Untangling the connection among environmental exposures, the microbiome, and the gut-brain axis will be crucial to developing new strategies to prevent or treat neurological disorders, according to Anika Dzierlenga, Ph.D., of the NIEHS Division of Extramural Research and Training.

Dzierlenga, together with Jonathan Hollander, Ph.D., made the case for new research funding on this topic during a presentation to the National Advisory Environmental Health Sciences Council June 5. The Council is a congressionally mandated body that meets three times a year to advise on the direction of research, training, and career development supported by NIEHS. The Council also provides secondary review of research grant applications and provides feedback for, and approval of, new research concepts.

“A primary objective of this concept is to develop gut-focused intervention strategies — such as probiotics, microbial biomarkers, nutritional supplements, and novel therapeutics — to decrease risk, slow progression, or possibly reverse neurological conditions induced by environmental exposures,” Dzierlenga said.

Environment and the microbiome

The human microbiome is the collection of all microbes, such as bacteria, fungi, and viruses, that naturally live on our skin or inside our bodies, like in the lungs and gut. The National Institutes of Health launched the Human Microbiome Project nearly 20 years ago to learn more about how these microbes affect human health and how they interact with environmental substances to make them more or less toxic.

Thanks to these efforts, scientists now know the microbes affect signaling pathways, particularly a bidirectional pathway linking the gut microbiome to the central nervous system. This gut-brain axis may play a crucial role in neurodevelopment and neurodegenerative diseases, but research gaps and opportunities remain, according to experts who convened at recent NIEHS workshops.

There is increased evidence that environmental toxicants in the body may initiate disease progression in the brain, according to Hollander.

“In the body-first model, a toxicant is ingested, and we see pathology beginning in the gut, and it works its way to the brain stem via different pathways,” Hollander said. “The body-first approach would suggest that the gut might be an important early indicator of the disease years or potentially decades before it is diagnosed later in life.”

For example, Hollander presented data showing the pesticide paraquat affects the diversity and abundance of gut microbes in a mouse model of Parkinson’s disease. Damage to the colon wall and brain changes were evident in the model, indicating the pesticide exposure also affected signaling between the gut and brain.

“As a sensitive interface between environmental agents and neurological health, the gut-brain axis provides a novel and tractable model for exploring exposure disease pathways,” said Council member Cathrine Hoyo, Ph.D. “This program concept has the potential to catalyze transformative research across the environmental health spectrum, neuroscience, and microbiome communities.”

The Council unanimously approved the research concept, which paved the way for it to move forward as a notice of funding opportunity.

To learn more about grant recipients’ research in this area, explore this E-Factor article, podcast, and Papers of the Month highlighting the gut microbiome and gut-liver changes linked to Alzheimer’s disease. For more information about grant funding, visit grants.nih.gov.