PFAS-Linked Gut Microbiome Changes May Contribute to Kidney Damage

Researchers at the Keck School of Medicine of the University of Southern California (USC) have linked per- and polyfluoroalkyl substances (PFAS) exposure to impaired kidney function, suggesting that disruptions in the gut microbiome and related metabolites linked to PFAS exposure may explain up to 50% of the observed decrease in kidney health.

Published in Science of the Total Environment, the study provides new insights into how PFAS exposure may contribute to chronic kidney disease risk, highlighting potential avenues for future interventions and policy development to protect public health.

The persistence of PFAS

PFAS are a group of manufactured chemicals that have become infamous for their longevity in the environment and the human body. Often called “forever chemicals”, PFAS are used widely in consumer products like non-stick cookware, water-resistant clothing and food packaging.

These chemicals have infiltrated ecosystems and human systems alike, and once in the body, they break down very slowly. The persistence of PFAS has been linked to a range of serious health conditions, including cardiovascular disease, cancer and chronic kidney disease.

“Nearly everyone has PFAS in their blood, and these chemicals are associated with a number of negative health effects. But we don’t have any known interventions to reduce PFAS in the body, so we can’t actually provide recommendations to help,” said lead author Dr. Hailey Hampson, a postdoctoral fellow in population and public health sciences at the Keck School of Medicine of USC.

Linking chronic kidney disease to PFAS exposure

Chronic kidney disease is a long-term condition in which the kidneys gradually lose their ability to filter waste and excess fluids from the blood, a crucial function for maintaining overall health. It affects over 10% of the global population, and over time this loss of kidney function can lead to the accumulation of toxins in the body and cause serious complications.

Despite mounting evidence linking PFAS exposure to impaired kidney function, the biological mechanisms behind this connection remain unclear. Some studies indicate that PFAS may directly affect kidney function by triggering oxidative stress, while emerging research suggests that PFAS also disrupts the balance of the gut microbiota and alters the levels of circulating metabolites – both of which are critical for maintaining healthy kidney function.

PFAS exposure decreased the abundance of beneficial gut bacteria

Longitudinal data was analyzed from 78 participants, aged between 17 and 22, enrolled in the Southern California Children’s Health Study. Blood and stool samples were collected at baseline to assess PFAS exposure, gut microbiome composition and circulating metabolites. Data on kidney function was collected four years later at a follow-up appointment. High-dimensional multiomics analyses were conducted to assess the association between the baseline PFAS exposure and the follow-up kidney function.

Hampson and the team found when PFAS exposure increased by one standard deviation, kidney function was 2.4% worse at the follow-up visit. 

The team used a statistical analysis to determine whether the gut microbiota, and its related metabolites, may be contributing to this association.

Two separate groups of bacteria and metabolites were identified that played a role in the decrease in kidney function. These groups explained between 38% and 50% of the change in function, and both groups were associated with beneficial activities in the body such as lowering inflammation.

“We saw decreases in several beneficial bacteria including bacteria from the Lachnospiraceae and Oscillospiraceae families. These bacterial changes may be related to altered metabolite levels of short chain fatty acids or other metabolites,” said Hampson speaking to Technology Networks.

“Lachnospiraceae are responsible for the production of butyric acid and propionate in the gut. These metabolites are short chain fatty acids that are involved in downregulating the expression of genes related to acute renal damage including cell cycle, oxidative stress and cell death,” she added.

The study also found that PFAS exposure was linked to elevated levels of the metabolite succinate. Although the precise mechanisms remain unknown, disruptions in the gut microbiome are known to increase succinate production, which can contribute to kidney damage by causing renal tubular injury and triggering cell apoptosis in kidney tissues.

The role of estrogen in kidney health

“It is not well defined how circulating metabolites may impact the gut microbiome and how this may impact kidney health. However, we did see that PFAS were associated with reduced levels of estrogen in our study, which may have important implications for both the gut microbiome as well as kidney health,” said Hampson.

Estrogen helps maintain the stability of the gut epithelial layer; therefore, lower estrogen levels may lead to increased gut permeability, allowing more inflammatory toxins to pass through. This effect has been linked to a higher risks of kidney damage and disease.

Identifying potential interventions and policy making

“The direct mechanism involved in these processes are still poorly understood and mechanistic studies are needed to elucidate these pathways further,” said Hampson.

Although further work is needed, Hampson is hopeful their research will begin to pave the way for identifying effective interventions.

“Based on our findings, there could be the potential for interventions that help to restore microbial balance within the gut microbiome, which could mitigate some of the changes induced by PFAS exposure. For example, dietary interventions have been shown to increase the levels of some beneficial bacteria such as Lachnospiraceae,” she said.

“Additionally, ongoing studies are exploring the potential effects of therapeutic drug interventions to help repair kidney damage induced by PFAS exposure, which could have promising effects for reducing the risk of kidney disease,” Hampson added.

The study adds to the growing evidence that new policies are needed to protect the public from the health risks associated with PFAS exposure.

“It has been well established that PFAS are very hard to remove from the body once exposed, which means that policy makers have an important role in helping to create regulations that prevent the human exposure to sources of PFAS,” Hampson concluded.

Reference: Hampson HE, Li S, Walker DI, et al. The potential mediating role of the gut microbiome and metabolites in the association between PFAS and kidney function in young adults: A proof-of-concept study. Sci Total Environ. 2024 :176519. doi: 10.1016/j.scitotenv.2024.176519

About the interviewee:

Dr. Hailey Hampson is a NIEHS T32 Environmental Genomics postdoctoral fellow at the Keck School of Medicine of USC and the University of Washington. She completed her PhD in epidemiology at the University of Southern California in 2024.