3,3-dimethyl-1-butanol and its metabolite 3,3-dimethylbutyrate ameliorate collagen-induced arthritis independent of choline trimethylamine lyase activity.

ABSTRACT: Previous studies have identified significant alterations in intestinal carnitine metabolism in mice with collagen-induced arthritis (CIA), potentially linking bacterial dysbiosis with autoimmunity. Bacterial trimethylamine (TMA) lyases metabolize dietary carnitine to TMA, which is oxidized in the liver to trimethylamine-N-oxide (TMAO). TMAO is associated with inflammatory diseases, such as atherosclerosis, whose immunologic processes mirror that of rheumatoid arthritis (RA). Therefore, we investigated the possibility of ameliorating CIA by inhibiting TMA lyase activity using 3,3-dimethyl-1-butanol (DMB) or fluoromethylcholine (FMC). During CIA, mice were treated with 1% vol/vol DMB, 100mg/kg FMC, or vehicle. DMB-treated mice demonstrated significant (>50%) reduction in arthritis severity c

SUBMITTER: Fechtner S 

PROVIDER: S-EPMC10503834 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature