Antibiotics, microbiome and bowel cancer

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“Over the past thirty years, I have noticed an increase in the number of young, fit people, who do not have the associated risk factors, be diagnosed with bowel cancer,” says Dr Leslie Samuel, Consultant Oncologist at NHS Grampian.

This got me thinking about whether antibiotic use might be a contributing factor to these cases, since so many of us are exposed to antibiotics these days..”

Nearly 120 people will be diagnosed with bowel cancer, cancer that starts in the large intestine (colon) and rectum, every day in the UK. Of these cases, 54% are identified as “preventable” cancers.

Factors associated with an increased risk of bowel cancer include eating processed meats, being overweight or obese, smoking, and drinking alcohol.

Bowel cancer is also more common in older people. However, in recent decades, scholars like Samuel started noticing this unusual pattern.

Since the 1990s, the rate of bowel cancer has more than doubled in adults under 50 in America. OIn the United Kingdom, bowel cancer incidence rates increased by 50% among those under 50. This fell from an average of 4.5 per 100,000 people between 1993 and 1995 to an average of 6.7 per 100,000 people between 2016 and 2018.

Samuel, working alongside Sarah Perrott from the University of Aberdeen, set out to investigate the rising tide of early-onset bowel cancer and the potential role antibiotics could play.

They recently published the results of their study in the British Journal of Cancerwho found that the use of antibiotics can increase the risk of developing bowel cancer in the colon.

Another piece of the puzzle

The team, funded by us, analyzed data from 7,903 people with bowel cancer and compared them to more than 30,000 matched people without a diagnosis of cancer.

Although research has suggested there is no link between antibiotics and rectal cancer, the study found that antibiotic use was associated with 445 cases of bowel cancer in less 50 years old. While it’s important to remember that these numbers are still relatively low, these results may have pointed us to another piece of the puzzle.

“We found that antibiotic exposure was associated with colon cancer in all age groups, but not with rectal cancer,” Perrott says. “This, along with multiple other diet and lifestyle factors, may contribute to the rise in bowel cancer cases among young people.”

Additionally, the team then analyzed data from a small subset of those who had developed early bowel cancer and found that cancer that developed in the right side of the bowel was more strongly associated with the use of antibiotics than the left hand. side.

“The right side of the gut has a greater diversity of bacteria,” Perrott says. “So it all makes sense when you think about gut contents, gut microbiota activity and the theory of bowel cancer development”.

“Think of a Meadow”

People say there are more stars in the universe than grains of sand on earth, more sheep than people in New Zealand, and more bacteria in our bodies than human cells.

Many of these bacteria live in our gut.

This vibrant community, known as the microbiome, can help protect us from harm while delivering nutrients to our cells. But certain bacteria have been linked to a host of different diseases, from diabetes and mental health to cancer.

The link between the intestinal microbiota and bowel cancer (also known as colorectal cancer) has been researched for a while now and the theory behind these latest results is that the gut microbiome is impacted when you take antibiotics, a process known as dysbiosis.

If you think of a meadow with lots of different grasses and wildflowers, if we were to then spread weedkiller, it would kill specific species, but not all of them,” says Perrott.

This would then disturb the natural biodiversity of the grassland. As a result, for example, more weeds can grow because there is less competition. We don’t like weedsthey could block the sun for other wildflowers, they could change the pH of the soil and continue to disturb the prairie.

Perrott explains that a similar situation occurs with antibiotics – they can selectively kill certain types of bacteria living in the gut. This can lead to other strains of bacteria becoming dominant and disrupting the natural balance of our gut, which helps keep our gut healthy and contributes to normal immune function. In theory, it is this imbalance that could lead to chronic inflammation and increase the risk of cancer.

Although this is a potential mechanism, we have only just begun to untangle the complex ecosystem that exists inside our gut. We still have a lot to understand about which antibiotics might increase the risk.

“Antibiotic exposure is very common, and of course not everyone exposed to antibiotics develops bowel cancer,” adds Perrott. “We want to emphasize that antibiotics are very, very important medicines, but they should be used with care and when use is necessary.

What else do we know so far?

Samuel and Perrott aren’t the first to explore this relationship.

A few years ago, Dr. Cindy Sears, based on the East Coast of America, published an article in the journal Intestine, who saw a trend similar to that reported by Samuel and Perrott.

I think it’s impressive that primary research studies have been largely consistent, not necessarily in fine detail, but in the general concept that exposure to antibiotics, remote diagnosis of bowel cancer, is associated with disease,” says Sears.

Sears’ 2019 paper used data from more than two decades, allowing us to see over a much longer time frame how antibiotics might affect cancer risk.

Interestingly, the association with antibiotics “was only seen when the antibiotics were taken 10 years before the onset of the cancer,” says Sears. “And the reason it’s an attractive number, which has just come out of the data, is because it’s the magic number that people are talking about, in terms of the time between a cell deteriorating in the epithelium of the colon and the ability of gastrointestinal doctors to see intestinal tumors at colonoscopy”.

Now, this particular article by Samuel and Perrott is what many of us wondered given the explosion in antibiotic use in the 1980s to 1990s..”

Samuel and Perrott’s work adds to a plethora of existing research.

The nuances of these results become important because they add to the drumbeat of why antibiotic use should be done right. Antibiotics save lives. But the problem we had was that we got very lax.

Dr Cindy Sear

Problems of antibiotic overuse are widespread – antibiotic resistance being one of the most discussed and pressing issues. And while these data bolster the argument that antibiotic use should be reserved for situations where there is a real need, Perrott and Sears are quick to point out how important antibiotics are.

“Ultimately, this research is really part of a larger conversation about the gut microbiome and gut health,” says Samuel.

The bigger picture

There is still so much to learn about the microbiome, but we are making real progress.

By Cancer Grand Challengeswe support an international group of scientists studying how the microbiome drives bowel cancer and whether we can manipulate it to find new avenues for prevention and treatment.

Although this program does not study the link between antibiotics and bowel cancer, it does explore other important aspects of the microbiome, including looking for patterns associated with cancer development that may be linked to an increase in cancer of early onset bowel. Sears is part of the team taking on the microbiome challenge, bringing its expertise in infectious diseases.

As the global research community increasingly focuses on the microbiome, we now have a series of studies looking at its association with bowel cancer, and people are asking the questions in different populations,” Sears says.

“The next key step is to figure out how we can convert everything we’ve learned into prevention.”

Lily

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