Clostridium sporogenes

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Clostridium sporogenes
Scientific classification OOjs UI icon edit-ltr.svg
Domain: Bacteria
Phylum: Bacillota
Class: Clostridia
Order: Eubacteriales
Family: Clostridiaceae
Genus: Clostridium
Species:
C. sporogenes
Binomial name
Clostridium sporogenes
(Metchnikoff 1908) Bergey et al. 1923 [1]

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 gut microbiota ()
Microbiota-derived 3-Indolepropionic acid-notext.svg
Tryptophanase-
expressing
bacteria
IPA
I3A
IPA
I3A
AhR
Intestinal
immune
cells
PXR
Mucosal homeostasis:
TNF-α
Junction protein-
coding mRNAs
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
Interactive icon.svg
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] 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. [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]

Related Research Articles

<span class="mw-page-title-main">Endospore</span> Protective structure formed by bacteria

An endospore is a dormant, tough, and non-reproductive structure produced by some bacteria in the phylum Bacillota. The name "endospore" is suggestive of a spore or seed-like form, but it is not a true spore. It is a stripped-down, dormant form to which the bacterium can reduce itself. Endospore formation is usually triggered by a lack of nutrients, and usually occurs in gram-positive bacteria. In endospore formation, the bacterium divides within its cell wall, and one side then engulfs the other. Endospores enable bacteria to lie dormant for extended periods, even centuries. There are many reports of spores remaining viable over 10,000 years, and revival of spores millions of years old has been claimed. There is one report of viable spores of Bacillus marismortui in salt crystals approximately 25 million years old. When the environment becomes more favorable, the endospore can reactivate itself into a vegetative state. Most types of bacteria cannot change to the endospore form. Examples of bacterial species that can form endospores include Bacillus cereus, Bacillus anthracis, Bacillus thuringiensis, Clostridium botulinum, and Clostridium tetani. Endospore formation is not found among Archaea.

<i>Clostridium botulinum</i> Species of endospore forming bacterium

Clostridium botulinum is a gram-positive, rod-shaped, anaerobic, spore-forming, motile bacterium with the ability to produce botulinum toxin, which is a neurotoxin.

<span class="mw-page-title-main">Tryptophan</span> Chemical compound

Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic beta carbon substituent. Tryptophan is also a precursor to the neurotransmitter serotonin, the hormone melatonin, and vitamin B3 (niacin). It is encoded by the codon UGG.

<span class="mw-page-title-main">Human microbiome</span> Microorganisms in or on human skin and biofluids

The human microbiome is the aggregate of all microbiota that reside on or within human tissues and biofluids along with the corresponding anatomical sites in which they reside, including the gastrointestinal tract, skin, mammary glands, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, conjunctiva, and the biliary tract. Types of human microbiota include bacteria, archaea, fungi, protists, and viruses. Though micro-animals can also live on the human body, they are typically excluded from this definition. In the context of genomics, the term human microbiome is sometimes used to refer to the collective genomes of resident microorganisms; however, the term human metagenome has the same meaning.

<span class="mw-page-title-main">Melatonin</span> Hormone released by the pineal gland

Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cows that could induce skin lightening in common frogs. This compound was later identified as a hormone secreted in the brain during the night, playing a crucial role in regulating the sleep-wake cycle, also known as the circadian rhythm, in vertebrates.

<i>Clostridium</i> Genus of bacteria, which includes several human pathogens

Clostridium is a genus of anaerobic, Gram-positive bacteria. Species of Clostridium inhabit soils and the intestinal tracts of animals, including humans. This genus includes several significant human pathogens, including the causative agents of botulism and tetanus. It also formerly included an important cause of diarrhea, Clostridioides difficile, which was reclassified into the Clostridioides genus in 2016.

Skatole or 3-methylindole is an organic compound belonging to the indole family. It occurs naturally in the feces of mammals and birds and is the primary contributor to fecal odor. In low concentrations, it has a flowery smell and is found in several flowers and essential oils, including those of orange blossoms, jasmine, and Ziziphus mauritiana. It has also been identified in certain cannabis varieties.

<span class="mw-page-title-main">Indole-3-acetic acid</span> Chemical compound

Indole-3-acetic acid is the most common naturally occurring plant hormone of the auxin class. It is the best known of the auxins, and has been the subject of extensive studies by plant physiologists. IAA is a derivative of indole, containing a carboxymethyl substituent. It is a colorless solid that is soluble in polar organic solvents.

<span class="mw-page-title-main">Gut microbiota</span> Community of microorganisms in the gut

Gut microbiota, gut microbiome, or gut flora are the microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut microbiota. The gut is the main location of the human microbiome. The gut microbiota has broad impacts, including effects on colonization, resistance to pathogens, maintaining the intestinal epithelium, metabolizing dietary and pharmaceutical compounds, controlling immune function, and even behavior through the gut–brain axis.

<span class="mw-page-title-main">Anthranilate synthase</span>

The enzyme anthranilate synthase catalyzes the chemical reaction

<span class="mw-page-title-main">Indole</span> Chemical compound

Indole is an organic compound with the formula C6H4CCNH3. Indole is classified as an aromatic heterocycle. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indoles are derivatives of indole where one or more of the hydrogen atoms have been replaced by substituent groups. Indoles are widely distributed in nature, most notably as amino acid tryptophan and neurotransmitter serotonin.

<span class="mw-page-title-main">Tryptophol</span> Chemical compound

Tryptophol is an aromatic alcohol that induces sleep in humans. It is found in wine as a secondary product of ethanol fermentation. It was first described by Felix Ehrlich in 1912. It is also produced by the trypanosomal parasite in sleeping sickness.

