Gut reaction: Taking oral antibiotics contributes to antibiotic resistance

COLUMBUS — As concern about antibiotic-resistant organisms grows, an Ohio State University researcher has identified a potentially critical cause for their proliferation: the widespread use of oral antibiotics.

Taking antibiotics orally exposes the microflora in the digestive system to those medicines, and this exposure in itself could be a significant cause of the increase in antibiotic-resistant bacteria seen, according to a new study by Hua Wang, associate professor of food science and technology with the College of Food, Agricultural, and Environmental Sciences, and postdoctoral research associate Lu Zhang.

“We have known for a long time that use of antibiotics leads to antibiotic resistance, and many have called for reducing the use of antibiotics, in both human medicine and in agriculture, as a solution,” Wang said.

Now, her research offers another possible answer.

Transferring resistance

In previous work, Wang and her team identified large quantities of pervasive antibiotic-resistant genes in commensal (harmless or even beneficial) bacteria in conventional foods, and realized it would be relatively easy for these bacteria to transfer their drug-resistant properties to pathogenic (disease-causing) bacteria.

Then the researchers found resistant bacteria rapidly developed in human infants’ gut microflora that had not yet been exposed to antibiotics, suggesting the involvement of other risk factors.

Taken together, these findings triggered a new hypothesis, Wang said.

What’s changed?

“Before the 1980s, a drug could last (without most pathogens developing resistance to it) for 30 or 40 years,” Wang said. “Why did penicillin last so long? Why do pathogens develop resistance to new drugs so quickly now?

“Is it only because we overuse them, or that we’ve been using them in food-producing animals? Or is it possible that it’s also related to how we have changed our ways of giving antibiotics?”

Delivery method suspect

It’s been only in recent decades that antibiotics have been prescribed primarily as pills to be taken orally rather than given as injections, Wang said.

In addition, antibiotics are often mixed in livestock feed or water, thus entering animals’ digestive systems as well.

Antibiotic-resistant bacteria and resistance gene pools, which can further spread resistance, significantly increase when antibiotic residues and bacteria encounter each other in the digestive system.

Through human and animal waste, those gene pools, as well as the resistant bacteria, become even more pervasive throughout the environment, and affect humans again through food chain and environmental contact, Wang said.

Her research

To test the theory that oral administration of antibiotics could make a difference in antibiotic resistance, Wang and Zhang studied colonies of lab mice, some of which were inoculated with antibiotic-resistant Enterococcus or Escherichia coli. The mice were then given an antibiotic — either tetracycline hydrochloride or ampicillin — at different dosage levels in either their feed or by injection.

The researchers found that antibiotic-resistant bacteria developed sooner or were up to 100 times higher in mice given antibiotics orally compared with mice given the same dosage by injection.

In a group of mice that were not exposed to drug-resistant bacteria, neither the oral nor injected antibiotics caused antibiotic-resistant genes to develop in the gut microflora during the study, Wang said.

It’s all in the gut

“This tells us that if there are no antibiotic-resistant organisms in the gut in the first place, the development of antibiotic resistance won’t occur very fast,” Wang said.

The findings make perfect sense, she said.

“If you take an oral drug, only a certain percentage of the drug will be absorbed into the bloodstream, but all of the gut microflora will be unnecessarily exposed to it.” Wang said. “With the injection, all of the dosage will first go into the bloodstream, and the gut microflora is not directly exposed to the drug.

“The basic dosage is more effective against infection, and the gut microflora will have much less exposure to antibiotics, thus providing less chance to develop resistance.”

Could impact future

Wang hopes this and future research will help public health authorities develop more targeted and effective guidelines for the use of antibiotics and will encourage drug manufacturers to develop new methods of administering antibiotics to slow the proliferation of antibiotic-resistant bacteria.

“Knowing where the problem came from is the first but critical step,” she said. “We can then look for targeted methods to control the problem. It is especially exciting when practical solutions may be available.”