Long-term antibiotic use linked to heightened risk of colorectal adenomas

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Long-term antibiotic use linked to heightened risk of colorectal adenomas Key period may be early to mid-life, findings suggest

Caroline White

Wednesday, 05 April 2017

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Long-term antibiotic use in early to mid-life may increase the risk of polyps or colorectal adenomas which precede the development of most cases of bowel cancer, reveals research* published online in the journal Gut.

The findings add to emerging evidence that the type and diversity of bacteria in the gut (the microbiome) may have a key role in the development of cancer, say the researchers.

Previous research has indicated that antibiotic use may be associated with a heightened risk of developing colorectal cancer, but these studies have involved relatively short monitoring periods, so undermining the strength of the associations found. And the potential association with polyp risk hasn’t been explored.

To try and get round these issues, the research team drew on data from the Nurses Health Study. This has been monitoring the health of 121,700 US nurses who were all aged between 30 and 55 when they entered the study in 1976.

Since joining, study participants have filled in detailed questionnaires every two years on demographics, lifestyle factors, medical history and disease development, and every four years on their dietary habits.

For the purposes of the current study, analysis of the data was restricted to 16,642 women who were aged 60 and older in 2004, who were able to provide a history of antibiotic use between the ages of 20 and 59, and who had had at least one colonoscopy between 2004 and 2010.

During this period, 1,195 adenomas were newly diagnosed in these women.

Recent use of antibiotics within the past four years wasn’t associated with a heightened risk of an adenoma diagnosis, but long-term use in the past, was.

Compared with those who hadn’t taken antibiotics for any extended period in their 20s and 30s, those who had taken them for two months or more were 36% more likely to be diagnosed with an adenoma.

This association held true irrespective of whether the adenoma was considered high or low risk for bowel cancer, but was stronger for growths located in the proximal, rather than the distal, colon.

Similarly, women who had taken antibiotics for two months or more during their 40s and 50s were 69% more likely to be diagnosed with an adenoma than those who hadn’t taken these drugs for any extended period.

Once again, this association held true, irrespective of whether the adenoma was high or low risk for bowel cancer, and was more strongly linked to proximal colorectal adenomas.

And compared with women who had not been on antibiotics for any length of time from their 20s to their 50s, those who had taken these drugs for more than 15 days between the ages of 20 and 39, and between the ages of 40 and 59, were 73% more likely to be diagnosed with an adenoma.

This is an observational study so no firm conclusions can be drawn about cause and effect, added to which no information was obtained on the type or formulation of antibiotic taken, and some adenomas might have been present before antibiotics were used, the researchers point out.

Nevertheless, there is a plausible biological explanation for the associations found, they suggest.

Antibiotics fundamentally alter the gut microbiome, by curbing the diversity and number of bacteria, and reducing resistance to ‘hostile’ bugs, they say. Previous research points to depletion of certain types of bacteria and an abundance of others in patients with bowel cancer.

“The findings, if confirmed by other studies, suggest the potential need to limit the use of antibiotics and sources of inflammation that may drive tumour formation,” conclude the researchers.

However, Dr Sheena Cruickshank, British Society for Immunology spokesperson, and Senior Lecturer in Immunology, University of Manchester, sounded a note of caution.

“Whilst the data adds to our growing knowledge of the importance of the gut bacteria to our health, I would be concerned about advising people to avoid using antibiotics. Antibiotics are crucial medicines for treating bacterial infections and, if prescribed and used appropriately, can be life-saving,” she said.

* Cao Y, Wu K, Mehta R, et al. Long-term use of antibiotics and risk of colorectal adenoma. Gut, published online first: 04 April 2017. DOI: 10.1136/gutjnl-2016-313413

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