Sarcoidosis patients appear to have unusual energy production and transmethylation of proteins, as well as an abnormal gut microbiota, according to researchers at Wayne State University School of Medicine and colleagues, who compared the metabolites found in sarcoidosis patients with those of healthy people.
The study, “Metabolomics connects aberrant bioenergetic, transmethylation, and gut microbiota in sarcoidosis,” published in Metabolomics, may lead to the development of new drugs against the disrupted pathways or to the implementation of measures, such as nutritional modification, that affect metabolite production.
Sarcoidosis is a granumomatous disease of unknown cause that manifests with a variety of symptoms, depending on the affected organ. It is an inflammatory disease characterized by the presence of activated macrophages and the expansion of T-cells and B-cells that contribute to granuloma formation, ultimately affecting in organ function. This suggests that patients with sarcoidosis have a sustained activation of inflammatory pathways.
Metabolites, the end products of cellular metabolic processes, are considered the ultimate response of an organism to environmental and genetic factors, and recent studies have shown that metabolic reprogramming is required for inflammation and immunological responses to diverse stimuli. However, how metabolic alterations associate with the sustained inflammation of sarcoidosis has not been studied.
Researchers analyzed the metabolomic profiles of sarcoidosis patients, using a technique called 1H NMR spectroscopy, and compared them to the profiles of healthy controls.
Their analysis revealed that the levels of metabolites — such as 3-hydroxybutyrate, acetoacetate, carnitine, cystine, homocysteine, pyruvate, and trimethylamine N-oxide — were significantly increased in sarcoidosis patients. In addition, researchers found that succinate, a major intermediate metabolite of the Krebs cycle, was significantly decreased in patients with sarcoidosis.
The researchers were able to detect the altered metabolites in three critical pathways, including two energy production pathways, and a pathway involved in protein modification, or transmethylation. High levels of homocysteine, a component of the transmethylation pathway, has already been associated with immune cell function, possibly by inducing monocyte and T-cell activation.
Data also pointed toward aberrant microbiota, as some of the metabolites involved in increased levels of inflammation come from bacteria metabolism.
Although further studies are required to understand exactly how the modified metabolites participate in the inflammatory status and development of sarcoidosis, the researchers believe that metabolomics may become a critical tool for gaining better insight into this disease.