enables us to predict who is going to live, who is going to die, and makes the ensuing chaos seem really intuitive. I think that’s what we’re most excited about.’
The research team took a human fecal sample, used it to colonize a mouse, and then used its gut contents to create a stable microbial community that they could grow in a lab dish.
The bacterial community in their guts contained dozens of different species interacting as they would in a human gut.
Then, they exposed the mice to 707 different drugs, one per experiment, all at the same concentration.
After growing over a dozen communities of bacteria with the drugs, they tested how many of those communities of bacteria survived after being introduced to the medications, the nutrients and waste products left behind from dying strains and measured the overall growth of the community as a whole to see how much each drug inhibited it.
A key example researchers found pertained to two beneficial bacterial species, which survived in a test tube when exposed to the antifungal drug bifonazole. The bacteria rely on an iron-containing molecule called heme for food, which scientists added.
In the gut, these same bacteria do not get their heme directly and must rely on other bacteria to produce and supply it. The antifungal drug, however, killed the bacteria that usually provide this crucial compound, cutting off the species’ food supply.
Suddenly starved and weakened, the beneficial bacterial species became vulnerable to a drug they could previously resist, allowing harmful strains of bacteria to take up the leftover nutrients and flourish.
The damage caused by the 141 drugs that wiped out entire communities of bacteria was often permanent, with communities failing to return to their original states after the drugs were removed.
The resulting imbalance creates a state of chronic inflammation in the gut, which can damage colon cell DNA and fuel processes that lead to colorectal cancer.
An imbalanced microbiome also disrupts the mucosal barrier lining the intestines, allowing toxins and other harmful substances to leak into the intestinal tissue, which further fuels constant low-grade inflammation and spurs the development and clumping of cancer cells into tumors.
An imbalance, also known as dysbiosis, can produce harmful waste and byproducts known to promote cancer, including colibactin produced by certain E. coli bacteria.
Colibactin damages the DNA of colon cells, leading to mutations that influence the development of cancer.
Doctors across the US have been sounding the alarm for years about a rising number of bacterial strains that have become resistant to common antibiotics, requiring high doses of less commonly used drugs.
These drug-resistant infections have since been dubbed ‘superbugs.’
The American Cancer Society’s most recent investigation revealed a dramatic surge in colorectal cancer among adults under 55, with diagnoses in 45- to 49-year-olds accelerating from a one percent annual increase before 2019 to a 12 percent yearly rise through 2022.
A separate analysis posited that colon cancer is among the fastest-growing cancers in young adults, particularly 20 to 29-year-olds, where cases are surging by 2.4 percent per year on average.
The disease has already been projected to become the most common cancer in people under 50 by the year 2030.
The Stanford team’s work gives other scientists a tool to predict a drug’s impact on gut bacteria, opening the door to strategies that protect or rapidly rebuild a healthy microbiome after treatment.
Shi said: ‘Our study pushes a shift from thinking of drugs as acting on a single microbe to thinking of them as acting on an ecosystem.
‘If we can understand and model the ecosystem response, we could one day choose drugs and accompanying diets or probiotics not only based on how well they treat a disease, but also on how they preserve or promote a healthy microbiome.’
Their findings were published in the journal Cell.
