Scientists have found a link between manganese deficiency and both inflammatory bowel disease (IBD) and increased inflammation and damage in the intestine. Manganese is an essential nutrient that is primarily found in whole grains, legumes, nuts, rice, and vegetables. Manganese has a variety of important roles in the body, including aiding blood clotting, bone maintenance, and many aspects of metabolism. Dietary consumption of manganese is thought to have declined by as much as 40 percent in developed countries over the past fifteen years. Diets that are high in meats, processed grains and sugars are thought to be one reason for this decline. A lack of manganese has been shown to cause intestinal damage in a mouse model, and epidemiological research has suggested that IBD and manganese deficiency are connected in people.
IBD includes Crohn’s disease and ulcerative colitis, and the causes are unclear, but are thought to be a complex mix of genetic, environmental, and microbial factors. These disorders can cause intestinal damage that makes the gut lining become excessively permeable, which can cause a variety of problems, and can impair the uptake of essential nutrients. The gut lining, or epithelium, is also closely connected to immunity. When the gut epithelium is damaged, it can lead to inflammation in the gut and throughout the body.
Now, scientists have shown that a small change in the sequence of a gene, or variant, can lead to low manganese levels. The genetic variant occurs in a gene called SLC39A8 or ZIP8, which encodes for a manganese transporter. Carriers of this variant were found to often have manganese deficiency.
Reporting in Nature Communications, researchers have shown that SLC39A8 is a crucial regulator of manganese levels, and can cause cells to not only absorb manganese, but also cadmium, iron, and zinc. The gene is expressed in liver cells, where ir probably absorbs the nutrient from bile.
This study deetermined that when intestinal manganese levels are at the right place, the organ is protected from injury. But if appropriate manganese levels are disrupted, the epithelial barrier is susceptible to damage and inflammation, leading to an increase in the risk of IBD.
"Our research reveals the crucial role of the manganese transporter SLC39A8 in maintaining healthy manganese levels and intestinal health. Our work also opens new therapeutic possibilities for IBD patients linked to manganese imbalance," said corresponding study author Young-Ah Seo, an associate professor of nutritional sciences at the University of Michigan School of Public Health.
Sources: University of Michigan, Nature Communications
