Tetrathionate (S4O6)

Tetrathionate is an inorganic sulfur-containing anion (S4O6) that plays a pivotal role in the metabolic landscape of the inflamed gastrointestinal tract [1, 2]. In a healthy gut, tetrathionate is virtually undetectable; however, during episodes of inflammation, reactive oxygen species (ROS) released by the host immune response oxidize endogenous thiosulfate into tetrathionate [1, 3]. This molecule then serves as a high-energy electron acceptor for anaerobic respiration in specific enteric pathogens, most notably Salmonella enterica and certain Enterobacteriaceae [1, 3]. By utilizing tetrathionate, these pathogens can outcompete the resident commensal microbiota, which typically rely on less efficient fermentation processes, leading to pathogen "blooms" and worsened dysbiosis [1, 4]. Consequently, tetrathionate and its associated metabolic pathways are considered significant therapeutic targets for treating infectious diarrhea and inflammatory bowel diseases (IBD) [4]. Experimental strategies to modulate this target include the use of tungstate to inhibit tetrathionate reductase or the administration of antioxidants to prevent the initial oxidation of thiosulfate [4]. Monitoring tetrathionate levels in fecal matter may also serve as a biomarker for gut inflammatory status and the risk of pathogen overgrowth [1].

Other names

Tetrathionate anionPolythionateS4O6(2-)Tetrathionic acid

Inhibition of the molybdopterin-dependent tetrathionate reductase enzyme (TtrABC) or reduction of thiosulfate oxidation via reactive oxygen species (ROS) scavenging.