|Clostridium botulinum stained with gentian violet.|
(Metchnikoff 1908) Bergey et al. 1923
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 and is commonly found in soil. Unlike Clostridium botulinum, it does not produce the botulinum neurotoxins. In colonized hosts, it serves a symbiotic rather than pathogenic role.
In the human microbiome, C. sporogenes serves as a symbiotic bacteria that uses tryptophan to synthesize indole and then subsequently 3-indolepropionic acid (IPA) – a type of auxin (plant hormone) – which serves as an incredibly potent antioxidant within the human body and brain. IPA is an even more potent scavenger of hydroxyl radicals than melatonin. Similar to melatonin but unlike other antioxidants, it scavenges radicals without subsequently generating reactive and pro-oxidant intermediate compounds. C. sporogenes is the only bacteria known to synthesize 3-indolepropionic acid in vivo at levels which are subsequently detectable in the blood stream of the host.
It is being investigated as a way to deliver cancer-treating drugs to tumours in patients. C. sporogenes is often used as a surrogate for C. botulinum when testing the efficacy of commercial sterilisation.
- "Clostridium sporogenes". US Department of Energy. Retrieved 5 September 2011.
- Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, Siuzdak G (2009). "Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites". Proc. Natl. Acad. Sci. U.S.A. 106 (10): 3698–703. doi:10.1073/pnas.0812874106. PMC 2656143. PMID 19234110.
For example, the bacterial-mediated production of bioactive indole-containing metabolites derived from tryptophan such as indoxyl sulfate and the antioxidant indole-3-propionic acid (IPA) was impacted. Production of IPA was shown to be completely dependent on the presence of gut microflora and could be established by colonization with the bacterium Clostridium sporogenes. ... Conversely, a different set of enteric bacteria has been implicated in the metabolic transformation of indole to indole-3-propionic acid (IPA) (27). IPA, also identified only in the plasma of conv mice, has been shown to be a powerful antioxidant (28) ... Although the presence of IPA in mammals has long been ascribed in the literature to bacterial metabolic processes, this conclusion was based on either the production of IPA in ex vivo cultures of individual bacterial species (31) or observed decreases in IPA levels in animals after administration of antibiotics (32). In our own survey of IPA production by representative members of the intestinal flora, only Clostridium sporogenes was found to produce IPA in culture (Table S2). Based on these results, individual GF mice were intentionally colonized with C. sporogenes strain ATCC 15579, and blood samples were taken at several intervals after colonization. IPA was undetectable in the samples taken shortly after introduction of the microbes, and was first observed in the serum 5 days after colonization, reaching plateau values comparable with conv mice by day 10. These colonization studies demonstrate that the introduction of enteric bacteria capable of IPA production in vivo into the gastrointestinal tract is sufficient to introduce IPA into the bloodstream of the host. Also, other GF animals were injected i.p. with either IPA (at 10, 20, or 40 mg/kg) or sterile PBS vehicle, and their serum concentrations of IPA were measured over time. As seen in Table S3, the high serum levels of IPA observed 1 h after injection decreased more than 90% within 5 h, showing that IPA is rapidly cleared from the blood, and that its presence in the serum of conv animals must result from continuous production from 1 or more bacterial species associated with the mammalian gut.
IPA metabolism diagram
- Lu Q, Zhang L, Chen T, Lu M, Ping T, Chen G (2008). "Identification and quantitation of auxins in plants by liquid chromatography/electrospray ionization ion trap mass spectrometry". Rapid Commun. Mass Spectrom. 22 (16): 2565–72. doi:10.1002/rcm.3642. PMID 18655000.
- Narayanan KR, Mudge KW, Poovaiah BW (1981). "In vitro auxin binding to cellular membranes of cucumber fruits". Plant Physiol. 67 (4): 836–40. doi:10.1104/pp.67.4.836. PMC 425782. PMID 16661764.
- "3-Indolepropionic acid". Human Metabolome Database. University of Alberta. Retrieved 12 October 2015.
Indole-3-propionate (IPA), a deamination product of tryptophan formed by symbiotic bacteria in the gastrointestinal tract of mammals and birds. 3-Indolepropionic acid has been shown to prevent oxidative stress and death of primary neurons and neuroblastoma cells exposed to the amyloid beta-protein in the form of amyloid fibrils, one of the most prominent neuropathologic features of Alzheimer's disease. 3-Indolepropionic acid also shows a strong level of neuroprotection in two other paradigms of oxidative stress. (PMID: 10419516 )
- Chyan YJ, Poeggeler B, Omar RA, Chain DG, Frangione B, Ghiso J, Pappolla MA (1999). "Potent neuroprotective properties against the Alzheimer beta-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid". J. Biol. Chem. 274 (31): 21937–42. doi:10.1074/jbc.274.31.21937. PMID 10419516.
In the process of screening indole compounds for neuroprotection against Abeta, potent neuroprotective properties were uncovered for an endogenous related species, indole-3-propionic acid (IPA). This compound has previously been identified in the plasma and cerebrospinal fluid of humans, but its functions are not known. IPA completely protected primary neurons and neuroblastoma cells against oxidative damage and death caused by exposure to Abeta, by inhibition of superoxide dismutase, or by treatment with hydrogen peroxide. In kinetic competition experiments using free radical-trapping agents, the capacity of IPA to scavenge hydroxyl radicals exceeded that of melatonin, an indoleamine considered to be the most potent naturally occurring scavenger of free radicals. In contrast with other antioxidants, IPA was not converted to reactive intermediates with pro-oxidant activity. T
- Reiter RJ, Guerrero JM, Garcia JJ, Acuña-Castroviejo D (1998). "Reactive oxygen intermediates, molecular damage, and aging. Relation to melatonin". Ann. N. Y. Acad. Sci. 854: 410–24. doi:10.1111/j.1749-6632.1998.tb09920.x. PMID 9928448.
- Attwood G, Li D, Pacheco D, Tavendale M (2006). "Production of indolic compounds by rumen bacteria isolated from grazing ruminants". J. Appl. Microbiol. 100 (6): 1261–71. doi:10.1111/j.1365-2672.2006.02896.x. PMID 16696673.
- BBC News "Soil bacterium helps kill cancers."
- Development of novel biological indicators to evaluate the efficacy of microwave processing. Proquest. p. 7.
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