The Clostridium bacterial genus comprises many Gram-positive, anaerobic bacterial species belonging to the Firmicutes phylum. Clostridium spp. live and act in various environments, from the soil to the human gastrointestinal tract. Although the Clostridium genus is notorious for causing human diseases, such as tetanus, botulism, and colitis, it consists of many beneficial bacteria that produce a variety of metabolites and enzymes that have utility within the realms of human health, agroecology, and biotechnology. (1)
Within the human microbiome, Clostridium spp. represent 10-40% of the total gut bacterial load. This article will consider the biodiversity of the Clostridium genus, discussing its positive impact on human health and the risk associated with pathogenic species. (1)
What Is Clostridium spp.?
Clostridium spp. is a genus of rod-shaped, Gram-positive, spore-forming anaerobic bacteria belonging to the Firmicutes phylum. The genus contains more than 100 species of bacteria, most of which are commensal to the gut microbiome. The genus is split into 19 clusters, which exist due to historical issues with taxonomic classification. Clostridium clusters IV and XIVa represent the gut's predominant Clostridial bacterial species. (2-4)
What Is the Role of Clostridium spp. in the Gut Microbiome?
Clostridium spp. play a role in gut health by directly interacting with the immune system and producing metabolites through the metabolism of starch, fiber, and proteins. Research has shown that species belonging to Clostridium clusters IV and XIVa can modify the lymphocyte profile and promote mucosal regulatory T cells within the large intestine. These results suggest that Clostridium spp. are necessary for immune homeostasis, contributing to the suppression of autoimmunity, allergy, and inflammation. (3, 5)
Clostridium spp. are also predominant short-chain fatty acid (SCFA), predominantly butyrate, producers through carbohydrate fermentation. Butyrate acts as the preferred energy source for colonic epithelial cells, exerts anti-inflammatory effects, reduces intestinal pH, supports intestinal immune function, and improves gastrointestinal barrier function. (4, 5)
Clostridium spp. are one of the commensal bacteria primarily responsible for deconjugating bile acids in the last portion of the small intestine and colon. Evidence supports that secondary bile acids block pathogenic C. difficile spore germination and cellular growth, preventing C. diff infection. (5)
What Are the Health Consequences of Unbalanced Clostridium spp. in the Gut Microbiome?
Given the benefits provided by the beneficial species of Clostridium bacteria, an imbalance and undergrowth of these bacteria can lead to the potential for the development of inflammatory and allergic bowel diseases, poor intestinal barrier, and immune function. Interestingly, an overabundance of Clostridium cluster XIVa species has been associated with irritable bowel syndrome. (4, 11)
Despite the many benefits of commensal species, a note does need to be made regarding the notorious disease-causing pathogenic Clostridium species.
C. perfringens is a spore-forming bacteria and one of the most common causes of food poisoning because of its ability to survive cooking temperatures. Toxins produced by C. perfringens are associated with acute gastrointestinal infections that range in severity from diarrhea to necrotizing enterocolitis. Symptoms of foodborne illness typically present as abdominal pain, watery and non-bloody diarrhea, and vomiting within 8-16 hours of consuming raw or uncooked meat or poultry. Rarely, an infection can progress to abdominal sepsis, which manifests with low blood pressure, fast heart rate, abnormal body temperature, and altered mental status. (6, 7)
Clostrioides difficile (formerly Clostridium difficile) infection typically occurs after antibiotic therapy. Toxin-induced damage of the colon results in diarrhea ranging in severity. In severe illness, a patient may experience up to 15 episodes of bloody, watery diarrhea daily, abdominal pain, nausea, rapid heart rate, fever, dehydration, and weight loss. Symptoms of infection usually develop within 5-10 days of starting antibiotics. Some people are C. diff carriers; they are asymptomatic but hold the potential to spread the infection to others. (8)
C. botulinum makes spores, which, when eaten, can grow and produce botulinum toxin in the gastrointestinal tract, causing adult and infant botulism. This toxin is also made by C. butyricum and C. baratii bacteria. Botulinum toxin is a neurotoxin that binds nerve receptors and inhibits the release of a neurotransmitter called acetylcholine, causing muscle paralysis. Improperly canned, preserved, and fermented foods are common sources of foodborne botulism. (9, 10)
What Causes Low Levels of Clostridium spp.?
Because the growth and metabolic activity of commensal, beneficial bacteria depend on the fermentation of fibrous carbohydrates, low-fiber and Western dietary patterns are associated with a decreased relative abundance of beneficial bacteria, including Clostridium spp., in the gut microbiome. Interestingly, the growth of Clostridium is dependent on fiber and prebiotic dose, as multiple studies show that therapeutic dosing of probiotics, prebiotics, and fiber reduces beneficial and pathogenic species of Clostridium while increasing the abundance of other beneficial bacteria. (5, 11)
What Causes High Levels of Clostridium spp.?
