Early Antibiotic Use May Raise Diabetes Risk

Could common antibiotics given to newborns be quietly shaping their long-term metabolic health?

A new study from the University of Utah Health suggests that early-life antibiotic exposure may reduce the number of insulin-producing beta cells in the pancreas, potentially increasing the risk of metabolic disorders like type 1 diabetes (T1D). Published in Science, the research could open the door to microbiome-based therapies in the future.

The rise of antibiotics and their unintended consequences

Antibiotics have been pivotal in treating bacterial infections and reducing mortality and morbidity rates. However, their widespread use has raised concerns about potential long-term health implications. Recent studies have highlighted a high prevalence of antibiotic prescriptions among young children. In 2019, an investigation found that 61% of children under 3 years received at least 1 antibiotic prescription. In low- and middle-income countries these statistics are even higher, with children receiving an average of 25 antibiotic prescriptions during their first 5 years of life.

This extensive use has sparked concerns about the appropriateness of such prescriptions and the long-term impacts of antibiotic use during childhood.

The infant gut microbiome is a complex community of microorganisms that plays an important role in immune system development and metabolic processes. Early-life antibiotic exposure can disrupt this delicate balance, leading to potential health issues. Children under the age of two who take antibiotics are at greater risk for conditions such as asthma, respiratory allergies, eczema, celiac disease, obesity and attention deficit hyperactivity disorder.

Research has also shown that such microbiome disruption may accelerate the onset of T1D, both in animal models and children, with a study finding that antibiotics prescribed in the first year of life were associated with a higher risk of T1D.

"When thinking about the commensal microbiota that live in the guts of infants, there does seem to be clear evidence that children diagnosed with T1D have fewer organisms colonizing their gut when compared to individuals that are healthy," said corresponding author Dr. June Round, a professor in microbiology and immunology at the University of Utah, when talking to Technology Networks.

Although this link between childhood antibiotic use and T1D is evident, the exact mechanisms remain unclear.

Beta cells, found in the pancreas, are responsible for producing insulin, the hormone that helps regulate blood sugar levels. Disruptions to beta cell development in infancy could have lasting effects, potentially increasing the risk of metabolic disorders such as T1D. Round and her team suspected that antibiotics, which alter the gut microbiome, might interfere with this process – leading to permanent deficits in beta cell mass and function.

With T1D cases rising globally and antibiotics commonly prescribed to infants, understanding the long-term metabolic effects of early-life microbiome disruption could have critical implications for healthcare.

Antibiotics disrupt insulin-producing cells

The researchers used a controlled mouse model, exposing newborn mice to a broad-spectrum antibiotic cocktail during a 10-day window, shortly after birth. They then tracked the development of beta cells in the pancreas using pancreatic histology and monitored the mice’s metabolic health into adulthood. They also performed RNA sequencing of islet cells to understand how microbial exposure influenced gene expression related to beta cell development.

The team found that mice exposed to antibiotics in early life developed fewer insulin-producing beta cells and had higher blood sugar levels and lower insulin levels as adults, indicating long-term metabolic impairment​.

“This, to me, was shocking and a bit scary. It showed how important the microbiota is during this very short early period of development,” said Round.

“What surprised me most was that delivery of the antibiotics during such a small window of development could have effects that lasted into adulthood,” she added.

They also found that macrophages – a type of immune cell – played a role in beta cell growth. Microbial exposure stimulated macrophage activity in the pancreas. Mice lacking macrophages failed to show the same beta cell-promoting effects, suggesting that the microbiome influences metabolism through immune signaling.

The study also examined fecal samples from human infants, collected as part of the TEDDY study. They introduced these samples into germ-free mice to see how different microbial communities affected beta cell development. Only samples from 7- to 12-month-old infants promoted beta cell growth in these mice, while samples from younger or older infants did not. This suggests that, just like in mice, humans may have a critical developmental window in which specific microbes support pancreatic beta cell expansion.

Certain microbes were also linked to healthier beta cell development. Among them, the fungus Candida dubliniensis (C. dubliniensis) stood out, as its presence in the gut was associated with greater beta cell mass and improved insulin production. C. dubliniensis is a largely unstudied fungus in the context of metabolism and it is not commonly found in healthy human adults but may be more common in infants.

Exposure to C. dubliniensis reduced the risk of T1D in male mice genetically predisposed to the condition. While mice that were colonized with a neutral microbe developed T1D 90% of the time, those exposed to C. dubliniensis developed the disease less than 15% of the time, suggesting a strong protective effect.

When researchers then introduced C. dubliniensis to antibiotic-treated mice, beta cell function improved. C. dubliniensis exposure even helped restore insulin production in adult mice that had lost beta cells, hinting at possible therapeutic applications.

Microbiome-based therapies and diabetes prevention

This study adds to a growing body of evidence that the microbiome plays a crucial role in early development. However, scientists are only beginning to understand how early microbial exposure influences metabolism, immunity and disease risk.

“We don’t know a lot about how the microbiome is impacting early-life health. But we’re finding that these early-life signals do impact early development, and then, on top of that, have long-term consequences for metabolic health,” said first author Dr. Jennifer Hill, an assistant professor in molecular cellular and developmental biology at the University of Colorado Boulder.

While the findings provide a clear biological mechanism linking antibiotics to reduced beta cell development, large-scale human studies have not yet reached a definitive conclusion.

“There have been many epidemiological studies that have looked at whether use of antibiotics is associated with T1D. The results of these studies do not provide clear evidence one way or another. Many factors affect the microbiota in children, including what kinds of organisms they receive from their parents, diet, birth mode, etc., More studies are required to understand this,” said Round.

The findings of this study do, however, raise important questions about how antibiotics are prescribed to infants. The challenge lies in balancing the need to fight bacterial infections while preserving the essential microbes that support early metabolic development.

“Antibiotics and antifungals are life-saving treatments and they are not going away,” said Round.

“One possibility in the far future is that maybe signals like these could be harnessed not only as a preventative but also as a therapeutic to help later in life,” said Hill.

The discovery that C. dubliniensis supports insulin-producing cells raises the possibility that microbial interventions could one day be used to prevent T1D or even reverse damage in adults.

“Once we identify the key organisms or molecules that can have these beneficial effects, we should be able to administer them. Currently, the only available organisms are often ones like Lactobacillus and Bifidobacteria (organisms found in yogurt) and these are not the ones that seem to have the effect in our study,” Round added.

Reference: Hill JH, Bell R, Barrios L, et al. Neonatal fungi promote lifelong metabolic health through macrophage-dependent β cell development. Science. 2025. doi: 10.1126/science.adn0953

About the interviewee:

Dr. June L. Round trained in immunology at UCLA and conducted her postdoc studies at Caltech with Sarkis Mazmanian studying how a polysaccharide on gut commensal, B. fragilis, could induce immune tolerance and protect from intestinal disease. She opened her own lab in Sept. 2011 at the University of Utah studying the interaction between the immune system and the microbiota. Her lab utilizes microbiology, immunology, bioinformatics and mouse models of disease to study this relationship.