The diversity of the gut microbiota is reduced in Wilson disease, found a new study conducted in a mouse model of the disease. Moreover, the function of amino acid, carbohydrate, and lipid metabolisms are also dysregulated as are tri- and diglyceride, phospholipid, and sphingolipid metabolisms.

Based on these findings, the study authors said that Wilson disease “should be considered a systemic disease where energy and lipid metabolism interact at an organ-specific level to modulate the phenotypic presentation.”

Read more about the pathophysiology of Wilson disease

The study was deposited in bioRxiv.

In order to explore how metabolic changes in Wilson disease affects the different tissues and the possible role of ATP7B in the metabolic dysregulation in the disease, a team of researchers led by Valentina Medici, MD, MAS, FAASLD, from the department of internal medicine, division of gastroenterology and hepatology, UC Davis in Sacramento, California, evaluated the gut microbiota and lipidome of 2 mouse models of the disease. The team also generated a new mouse model with a targeted deletion in the Atp7b gene in the intestine.

The team then analyzed the cecal content of the animals and conducted 16S sequencing and untargeted hepatic and plasma lipidome analyzes. 

They reported that the intestine-specific Atp7b mutant mice showed big changes in the desaturation of fatty acids and the metabolism of sphingolipids when challenged with a high-fat diet. They also showed altered apolipoprotein B-48 distribution in the epithelial cells of the intestine.

“Intestine-specific ATP7B deficiency affected both intestinal and systemic response to a high-fat challenge,” the researchers wrote and concluded that Wilson disease is a systemic disease where the loss of ATP7B in the intestine and diet influence phenotype.

Wilson disease is a rare genetic disease caused by a mutation in the ATP7B gene that encodes a protein that is normally responsible for transporting copper through the membranes of liver cells and secreting excess copper into the biliary system. When the protein does not function properly because of the mutation, excessive copper deposits in the liver, brain, and eyes as well as other parts of the body.


Sarode GV, Mazi TA, Neier K, et al. The role of intestine in metabolic dysregulation in murine Wilson disease. bioRxiv. Posted January 15, 2023. doi:10.1101/2023.01.13.524009