Antibiotic Use in Final Stages of Pregnancy Increases IBD Risk in Offspring of Mice

Antibiotic Use in Final Stages of Pregnancy Increases IBD Risk in Offspring of Mice

Researchers at the University of Chicago Medicine found that mice genetically susceptible to developing inflammatory bowel disease (IBD) and treated with antibiotics during the final stages of pregnancy and early post-birth period had an increased risk of their offspring developing IBD.

The study, “Peripartum Exposure to Antibiotics Promotes Persistent Gut Dysbiosis, Immune Imbalance, and Colitis in Genetically Prone Offspring,” was published in the journal Cell Reports.

The antibiotic treatment altered the gut microbiome (the natural community of microbes) of mothers, suggesting that the disturbed maternal microbiome contributed to the offsprings’ increased risk for developing IBD. Notably, the adult mothers showed no increase in IBD burden, which suggests that the timing of exposure to antibiotics is crucial and early exposure can result in detrimental impacts to future generations.

“The newborn mice inherited a very altered, skewed population of microbes,” Eugene B. Chang, MD, the Martin Boyer Professor of Medicine at the University of Chicago, director of the microbiome medicine program of the Microbiome Center, and the study’s lead author, said in a press release.

These results, however, do not mean that mothers, during pregnancy or with newborn babies, should stop taking antibiotics if they have dangerous bacterial infections. Instead, they highlight the necessity for cautious assessment of antibiotic use, and that taking antibiotics “just to be safe” should be avoided.

“Antibiotics should absolutely be used judiciously when they’re indicated,” Chang said. “But we as physicians should keep in mind the importance of antimicrobial stewardship, because this study suggests that it may have long term consequences that potentially impact health and risk for certain diseases.”

Previous studies have suggested that antibiotics use during the so-called peripartum period — from late pregnancy to the nursing period after birth — increased the risk for IBD in humans, but experimental evidence was lacking.

Researchers used a standard genetic mouse model for IBD to address the impact of antibiotics during the peripartum period. They administered cefoperazone, a commonly-used antibiotic, to mice during the final stages of pregnancy and looked specifically at its effects on the immune system and microbiome.

The results showed that while mouse mothers treated with cefoperazone did not develop colitis (inflammation of the colon), their offspring exhibited a high risk for developing colon inflammation when compared to pups born from mothers without any treatment.

The microbiome of cefoperazone-treated mothers was different, showing a general decrease in the diversity of the bacterial community. Importantly, these alterations persisted for up to eight weeks after the antibiotic treatment stopped. And the alterations observed in the mothers’ microbiome were also present in their offspring, with poor microbiome diversity presenting until adulthood.

“What this should tell us is, at least as physicians, is that antibiotics are not as innocuous as we think they are, and injudicious, casual use of them can have consequences,” Chang said. “When they’re used during pregnancy or early childhood, they can disturb the development of a normal gut microbiome which would otherwise be essential for proper immune development.”

“In genetically susceptible hosts, the inability to develop the immune system properly can have negative consequences like inflammatory bowel disease or any other kinds of complex immune disorders,” he added.

Overall, these results show how alterations to the microbiome impacts the health of mothers and their future offspring.

“What we want to eventually develop is a microbial cocktail we can give to infants that ensures that they develop properly, metabolically and immunologically,” Chang said. “That’s going to have a significant impact on human health by reducing risk for many types of diseases and by promoting wellness.”