Oral Multiple Sclerosis Drugs Inhibit the Growth of Epsilon Toxin Producing Gut Bacterium, .

TitleOral Multiple Sclerosis Drugs Inhibit the Growth of Epsilon Toxin Producing Gut Bacterium, .
Publication TypeJournal Article
Year of Publication2017
AuthorsRumah KR, Vartanian TK, Fischetti VA
JournalFront Cell Infect Microbiol
Date Published2017
KeywordsAnti-Bacterial Agents, Clostridium perfringens, Crotonates, Dimethyl Fumarate, Fingolimod Hydrochloride, Hydroxybutyrates, Microbial Sensitivity Tests, Nitriles, Toluidines

There are currently three oral medications approved for the treatment of multiple sclerosis (MS). Two of these medications, Fingolimod, and Teriflunomide, are considered to be anti-inflammatory agents, while dimethyl fumarate (DMF) is thought to trigger a robust antioxidant response, protecting vulnerable cells during an MS attack. We previously proposed that epsilon toxin from the gut bacterium, , may initiate newly forming MS lesions due to its tropism for blood-brain barrier (BBB) vasculature and central nervous system myelin. Because gut microbiota will be exposed to these oral therapies prior to systemic absorption, we sought to determine if these compounds affect growth . Here we show that Fingolimod, Teriflunomide, and DMF indeed inhibit growth. Furthermore, several compounds similar to DMF in chemical structure, namely α, β unsaturated carbonyls, also known as Michael acceptors, inhibit . Sphingosine, a Fingolimod homolog with known antibacterial properties, proved to be a potent inhibitor with a Minimal Inhibitory Concentration similar to that of Fingolimod. These findings suggest that currently approved oral MS therapies and structurally related compounds possess antibacterial properties that may alter the gut microbiota. Moreover, inhibition of growth and resulting blockade of epsilon toxin production may contribute to the clinical efficacy of these disease-modifying drugs.

Alternate JournalFront Cell Infect Microbiol
PubMed ID28180112
PubMed Central IDPMC5263136

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