How could antibiotics damage the gut and increase risk?

• As of 2019, about 4.9 million people globally were living with inflammatory bowel disease (IBD).
• There is currently no cure for IBD and scientists are still not sure what the exact cause of the condition is.
• Researchers from Bar-Ilan University have found via a mouse model that antibiotics may damage the protective mucus layer of the gut, potentially raising a person’s risk for IBD.

There is currently no cure for IBD and scientists are still not sure what the exact cause of the condition is.

Now researchers from Bar-Ilan University in Israel are helping to shed some light on a possible cause for IBD in a new study recently published in the journal ScienceAdvances that reports antibiotics may damage the protective mucus layer of the gut, potentially raising a person’s risk for IBD.

According to Shai Bel, PhD, principal investigator at the Azreili Faculty of Medicine at Bar-Ilan University in Israel and lead author of this study, the team decided to specifically examine antibiotic use and its potential impact on IBD risk because recent epidemiological studies have identified a strong link between antibiotic use and risk of developing IBD, in a dose-dependent manner.

“Unlike many other environmental factors, this is one that can be tested in the lab in a well-controlled fashion,” Bel told Medical News Today.

For this study, researchers used a mouse model of IBD with advanced techniques such as RNA sequencing, machine learning, and mucus secretion measurement to see how the antibiotics affected them.

At the study’s conclusion, Bel and his team found that antibiotics such as ampicillin, metronidazole, neomycin, and vancomycin damaged the protective mucus layer in the digestive tract, allowing bacteria to penetrate and potentially increasing gut inflammation risk.

“We always thought that antibiotics harm only bacteria and not us, but our new research has found that antibiotics directly affect the cells in our intestine,” Bel said. “This effect prevents our cells from secreting protective mucus, which can lead to penetration of bacteria into our tissues. In time, this persistence of bacteria where they are not supposed to be will trigger the body to activate an inflammatory response, which is the hallmark of IBD.”

Additionally, scientists found the negative impact of antibiotics on the intestine’s mucus barrier was not due to changes in the gut microbiome, but rather alterations directly to the intestinal wall cells responsible for mucus production.

“We were very surprised that antibiotics can affect mammals directly,” Bel added. “This is not common knowledge. Indeed, the vast use of antibiotics in medicine and agriculture is based on this assumption, which we discovered is wrong.”

“Antibiotics should absolutely be used when needed, but these days it is also over-prescribed,” he continued. “Perhaps with this new knowledge the use of antibiotics will be restricted to instances where it is proven it will be useful. The main takeaway is that antibiotics can affect us directly, independently of its effect on our bacteria. Next, we will test whether other predisposing factors are linked to antibiotic use in patients suffering from IBD.”

After reviewing this study, Harpreet Pall, MD, MBA, CPE, a pediatric gastroenterologist and chairman of Pediatrics at the K. Hovnanian Children’s Hospital at the Hackensack Meridian Jersey Shore University Medical Center in New Jersey, told MNT that this study provided him with important new insight as to how antibiotics might increase the risk of developing IBD.

“It is not necessarily the effect antibiotics have on the gut flora, but rather the direct effect they have on the protective layer on the inside of the gut,” Pall explained. “Antibiotics can disrupt this mucus layer, and this can cause bacteria to invade the gut wall leading to inflammation.”

“By better understanding the risk factors for IBD, researchers can work towards developing prevention strategies,” he continued.

“This approach can also lead to earlier detection and personalized treatment of IBD. I would love to see new potential treatment targets as a result of this research. Exploring how to decrease risk of IBD development in patients at high risk is an important area for further study,” Pall noted.

MNT also spoke with Ashkan Farhadi, MD, a board-certified gastroenterologist at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, about this study.

“The news of the study was a little bit shocking,” Farhadi commented. “It’s creating a seismic change in many things we’re thinking and we know about the mechanism of the disease and the way antibiotics work.“

“There were some reports that [the] use of antibiotics was associated with IBD. It was not quite known [whether] this was the effect of infection — that [the] personal gut and immune system got activated — or was the effect of antibiotics,” he explained.

“[Previously,] it was thought that even if [the] antibiotic is [the] culprit [in IBD], [the] antibiotic acts by modulating or reducing the bacteria in the gut, and that’s how it changes the microbiome environment in the gut, and it may cause some irritation or inflammation because of changing the balance of microbiome. This is the first study that shows antibiotics [are] independent of changing the biome and microbiome of the gut by changing the cells of the gut independent of bacteria, which is [a] completely new finding.”

– Ashkan Farhadi, MD

Farhadi said more research is still needed and he plans to wait for other research to reproduce this finding before changing his concepts about antibiotics.

“We believe that antibiotics only work on bacteria and not on human cells,” he added. “We have heard some reports that it affects some cells, but it [is] mainly in the form of toxicity or in that form. But this is the first study that shows it actually changes the human cells in a way that we expected only affects bacteria. So it’s different, but I think that we need more studies to back the data of this study up.”