Researchers from the Karolinska Institute in Sweden and the Catalan Institute of Nanoscience and Nanotechnology (ICN2) in Spain have found that oral exposure to graphene oxide (GO) modulates the composition of the gut microbiome in adult zebrafish and can influence the crosstalk between the microbiome and immune system.
"This shows that we must factor the gut microbiome into our understanding of how nanomaterials affect the immune system," said the paper's corresponding author Bengt Fadeel, professor at the Institute of Environmental Medicine, Karolinska Institutet. "Our results are important for identifying the potential adverse effects of nanomaterial and mitigating or preventing such effects in new materials."
In the study, the researchers exposed adult zebrafish to graphene oxide via the water and analyzed how it affects the composition of the microbiome. They used both normal fish and fish lacking a receptor molecule in their intestinal cells called the aryl hydrocarbon receptor, commonly abbreviated as AhR, a receptor for various endogenous and bacterial metabolites.
"We were able to show that the composition of the gut microbiome changed when we exposed the fish to graphene oxide, even at a low dose, and that the AhR also affected the gut microbiome," said the study's first author Guotao Peng, postdoc researcher at the Institute of Environmental Medicine at Karolinska Institutet.
The researchers have also generated zebrafish larvae that completely lack a natural gut microbiome, which makes it possible to study the effects of individual microbiome components, in this case butyric acid (a fatty acid), which is secreted by certain types of gut bacteria. Butyric acid is known to be able to bind to AhR.
Doing this, the researchers found that the combination of graphene oxide and butyric acid gave rise to so-called type 2 immunity in the fish. The effect turned out to be dependent on the expression of AhR in the intestinal cells.
"This type of immunity is normally seen as a response to parasitic infection. Our interpretation is that the gut immune response can handle graphene oxide in a similar way to how it would handle a parasite," said Guotao Peng.
Using an advanced method for mapping the immune cells, the researchers were also able to show that a component of the immune system called innate lymphoid cells are found in zebrafish larvae.
"This shows that the zebrafish is a good model for studying the immune system, including the primitive or innate immune system," said Bengt Fadeel.