Changes in bacterial mix linked to antibiotics increase risk for type 1 diabetes

July 24, 2018, NYU Langone Health
Credit: CC0 Public Domain

A single course of antibiotics early in childhood may increase risk for Type 1 diabetes. This is the finding of a study in mice led by researchers from NYU Medical School and published online July 24 in the journal eLife.

The study centered on the intestinal microbiome, the mix of that live in the digestive tract, and that co-evolved with humans to play roles in nutrition and immunity. As rates of children's exposure to antibiotics has increased in recent decades—with each child receiving nearly three courses on average in the first two years of life—the number of patients with type 1 has doubled, say the study authors.

In prior work, and using mice that have an unusually high rate of type 1 diabetes, the research team had found that exposure to multiple courses of antibiotics accelerated onset of this disease. The current study finds that even a single antibiotic course significantly increased risk and severity.

The normal mix of inherited microbes is thought to "educate" the founding , with evolution choosing microbes that decrease the sensitivity of , making them less likely to mistakenly attack the body's own cells, say the authors. In autoimmune diseases like type 1 diabetes, immune cells that normally control invading microbes instead destroy insulin-producing cells in the pancreas.

Patients with type 1 diabetes produce little or no insulin, the hormone that controls the level of sugar in the blood. In the current study, the onset of disease was determined by measuring blood sugar, and by marking when levels rose to extremely high levels due to the lack of insulin.

"Our findings confirm earlier work showing that antibiotics can increase risk for type 1 diabetes," says lead study author Xuesong Zhang, Ph.D., assistant professor of Medicine at NYU School of Medicine. "Even a single early life course may perturb the intestinal microbiome in ways that lead to long-term consequences in the , including immune cell changes and damage to the pancreas."

Senior study investigator Martin Blaser, M.D., director of the Human Microbiome Program at NYU School of Medicine, said the results "are a model of the pervasive effects that antibiotic courses may have on children, causing immune systems to develop abnormally on the way to serious illness."

The research team used genomic and statistical techniques to analyze the millions of pieces of bacterial DNA in samples taken from the study mice. Past studies had already matched key DNA sequences to known bacterial species, enabling the team to define each mouse's microbiome, and to watch the effect of antibiotics on each.

Specifically, the study found that four bacterial species groups (taxa) - Enterococcus, Blautia, Enterobacteriaceae, and Akkermansia—were significantly more abundant in the guts of mice treated with the single course of antibiotics, and likely involved in driving progression of type 1 diabetes. While normally harmless, such species, called pathobionts, cause disease when environmental factors like antibiotics alter the normal balance. Past studies had found that human children who later developed type 1 diabetes were more likely to have had altered gut microbiota representation of Blautia and Akkermansia mucinophila early in life, with corresponding changes to their immune systems.

The shift in dominant species seen with antibiotics was accompanied by a shift in active bacterial genes and in chemical compounds produced by the bacteria. This in turn caused changes in gene expression patterns in the intestinal wall, say the authors. Many of these genes are known to influence the type of immune cell activation that damages pancreatic islets.

In addition, populations of four different taxa—S24-7, Clostridiales, Oscillospira, and Ruminococcus—were significantly smaller in mice treated with antibiotics in comparisons with normal mice during the developmental post-birth time window previously shown to be critical to educating the immune system. The results suggest that these taxa may be protective against Type 1 diabetes, and could be a focus of future development of probiotics, for instance, that seek to restore healthy species in newborns.

The current study focused on male mice simply because it examined mechanisms found to be important in the autoimmune development regardless of gender.

The authors say their findings support the hypothesis that, by diminishing particular beneficial bacteria, one early exposure to permits the emergence of other species that change immunological development and worsen pancreatic damage.

Explore further: Antibiotic treatment increased risk for type 1 diabetes in animal study

More information: Xue-Song Zhang et al, Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity, eLife (2018). DOI: 10.7554/eLife.37816

Related Stories

Antibiotic treatment increased risk for type 1 diabetes in animal study

August 22, 2016
In doses equivalent to those used regularly in human children, antibiotics changed the mix of gut microbes in young mice to dramatically increase their risk for type 1 diabetes. That is the finding of a study led by researchers ...

Depleting microbiome with antibiotics can affect glucose metabolism

July 23, 2018
A new study from the Salk Institute has found that mice that have their microbiomes depleted with antibiotics have decreased levels of glucose in their blood and better insulin sensitivity. The research has implications for ...

Changes in bacterial mix linked to antibiotics increase risk for inflammatory bowel disease

November 27, 2017
Exposure to antibiotics in mothers may increase risk for inflammatory bowel diseases in their offspring. This is the finding of a study in mice led by researchers from NYU School of Medicine and published Nov. 27 in the journal ...

Antibiotic use increases risk of severe viral disease in mice

March 27, 2018
People infected with West Nile virus can show a wide range of disease. Some develop life-threatening brain infections. Others show no signs of infection at all. One reason for the different outcomes may lie in the community ...

Risk of type 1 diabetes climbs when one population of T cells falls

April 5, 2018
In autoimmune diseases such as type 1 diabetes, some of the immune system's T cells mistakenly attack the body's own cells, while protective T regulatory cells try to defend against that attack. Scientists at Joslin Diabetes ...

Recommended for you

Evening preference, lack of sleep associated with higher BMI in people with prediabetes

August 15, 2018
People with prediabetes who go to bed later, eat meals later and are more active and alert later in the day—those who have an "evening preference"—have higher body mass indices compared with people with prediabetes who ...

Healthy fat cells uncouple obesity from diabetes

August 14, 2018
About 422 million people around the world, including more than 30 million Americans, have diabetes. Approximately ninety percent of them have type 2 diabetes. People with this condition cannot effectively use insulin, a hormone ...

'Alarming' diabetes epidemic in Guatemala tied to aging, not obesity

August 14, 2018
The diabetes epidemic in Guatemala is worse than previously thought: more than 25 percent of its indigenous people, who make up 60 percent of the population, suffer from type 2 diabetes or pre-diabetes, suggests a new study ...

Gut reaction linked to type 1 diabetes

August 13, 2018
Understanding the link between diabetes and the gut could lead to the development of new therapies to delay the onset of type 1 diabetes, according to University of Queensland researchers.

Early age of type 1 diabetes diagnosis linked to shorter life expectancy, compared to later diagnosis

August 10, 2018
Life-expectancy for individuals with younger-onset disease is on average 16 years shorter compared to people without diabetes, and 10 years shorter for those diagnosed at an older age

Red blood cells cause cardiovascular injury in type 2 diabetes

August 7, 2018
Harmful effects of substances secreted from red blood cells could explain the increased risk of cardiovascular diseases in patients with type 2 diabetes, the results of two new studies conducted at Karolinska Institutet in ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.