Antibiotics have made dramatic inroads in morbidity and mortality from infectious disease worldwide, but continuing use and overuse of these same agents may be contributing to the pandemic of obesity as well as dramatic increases in gastroesophageal reflux disease, type 1 diabetes, inflammatory bowel disease, asthma, and other diseases.
“If you compare maps of obesity and antibiotic use, you see a very strong association between increasing use of antibiotics and increasing obesity,” said Martin Blaser, MD, Director of the New York University Human Microbiome Program at the NYU School of Medicine. “The use of antibiotics is affecting our microbiome and our health.”
Dr. Blaser explored the latest evidence linking early antibiotic use, gut microbiome changes, and changes in human health during Missing Microbes: Lost From Our Clinics on Sunday.
He said that at least one case-controlled study found an association between pediatric antibiotic use and juvenile idiopathic arthritis. Children with five or more courses were three times more likely to develop JIA than children who received no antibiotics.
The microbiome has co-evolved with humans and developed interactive pathways that affect the central nervous system, metabolism, immune function, liver, lymphoid organs, bone marrow, and other human systems.
Antibiotic use, particularly early in life, alters the microbiome and every system with which it interacts. Macrolide antibiotics appear to disturb immune function more than beta lactam agents.
Links between antibiotic use and obesity should not be a surprise, Dr. Blaser said. Low levels of antibiotics have been used in farm animals for decades to promote growth. Mouse models show a direct link between early antibiotic use and significant increases in body fat later in life.
Antibiotic use also potentiates the weight gain seen from a high fat diet compared to a normal diet. The mechanism is changes to the microbiota. Antibiotic use favors the survival of intestinal species that shift metabolism toward increased body fat.
“Changes in the microbiota are both necessary and sufficient to change body composition,” Dr. Blaser said. “We see the same changes in germ-free mice that have never received an antibiotic but have only received the perturbed microbiota from antibiotic treated mice.”
Antibiotic use also incudes changes in ileal gene expression and immunological effectors. Work in NOD mice, which are prone to develop type 1 diabetes, showed that early life antibiotics alter intestinal gene expression. Altered gene expression affects differentiation into T-cell subtypes and enhances the development of type 1 diabetes.
“A single course of antibiotics is sufficient to accelerate the onset of type 1 diabetes in these mice,” Dr. Blaser said.
Work in colitis-prone mice not only reinforces the association between early-life antibiotic use and IBD but shows that the risk is transmitted across generations. Giving antibiotic-altered microbiota to germ-free pregnant mice increases the odds of developing colitis in their pups by 30 to 50 times.
Similarly, multiple observational studies in humans have seen a direct association between the number of courses of antibiotics given to children and their risk of developing both IBD and asthma.
Children given early antibiotics had fewer microbiota taxa known to be protective against asthma. The loss of protective taxa was even more pronounced in children whose mother had asthma.
“The well baby exam of the future will include an exam of babies and their diapers, as well,” Dr. Blaser predicted. “If their microbiome is not healthy, doctors will administer the appropriate microbes to restore their microbiome.”