Cigarette smoking, coffee consumption, and high-beef diets have been associated with increased relative abundance of Clostridium spp. in human trials (2). As discussed above, Clostridium infections are associated with contaminated food/soil and antibiotic use.
How to Test Clostridium spp. Levels
Comprehensive stool analyses, such as Genova's GI Effects with Microbiomix, offer in-depth evaluation and profiling of the gut microbiome. This can be beneficial to quantify the growth of Clostridium spp. in relation to the other commensal microbiota. Stool tests, like the Vibrant Wellness Gut Zoomer 3.0 Complete and Microbiome Labs BiomeFx, will specifically identify and quantify the presence of beneficial Clostridium species and clusters for a more detailed evaluation of Clostridium growth in the large intestine.
Doctor's Data offers an anaerobic Clostridium stool culture that has the potential to detect nearly 40 beneficial and pathogenic species within the bacterial genus.
Pathogenic Clostridium infections can alternatively be diagnosed by measuring their toxins in the stool. The BioReference Labs Clostridium Difficile Cytotoxin AB is one example that can be used to test for C. diff infection.
How to Treat Clostridium spp. Imbalance
Avoidance of unnecessary antibiotics, careful handwashing, barrier use in hospitals and nursing homes, and implementing good household and cooking hygiene methods are all preventive methods for pathogenic Clostridium infections. (6, 8)
Treating Clostridium infection and restoring the healthy microbiome's normal balance may include discontinuing the inciting antibiotic for C. diff infection, antimicrobial agents (natural or pharmaceutical) with high-dose probiotics, and supportive therapy to reduce diarrhea and prevent dehydration. (12)
For patients with recurrent C. diff infection, fecal microbiota transplant (FMT) is an emerging treatment that restores healthy intestinal bacteria by placing donor stool into the colon. FMT has been shown to have a higher than 85% success rate for treating recurrent C. diff infection. (12)
Despite the many negative connotations associated with Clostridium bacterial species, most of these bugs are commensal to the human gut microbiome and confer many health benefits to regulating intestinal permeability, inflammation, and immune function. Good hygiene and antibiotic practices reduce the risk of pathogenic Clostridium infection; antimicrobial and probiotic therapies are beneficial in treating Clostridium-induced colitis and diarrhea. As scientists continue to study the nuances of the gut microbiome, emerging evidence should continue to surface regarding the probiotic roles of beneficial Clostridium spp.
Lab Tests in This Article
1. "Clostridium - an Overview." Science Direct, www.sciencedirect.com/topics/agricultural-and-biological-sciences/clostridium.
2. Commensal Bacteria. (2022). Genova Diagnostics. https://www.gdx.net/core/supplemental-education-materials/Commensal-Bacteria-Chart.pdf
3. Lopetuso, L.R., Scaldaferri, F., Petito, V., et al. (2013). Commensal Clostridia: leading players in the maintenance of gut homeostasis. Gut Pathogens, 5(1), 23. https://doi.org/10.1186/1757-4749-5-23
4. Grenda, T., Grenda, A., Domaradzki, P., et al. (2022). Probiotic Potential of Clostridium spp.—Advantages and Doubts. Current Issues in Molecular Biology, 44(7), 3118–3130. https://doi.org/10.3390/cimb44070215
5. Guo, P., Zhang, K., Ma, X., et al. (2020). Clostridium species as probiotics: potentials and challenges. Journal of Animal Science and Biotechnology, 11(1). https://doi.org/10.1186/s40104-019-0402-1
6. CDC. (2018, October 2). Clostridium perfringens (C. perfringens). Centers for Disease Control and Prevention. https://www.cdc.gov/foodsafety/diseases/clostridium-perfringens.html
7. Yao, P., & Annamaraju, P. (2020). Clostridium Perfringens. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK559049/
8. Mayo Clinic. (2021, August 27). C. difficile infection - Symptoms and causes. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/c-difficile/symptoms-causes/syc-20351691
9. Wells, C.L., & Wilkins, T.D. (2019). Clostridia: Sporeforming Anaerobic Bacilli. Nih.gov; University of Texas Medical Branch at Galveston. https://www.ncbi.nlm.nih.gov/books/NBK8219/
10. CDC. (2021, June 1). About Botulism. Centers for Disease Control and Prevention. https://www.cdc.gov/botulism/general.html
11. Singh, R.K., Chang, H.W., Yan, D., et al. (2017). Influence of diet on the gut microbiome and implications for human health. Journal of Translational Medicine, 15(1). https://doi.org/10.1186/s12967-017-1175-y
12. Mayo Clinic. (2016). C. difficile infection - Diagnosis and treatment. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/c-difficile/diagnosis-treatment/drc-20351697