Study: The manganese transporter SLC39A8 links alkaline ceramidase 1 to inflammatory bowel disease (DOI: 10.1038/s41467-024-49049-8)
Researchers at the University of Michigan have delved deeper into the relationship between manganese deficiency and inflammatory bowel disease and found that low levels of the micronutrient can exacerbate intestinal injury and inflammation.
Their study, published in Nature Communications, centers around the genetic variant of the manganese transporter SLC39A8, which affects manganese levels in the body. People with a genetic variant in SLC39A8, or ZIP8, can have manganese deficiency, which this and prior studies have linked to inflammatory diseases of the intestines such as Crohn's and colitis.
"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 Young-Ah Seo, corresponding author of the study and associate professor of nutritional sciences at U-M's School of Public Health.
Manganese is essential for many physiological functions of the body, including immune responses, bone formation and carbohydrate metabolism. The mineral, which occurs in the body and in foods and other minerals, is plentiful in plant-based foods such as whole grains, legumes, rice, nuts and vegetables. However, today's animal-based diets-meat, fish, poultry, eggs, dairy products-lack sufficient amounts of manganese.
The study cites evidence that dietary consumption of manganese has decreased by more than 40% in the past 15 years in developed countries, including the United States.
That decrease and deficiency are likely linked to a rise in diseases of the bowels, say the researchers, and that manganese deficiency may be responsible for weakening the epithelial barrier of the intestines, leading to disease.
SLC39A8 is essential to regulating manganese levels, acting as the trigger for cells to take in zinc, iron, manganese, and cadmium. SLC39A8-related diseases have only recently been discovered, and the impact of the disease-associated SLC39A8 A391T variant on human health and disease is just beginning to be appreciated.
Other study co-authors include: Eun-Kyung Choi, Jin-Ho Park and Luisa Aring of the U-M School of Public of Public Health, and Thekkelnaycke Rajendiran, Chithra Muraleedharan, Vicky Garcia-Hernandez, Nobuhiko Kamada, Asma Nusrat, Tanu Soni, Linda Samuelson and Shigeki Iwase of the U-M Medical School.
