Metabolic factors play a role in an array of human conditions, including autism, said researchers at the June 8 webinar in the Early-Stage Investigator (ESI) Spotlight Series. Zhanghua Chen, Ph.D., discussed her research on how air pollution exposure changes human metabolism in ways that can cause or worsen disease. Maude David, Ph.D., spoke about how she studies autism by capturing metabolic and microbiome data.

The webinars showcase early-career researchers at institutions affiliated with the NIEHS Environmental Health Science Core Centers. Maria José Rosa, Dr.P.H., and Douglas Walker, Ph.D., of the Mount Sinai Transdisciplinary Center on Early Environmental Exposures, host the monthly lectures.

Air pollution and disease

Chen described recent studies that suggest air pollution can change how the body metabolizes amino acids, fatty acids, and lipids. These changes can, in turn, contribute to the onset of various diseases.

She is an assistant professor with the Southern California Environmental Health Sciences Center (SCEHSC) in the Keck School of Medicine at the University of Southern California. Her laboratory has studied key chemical reactions of metabolism in adults and children exposed to traffic-related air pollution in California.

“To understand what metabolic pathways were altered by air pollution exposure, we chose to study metabolomics, which is a tool to analyze small molecules such as metabolites in peripheral systems and tissue samples,” Chen said.

Through a series of studies, Chen and her team found both short- and long-term air pollution exposure may be associated with increased risk of metabolic dysfunctions that result in diabetes, obesity, worsening asthma, and higher instances of autism.

Chen aims to show that air pollution exposure directly changes metabolic pathways, thus causing disease. She also plans to contribute to solutions for pollution-related health problems. Ultimately, she hopes to investigate how well air purifiers reduce personal pollution exposure and to find ways to disrupt the progress of diseases and syndromes caused by air pollution.

Microbiome, metabolites, and the mind

In her talk, David described how her laboratory is investigating potential links between metabolism and autism spectrum disorder. David is an assistant professor at Oregon State University (OSU) and a member of the Environmental Health Sciences Center at OSU.

David heads the David Laboratory at OSU, where she studies the gut-brain axis to understand how microbes might impact behavior, specifically in autism spectrum disorder and anxiety. (Photo courtesy of Maude David)

In her study, David and her colleagues recruited more than 100 families with two children, within two years of age of each other, one diagnosed with autism and one developing typically. They analyzed stool samples taken from the children over time, to find differences in the types of gut microbes and metabolites between siblings.

David and her team identified some differences. Notably, they found lower levels of a metabolite called 5-dodecenoate (5D) — a medium-chain fatty acid — in the autistic siblings’ stool.

To follow-up on this finding, the team looked at mice whose biology had been altered to mimic some autism symptoms. They gave these mice 5D orally, then placed them in lab environments that normally stress autism-mimicking mice. The mice given 5D, however, showed signs of lower anxiety and became more sociable with other mice. If these signs translated to humans, they would represent improvements in autism symptoms.

“Our working hypothesis is that autism has associations with metabolic dysfunctions that will impact cellular energy production,” said David. To investigate this hypothesis, her group looked at a special class of lipids known as cardiolipins, which are composed of fatty acid chains and help make energy in cells.

They analyzed lipids from the livers and plasma of the autism-mimicking control mice. There, they found significantly lower levels of the most usable form of cardiolipin. In the treated mice, however, the doses of 5D seemed to raise the usable cardiolipin levels, resolving the metabolic issues.

David believes that the availability of medium- and long-chain fatty acids in the body may have a large impact on the gastrointestinal and behavioral features of autism. She hopes to validate the experiment results and investigate possible dietary or microbial sources of 5D as potential therapies for the condition.

(Lee Cannon is a contract writer for the NIEHS Office of Communications and Public Liaison.)