A new study led by Pennsylvania State University shows that early exposure to “forever chemicals” in the environment causes lasting damage to the gut microbiome of mice and contributes to the development of metabolic diseases later in life.

The results were published in the journal on August 14 Environmental health perspectivessuggest that human exposure to these chemicals in early childhood may contribute to the recent epidemic of metabolic diseases, including obesity and type 2 diabetes in adults.

The researchers focused in particular on 2,3,7,8-tetrachlorodibenzofuran (TCDF), a widespread persistent organic pollutant (POP) that is produced as a byproduct of waste incineration, metal production, and the combustion of fossil fuels and wood.

TCDF accumulates in the food chain. People are exposed to the substance primarily through the consumption of fatty foods such as meat, dairy products and some types of fish. Babies can be exposed to the substance through the consumption of breast milk.

“POPs are ubiquitous in the environment and virtually every living organism is exposed to them,” said Andrew Patterson, John T. and Paige S. Smith Professor of Molecular Toxicology and of Biochemistry and Molecular Biology at Pennsylvania State University.

“The negative health effects of these chemicals are well documented and include birth defects and cancer. Our study is the first to suggest that early exposure to a specific POP, called TCDF, also disrupts the gut microbiome and is associated with metabolic disorders later in life.”

The team studied the effects of TCDF in two groups of mice – a test group, those treated with TCDF, and a control group, those that received no treatment. The team fed four-week-old mice tablets containing either 0.46 micrograms (µg) of TCDF or a control tablet that did not contain TCDF for five days. Although 0.46 µg is more than the typical level in the human diet, it is not high enough to cause toxic disease.

“In our study, we used a dose that is relatively high compared to typical human exposures. However, we can use this information to identify new peaks of toxicity, including in the gut microbiome, and begin to extrapolate what might happen at even lower doses. Of course, we also need to consider how complex mixtures of these POPs interact with us and our microbial partners, as a single exposure does not perfectly mimic real-world scenarios.”

The researchers then examined the animals’ gut microbiome as well as various indicators of the animals’ health, including body weight, glucose tolerance and the amount of triglycerides in their liver and mucus in their feces, among other markers of metabolic disease.

They collected these data immediately after the five-day TCDF treatment and three months after the last dose. In humans, these time points correspond to an infant and a young adult.

“We found that early exposure to TCDF permanently disrupted the gut microbiomes of wild-type mice,” said Yuan Tian, ​​lead author and associate research professor at Pennsylvania State University. “We also found that these mice had higher body weight and glucose intolerance at four months of age.”

To further explore the effects of TCDF on the gut microbiome, the scientists administered gut microbiome transplants from mice with TCDF-disrupted microbiomes to mice without a microbiome and measured their health. They found that the mice with the transplants developed metabolic disorders, suggesting that the altered microbiome is the cause of the metabolic disease.

“These results suggest that early exposure to TCDF may impair gut microbiome function and lead to health problems later in life, even after TCDF has long been eliminated from the body,” Tian said.

She explained that gut microbiome disruptions are characterized by a decline in certain bacterial species, including Akkermansia muciniphila, a bacterium that is also typically found in the human gut microbiome.

“This is important because Akkermansia is considered important for overall gut health, but we now know that it can be negatively affected by TCDF,” Tian said.

To investigate the importance of Akkermansia muciniphila for health, the team conducted experiments by administering the bacterium as a probiotic to mice treated with TCDF. The probiotic restored the microbiome to normal.

“Our results suggest that these bacteria are affected by toxic exposure and play an important role in mediating health outcomes,” Patterson said.

“It is possible that with further research we may one day be able to restore a person’s microbiome to its optimal state by supplementing with prebiotics and probiotics.”