Clostridium sporogenes

Clostridium sporogenes is a species of Gram-positive bacteria that belongs to the genus Clostridium. Like other strains of Clostridium, it is an anaerobic, rod-shaped bacterium that produces oval, subterminal endospores[2] and is commonly found in soil. Unlike Clostridium botulinum, it does not produce the botulinum neurotoxins. In colonized animals, it has a mutualistic rather than pathogenic interaction with the host.

It is being investigated as a way to deliver cancer-treating drugs to tumours in patients.[3] C. sporogenes is often used as a surrogate for C. botulinum when testing the efficacy of commercial sterilisation.[4]

Clostridium sporogenes colonizes the human gastrointestinal tract, but is only present in a subset of the population; in the intestine, it uses tryptophan to synthesize indole and subsequently 3-indolepropionic acid (IPA)[5] – a type of auxin (plant hormone)[6][7] – which serves as a potent neuroprotective antioxidant within the human body and brain.[5][8][9][10] IPA is an even more potent scavenger of hydroxyl radicals than melatonin.[8][9][10] Similar to melatonin but unlike other antioxidants, it scavenges radicals without subsequently generating reactive and pro-oxidant intermediate compounds.[8][9][11] C. sporogenes is the only species of bacteria known to synthesize 3-indolepropionic acid in vivo at levels which are subsequently detectable in the blood stream of the host.[5][12]

Tryptophan metabolism by human gastrointestinal microbiota () Tryptophan Clostridium sporogenes Lacto- bacilli Tryptophanase- expressing bacteria IPA I3A Indole Liver Brain IPA I3A Indole Indoxyl sulfate AST-120 AhR Intestinal immune cells Intestinal epithelium PXR Mucosal homeostasis: ↓TNF-α ↑Junction protein- coding mRNAs L cell GLP-1 T J Neuroprotectant: ↓Activation of glial cells and astrocytes ↓4-Hydroxy-2-nonenal levels ↓DNA damage –Antioxidant –Inhibits β-amyloid fibril formation Maintains mucosal reactivity: ↑IL-22 production Associated with vascular disease: ↑Oxidative stress ↑Smooth muscle cell proliferation ↑Aortic wall thickness and calcification Associated with chronic kidney disease: ↑Renal dysfunction –Uremic toxin Kidneys This diagram shows the biosynthesis of bioactive compounds (indole and certain other derivatives) from tryptophan by bacteria in the gut.[10] Indole is produced from tryptophan by bacteria that express tryptophanase.[10] Clostridium sporogenes metabolizes tryptophan into indole and subsequently 3-indolepropionic acid (IPA),[5] a highly potent neuroprotective antioxidant that scavenges hydroxyl radicals.[10][8][9] IPA binds to the pregnane X receptor (PXR) in intestinal cells, thereby facilitating mucosal homeostasis and barrier function.[10] Following absorption from the intestine and distribution to the brain, IPA confers a neuroprotective effect against cerebral ischemia and Alzheimer's disease.[10] Lactobacillus species metabolize tryptophan into indole-3-aldehyde (I3A) which acts on the aryl hydrocarbon receptor (AhR) in intestinal immune cells, in turn increasing interleukin-22 (IL-22) production.[10] Indole itself triggers the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells and acts as a ligand for AhR.[10] Indole can also be metabolized by the liver into indoxyl sulfate, a compound that is toxic in high concentrations and associated with vascular disease and renal dysfunction.[10] AST-120 (activated charcoal), an intestinal sorbent that is taken by mouth, adsorbs indole, in turn decreasing the concentration of indoxyl sulfate in blood plasma.[10]