<span class="mw-page-title-main">Gut–brain axis</span> Biochemical signaling between the gastrointestinal tract and the central nervous system

The gut–brain axis is the two-way biochemical signaling that takes place between the gastrointestinal tract and the central nervous system (CNS). The term "microbiota–gut–brain axis" highlights the role of gut microbiota in these biochemical signaling. Broadly defined, the gut–brain axis includes the central nervous system, neuroendocrine system, neuroimmune systems, the hypothalamic–pituitary–adrenal axis, sympathetic and parasympathetic arms of the autonomic nervous system, the enteric nervous system, vagus nerve, and the gut microbiota.

<span class="mw-page-title-main">Urolithin</span> Group of chemical compounds

Urolithins are microflora metabolites of dietary ellagic acid derivatives, such as ellagitannins. They are produced in the gut, and found in the urine in the form of urolithin B glucuronide after absorption of ellagitannins-containing foods, such as pomegranate. During intestinal metabolism by bacteria, ellagitannins and punicalagins are converted to urolithins, which have unknown biological activity in vivo.

<span class="mw-page-title-main">6-Hydroxymelatonin</span> Chemical compound

6-Hydroxymelatonin (6-OHM) is a naturally occurring, endogenous, major active metabolite of melatonin. Similar to melatonin, 6-OHM is a full agonist of the MT1 and MT2 receptors. It is also an antioxidant and neuroprotective, and is even more potent in this regard relative to melatonin.

<span class="mw-page-title-main">3-Indolepropionic acid</span> Chemical compound

3-Indolepropionic acid (IPA), or indole-3-propionic acid, has been studied for its therapeutic value in the treatment of Alzheimer's disease. As of 2022 IPA shows potential in the treatment of this disease, though the therapeutic effect of IPA depends on dose and time of therapy initiation.

<span class="mw-page-title-main">Indolepropionamide</span> Chemical compound

Indolepropionamide (IPAM) is a chemical compound with the molecular formula C11H12N2O. In vivo (rats), IPAM markedly reduced the proton potential collapse induced by the mitochondrial toxins to nearly baseline levels in both young and old rats and demonstrated free-radical scavenging properties. IPAM was shown to increase complex I and complex IV activity in the mitochondrial electron transport chain, however complex II and complex III were left unchanged. Decreased activity of complexes I and IV results in an inhibition of electron transport that is associated with higher production of ROS. IPAM can also act as a recyclable electron and proton carrier, facilitating reversible endogenous radical and redox reactions, and thereby enabling the formation of a proton gradient that drives mitochondrial ATP synthesis. Thus, IPAM acts as a stabilizer of energy metabolism in mitochondria, thereby reducing the production of reactive oxygen species.

<span class="mw-page-title-main">Indoxyl sulfate</span> Chemical compound

Indoxyl sulfate, also known as 3-indoxylsulfate and 3-indoxylsulfuric acid, is a metabolite of dietary L-tryptophan that acts as a cardiotoxin and uremic toxin. High concentrations of indoxyl sulfate in blood plasma are known to be associated with the development and progression of chronic kidney disease and vascular disease in humans. As a uremic toxin, it stimulates glomerular sclerosis and renal interstitial fibrosis.

<span class="mw-page-title-main">Indole-3-carbaldehyde</span> Chemical compound

Indole-3-carbaldehyde (I3A), also known as indole-3-aldehyde and 3-formylindole, is a metabolite of dietary L-tryptophan which is synthesized by human gastrointestinal bacteria, particularly species of the Lactobacillus genus. I3A is a biologically active metabolite which acts as a receptor agonist at the aryl hydrocarbon receptor in intestinal immune cells, in turn stimulating the production of interleukin-22 which facilitates mucosal reactivity.

<span class="mw-page-title-main">Cyclic 3-hydroxymelatonin</span> Chemical compound

Cyclic 3-hydroxymelatonin (3-OHM) is a metabolite of melatonin and an antioxidant more potent than melatonin. It is a non-radical species and does not further propagate the radical chain reaction

References

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  2. microbeonline.com; information with figure illustrating the subterminal endospore location in the vegetative cell.
  3. BBC News "Soil bacterium helps kill cancers."
  4. Development of novel biological indicators to evaluate the efficacy of microwave processing. p. 7. ISBN   9780549830450.
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    IPA metabolism diagram
  6. 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. Bibcode:2008RCMS...22.2565L. doi:10.1002/rcm.3642. PMID   18655000.
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  8. 1 2 3 4 "3-Indolepropionic acid". Human Metabolome Database. University of Alberta. Retrieved 12 June 2018.
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  10. 1 2 3 4 5 6 7 8 9 10 11 Zhang LS, Davies SS (April 2016). "Microbial metabolism of dietary components to bioactive metabolites: opportunities for new therapeutic interventions". Genome Med. 8 (1): 46. doi: 10.1186/s13073-016-0296-x . PMC   4840492 . PMID   27102537. Lactobacillus spp. convert tryptophan to indole-3-aldehyde (I3A) through unidentified enzymes [125]. Clostridium sporogenes convert tryptophan to IPA [6], likely via a tryptophan deaminase. ... IPA also potently scavenges hydroxyl radicals
    Table 2: Microbial metabolites: their synthesis, mechanisms of action, and effects on health and disease
    Figure 1: Molecular mechanisms of action of indole and its metabolites on host physiology and disease
  11. 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 (1): 410–24. Bibcode:1998NYASA.854..410R. doi:10.1111/j.1749-6632.1998.tb09920.x. PMID   9928448. S2CID   29333394.
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