Our gut microbiome - the community of microbes in our gastrointestinal tract - helps shape our health and well-being. New research shows just how early the microbiome is built, and how antibiotics exert an influence on it. Researchers at the University of Chicago Medicine used mice with a genetic susceptibility to inflammatory bowel disease (IBD) to show that exposure to antibiotics late in pregnancy and in the early nursing period cause an increase in that IBD risk. The antibiotics had a serious impact on the fetus, but the adult mice were not affected. The research has been published in Cell Reports.
"The newborn mice inherited a very altered, skewed population of microbes," explained senior author Eugene B. Chang, MD, Martin Boyer Professor of Medicine at the University of Chicago, Director of the Microbiome Medicine Program of the Microbiome Center. "None of the mothers developed IBD, but even though they had the same genetic background, the offspring with an altered microbiome during this critical period of immune development became highly susceptible to the development of colitis." (Colitis is a type of IBD).
Since an animal model was utilized for this investigation, Chang noted that pregnant women should not avoid antibiotics they need for a serious infection because of this research. It might be yet more evidence against the casual use of antibiotics, however.
"Antibiotics should absolutely be used judiciously when they're indicated," Chang noted. "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.”
There are huge variations in the composition of the gut microbiome not only between individuals but also in the same person over time. It can be extremely challenging to demonstrate clear links between changes in the microbiome and disease susceptibility. Some research has indicated that antibiotic use in late pregnancy and just after birth raises the likelihood that a person will go on to develop IBD, but these have not been firm conclusions.
In an attempt to learn more about this relationship, postdoctoral fellow Jun Miyoshi, MD, Ph.D. and graduate student Alexandria Bobe carefully designed a mouse study. During late pregnancy and nursing, the investigators exposed groups of mice to cefoperazone, a common antibiotic. While they did not detect colitis in the antibiotic-treated adults, the pups were at a higher risk for colitis compared to pups of untreated mothers.
Genetic studies also found that antibiotics reduced both the population and the diversity of microbes in the gut. Those shifts continued in the adults for one to two months after the antibiotics were no longer being given. In the pups, there was an inheritance of the mother’s microbial populations, so the pups of antibiotic-treated mothers had a very different microbiome composition compared to pups of untreated mothers, a difference that persisted into 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."
"What this study showed is what an 'unhealthy' microbiome looks like, so presumably whatever is missing may be important to promote health," he continued. "What we want to eventually develop is a microbial cocktail we can give to infants that ensures that they develop properly, metabolically and immunologically. That's going to have a significant impact on human health, by reducing risk for many types of diseases and by promoting wellness."
If you want to know more about antibiotic use during pregnancy, check out the video above from the Mayo Clinic.