The same metabolite is connected to metabolic and cardiovascular diseases.
Recent research reveals that a substance produced by gut microorganisms can cause scarring and blood vessel damage in scleroderma patients.
The gut microbiome modulates immunity, and changes in it have a role in autoimmune disorders like scleroderma. Researchers did not know how changes in the intestinal microbiome contribute to the fibrosis and vascular damage seen in scleroderma until recently.
Researchers from Michigan Medicine explored how a compound called trimethylamine N-oxide, or TMAO, produced by the gut microbiome may alter cellular processes in scleroderma, causing fibrosis, inflammation, and vascular damage.
TMAO is generated in the liver when the stomach metabolizes nutrients like choline and carnitine, which are abundant in a meat-rich Western diet. According to findings published in iScience, the TMAO can reprogram cells to become scar-forming myofibroblasts, resulting in fibrosis and vascular damage. Furthermore, FMO3, the enzyme responsible for the production of TMAO, is elevated in scleroderma patients.
“We have uncovered a novel mechanism linking the Western diet, the gut microbiome, and some of the devastating effects of scleroderma,” said John Varga, M.D., senior author of the paper and chief of the Division of Rheumatology at the University of Michigan Health. “We will next examine whether drugs or food products like virgin olive oil, can be used to block the formation of this compound in the gut to treat fibrosis.”
Reference: “Gut microbe-derived metabolite trimethylamine N-oxide activates PERK to drive fibrogenic mesenchymal differentiation” by Seok-Jo Kim, Swarna Bale, Priyanka Verma, Qianqian Wan, Feiyang Ma, Johann E. Gudjonsson, Stanley L. Hazen, Paul W. Harms, Pei-Suen Tsou, Dinesh Khanna, Lam C. Tsoi, Nilaksh Gupta, Karen J. Ho and John Varga, 24 June 2022, iScience.
The study was funded by the National Institutes of Health.