Per- and polyfluoroalkyl substances disrupt the gut microbiome and the balance between secondary bile acids

Diet and lifestyle 11. jul 2024 3 min Professor Matej Oresic Written by Kristian Sjøgren

A new study explores how per- and polyfluoroalkyl substances (PFAS) can affect the composition of the gut microbiome and disturb the crucial balance between secondary bile acids the microbial communities produce. A researcher says that therapy targeting the metabolism of the secondary bile acids may be one way of counteracting the harmful effects of PFAS.

The town of Korsør in Denmark was in the news when a former training area for firefighters was discovered to be heavily contaminated with PFAS. The contamination was so severe that cattle that had grazed there had unprecedentedly high concentrations, as did the people who had eaten the beef.

PFAS are demonstrably harmful to human health, but researchers have had difficulty in pinpointing exactly what PFAS do.

A new study sheds light on this, and the researchers can now show that PFAS affect the composition of gut microbial communities of people who have it in their blood, creating an imbalance between various secondary bile acids that help to maintain health.

This imbalance probably increases insulin resistance and can lead to the development of metabolic dysfunction–associated steatotic liver disease and type 2 diabetes.

“Many epidemiological studies have associated exposure to PFAS and the risk of various diseases, but identifying the mechanism by which PFAS affect health has been a challenge. We found that PFAS affect the balance between the secondary bile acids and the composition of the gut microbial communities differently among men and women,” explains a researcher behind the study, Matej Oresic, School of Medical Sciences, Örebro University, Sweden and University of Turku, Finland.

The research has been published in Environment International.

Blood and stool samples from 264 people

The study examined the blood concentrations of many toxic chemicals among 264 people – 121 men and 143 women with an average age of 57 years and an average body-mass index of 29. The researchers used stool samples to profile the gut microbial communities and measured the blood concentrations of various secondary bile acids.

Matej Oresic explains that bile acids can have positive and negative health effects. For example, the secondary bile acid lithocholic acid is generally considered to be harmful, being associated with toxicity in the liver and tumour formation.

Ursodeoxycholic acid, in contrast, is considered to promote health, since it reduces gallstones and lowers blood cholesterol levels and is being investigated for treating people with metabolic dysfunction–associated steatotic liver disease.

“The secondary bile acids are produced through microbial biosynthesis, and this is the link to the composition of gut microbes. In addition, PFAS can interact with the metabolism of the secondary bile acids, because they use the same signalling pathways. This is why PFAS are so persistent and why substances that bind to bile acids are used in treating people exposed to very high quantities of PFAS,” says Matej Oresic.

Imbalance in the secondary bile acids

The results revealed that PFAS affect the human body in different ways. Higher blood concentrations of PFAS were associated with excessive lithocholic acid and less ursodeoxycholic acid.

The researchers validated their finding by giving mice large quantities of PFAS and examined how this affected the balance between these two secondary bile acids. According to Matej Oresic, this indicates a causal connection.

In another analysis, the imbalance between the bile acids was also linearly associated with insulin resistance: the greater the imbalance, the more insulin resistance.

“This indicates that the secondary bile acids mediate the negative effects of PFAS on insulin resistance and related disorders,” explains Matej Oresic.

Disturbed gut microbes

The study also shows that PFAS negatively affect the composition of gut microbial communities, being colonised by more undesirable bacteria and fewer of those generally considered to benefit health.

The researchers also found that the sexes differed: men with high blood concentrations of PFAS had more bacteria of the species Anaerotruncus, Alistipes, Bacteroides, Bifidobacterium, Clostridium, Dorea, Eubacterium, Escherichia, Prevotella, Ruminococcus, Roseburia, Subdoligranulum and Veillonella.

Women, in contrast, typically lacked Prevotella copri bacteria when they had high blood concentrations of PFAS.

Previous studies by the researchers also found another sex difference: PFAS more strongly affect the risk of developing metabolic dysfunction–associated steatotic liver disease among women.

“We still do not know how the levels of the individual bacteria species affect health, but this shows that high concentrations of PFAS affect the composition of the gut microbiome and the relationship between the secondary bile acids and health,” adds Matej Oresic.

Possible direction for new treatments

Matej Oresic finds interesting perspectives in the new study.

The negative effects of PFAS could be counteracted by correcting the imbalance between secondary bile acids: maintaining the balance PFAS are trying to disrupt. One possibility in this direction is to try to maintain the balance by influencing the composition of the gut microbial communities.

“This involves determining how to ensure that people can excrete PFAS as rapidly as possible before they do too much damage. That is the goal, and a possible treatment may target the gut microbiome and the role of microbial communities in balancing the various secondary bile acids,” concludes Matej Oresic.

Matej Orešič holds a PhD in biophysics from Cornell University. He is a professor in medicine with a specialization in systems medicine at Örebro Univ...

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