Clostridium sporogenes

C. 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)^[7] – a type of auxin (plant hormone)^[8][9] – which serves as a potent neuroprotective antioxidant within the human body and brain.^{[7][10][11][12]} IPA is an even more potent scavenger of hydroxyl radicals than melatonin.^[10][11][12] Similar to melatonin but unlike other antioxidants, it scavenges radicals without subsequently generating reactive and pro-oxidant intermediate compounds.^[10][11][13] 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.^[7][14]

Tryptophan metabolism by human gut microbiota ( v t e ) 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.[12] Indole is produced from tryptophan by bacteria that express tryptophanase.[12] Clostridium sporogenes metabolizes tryptophan into indole and subsequently 3-indolepropionic acid (IPA),[7] a highly potent neuroprotective antioxidant that scavenges hydroxyl radicals.[12][10][11] IPA binds to the pregnane X receptor (PXR) in intestinal cells, thereby facilitating mucosal homeostasis and barrier function.[12] Following absorption from the intestine and distribution to the brain, IPA confers a neuroprotective effect against cerebral ischemia and Alzheimer's disease.[12] Lactobacillaceae (Lactobacillus s.l.) 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.[12] Indole itself triggers the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells and acts as a ligand for AhR.[12] 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.[12] 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.[12]

Older literature has also reported production of thiaminase I by some strains of C. sporogenes, an enzyme capable of degrading thiamine.^[15][16][17] Early studies implicated thiamine deficiency in the development of polioencephalomalacia (also known as cerebrocortical necrosis) in ruminants.^[18][19][20] However, the role of bacterial thiaminases in the development of polioencephalomalacia in ruminants remains debated.^[21]

C. sporogenes is generally regarded as a non-pathogenic anaerobe. However, rare cases of opportunistic infections have been reported in humans, including cases of bacteremia, soft tissue infection, septic arthritis, and clostridial myonecrosis.^{[22][23][24][25][26][27][28][29][30]} Similar infections have also been described in domestic animals.^{[31][32][33][34]}

Genomic and phylogenetic studies indicate that C. sporogenes is closely related to toxigenic group I clostridia (including C. botulinum)^[35] and that some strains possess the capability to produce botulism neurotoxins (BoNTs), predominantly BoNT/B serotypes.^[36][37][38] A paleogenomic study of cattle remains from a Roman-era mass grave identified a Clostridium strain phylogenetically positioned between C. sporogenes and group I C. botulinum and concluded it may represent an ancient C. sporogenes lineage which carried several virulence-associated genes, suggesting that some historical strains may have already displayed pathogenic potential.^[39]