Early Life Exposure to “Forever Chemicals” Disrupts Gut Microbiome, Leads to Metabolic Disorders

Researchers from The Pennsylvania State University (Penn State) have found that early life exposure to “forever chemicals” permanently disrupts the gut microbiome in mice, potentially increasing the risk of developing metabolic disease later in life. The study was published in Environmental Health Perspectives.

Establishment of the early life microbiome is crucial for human health

The development of the gut microbiome begins at birth, with the first three years of life being a critical period for its establishment. During this time, the gut is rapidly colonized by a diverse community of microorganisms that play a vital role in shaping the immune system, digestion and overall health. Disruptions to the infant microbiome can have lasting effects, contributing to the development of various health issues later in life.

Previous studies have highlighted several factors that can impact the establishment of the gut microbiome, including birth mode, diet, exposure to antibiotics and environmental factors. Recently, scientists have observed that persistent environmental pollutants, also termed “forever chemicals”, can reach the gut microbiome, affecting its composition and function.

2,3,7,8-Tetrachlorodibenzofuran (TCDF), a widespread persistent organic pollutant (POP), is a byproduct of waste incineration, metal production and the combustion of fossil fuels and wood. This pollutant can accumulate in the food chain, leading to human exposure through the consumption of high-fat foods like meat, dairy and certain fish. Infants can also be exposed to TCDF through breast milk.

“POPs are pervasive in the environment and nearly every living organism has been exposed. The negative health effects of these chemicals are well documented and include birth defects and cancer,” said corresponding author Dr. Andrew D. Patterson, a professor of Molecular Toxicology and of Biochemistry and Molecular Biology at Penn State. 

Understanding how TCDF impacts the early life microbiome is vital for preventing any potential negative long-term health effects.

TCDF permanently disrupts the gut microbiome

Mice were divided into two groups and fed pills containing either 0.46 micrograms (µg) of TCDF or a control substance for 5 days. Their gut microbiomes were then analyzed using metagenomics, NMR- and mass spectrometry-based metabolomics and biochemical assays. The researchers also measured several indicators of animal health, such as body weight, glucose tolerance, number of triglycerides in their livers and mucus in their feces, along with other markers of metabolic 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 toxicity high points, including in the gut microbiome, and begin to extrapolate what might happen at even lower doses. Of course, we also must consider how complex mixtures of these POPs interact with us and our microbial partners because a single exposure does not perfectly mimic real life scenarios,” said Patterson.

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

In a second experiment, germ-free mice were given intestinal microbiome transplants from mice that had TCDF-disrupted microbiomes. These mice later developed metabolic disorders, suggesting an altered microbiome may drive the development of metabolic disease.

TCDF impacts microbial composition

The gut microbiome composition analysis revealed a decrease in certain bacterial species, including Akkermansia muciniphila, a bacterium that is also found in the human microbiome.

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

The team administered A. muciniphila as a probiotic to the TCDF-treated mice and found it was able to restore their microbiome to its normal state.

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

Developing pre- and probiotics

“Our study is the first to suggest that early-life exposure to a certain POP, called TCDF, also disrupts the gut microbiome and is associated with metabolic disorders later in life,” said Patterson.

Mitigating TCDF exposure during early life may be essential for preserving gut microbiome health and preventing the long-term metabolic disturbances that can arise well after the chemical has left the body.

“It may be possible that with more research we could one day restore a person’s microbiome to its optimal state through supplementation with pre- and probiotics,” Patterson concluded.

Reference: Tian Y, Rimal B, Bisanz JE, et al. Effects of early-life exposures to the aryl hydrocarbon receptor ligand TCDF on gut microbiota and host metabolic homeostasis in C57BL/6J mice. Environ Health Perspect. 2024. doi: 10.1289/EHP13356

This article is a rework of a press release issued by The Pennsylvania State University. Material has been edited for length and content.