Probiotics & Clostridium difficile

What is Clostridium difficile?

Clostridium difficile (C. difficile or C. diff) is a species of bacteria that is present naturally in the gut of around 60% of children under the age of 1 years old and 3% of adults.^1,2 C. difficile does not cause any problems in healthy people with a well balanced gut microbiota (see Probiotics Learning Lab for glossary). However, antibiotics that are used to treat other health conditions can cause dysbiosis, a condition where the normal gut microbiota is disrupted; compromising a vital part of our immune system and allowing C. difficile to multiply.

Pathogenic strains of C. difficile produce two large protein exotoxins; known simply as toxin A and toxin B.³ These toxins can induce intestinal inflammation, fluid secretion and mucosal injury.^4,5 This can result in conditions such as C. difficile-associated diarrhoea (CDAD) and, in more serious cases, colonic damage and pseudomembranous colitis.⁶

Who is at risk?

C. difficile cases occur most commonly in healthcare environments such as hospitals or care homes where patient populations are at higher risk of infection. In the hospital environment, C. difficile is the biggest known cause of infectious diarrhoea in the developed world.⁷

Recurrence

C. difficile infections are most commonly treated with met*******ole or van****cin antibiotics. Whilst this treatment is effective for most, the disease does recur after therapy in 20% of the outpatient population.⁸ In these cases, multiple recurrences are common and can be difficult to treat.⁹ Pioneering techniques such as faecal transplants,

whereby a healthy donor’s faecal matter is transplanted into a C. diff sufferer’s intestinal tract, have shown initial success in those with multiple recurrences of the disease. (Read our news piece on faecal transplants).

Scientific research on probiotics and C. difficile

A number of studies show that Saccharomyces boulardii may protect against infection and gastrointestinal inflammation induced by C. difficile.^10,11,12 One randomised, placebo controlled study revealed that S. boulardii, in combination with a standard oral antibiotic, may be more effective in decreasing the likelihood of C. difficile recurrences than standard therapy alone. The efficacy of S. boulardii was significant with a recurrence rate of just 34.6%, compared with 64.7% on placebo.¹³ In-depth research has also elucidated the mechanism of action of S. boulardii against C. difficile. Studies have shown that S. boulardii may interfere with the pathogenic process of C. difficile by releasing a 54kDa protease; which may inactivate C. difficile toxins A and B and lyse colonic receptors.^14,15 Furthermore, Saccharomyces boulardii is also known to stimulate the host’s intestinal mucosal immune response, by stimulating an increase in secretory IgA.^{16, 17}

In addition to the S. boulardii probiotic yeast, results from other clinical trials suggest that bacterial probiotics could also offer benefits for those suffering with Clostridium difficile infection (CDI).

One such randomised controlled trial monitored 33 patients who were suffering from mild to moderate Clostridium difficile infection. Patients in the intervention group were administered with a combination of four different probiotic strains: Lactobacillus acidophilus NCFM^®, Lactobacillus paracasei Lpc-37, Bifidobacterium lactis Bi-07 and Bifidobacterium lactis Bl-04. The probiotic supplement had a strength of 17 billion CFUs, and was given over a 28 day period alongside standard antibiotic treatment. Patients in the control group were given a placebo.

The results of the study showed a reduction in the duration of the infection in the probiotic group, where symptoms (typically diarrhoea) were reduced by an average of 24 hours. As patients with C. difficile are often very ill, any reduction in the duration of their symptoms is extremely significant, as the infection can significantly lower their chances of survival and can also increase the risk of infection in other patients. The incidence of C. diff infections also places a financial and practical burden on hospitals, so any safe and viable solution to conventional treatment will be welcomed by hospital administrators and staff.

Another, double-blind study observed 44 critically ill patients with aim of assessing the positive benefits of another strain, Lactobacillus plantarum 299v^® (LP299v^®), on the incidence of C. difficile infection. The study was randomised, and subjects were to be given either a dose of LP299v® or a placebo. In the placebo group there was a 19% incidence of C. difficile infection, whereas in the probiotic group, none of the patients contracted C. difficile infection.¹⁸

You can also have a look at our new Probiotics Database for further research on probiotics and C. difficile.

Article updated: 20/07/16

Article edited: 19/09/17

References:

1. NHS Statistics 17/03/2010

2. McFarland, L.V. (1999) Possible role of cross-transmission between neonates and mothers with recurrent Clostridium difficile infections. Am J Infect Control. 27: 3:301-303

3. Pothoulakis, C. (1996) Pathogenesis of Clostridium difficile-associated diarrhoea. Eur. J. Gastroenterol. Hepatol. 8:1041-1047

4. Dove, C. H. et al. (1990) Molecular characterization of the Clostridium difficile toxin A gene. Infect. Immun. 58:480-488

5. Just, I. et al. (1995) The enterotoxin from Clostridium difficile (ToxA) monoglucosylates the Rho proteins. J. Biol. Chem. 270: 11074-11078

6. Riegler, M. et al. (1995) Clostridium difficile toxin B is more potent that toxin A in damaging human colonic epithelium in vitro. J. Clin. Investig. 95:2004-2011

7. Fekety, R. (1997) Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. American College of Gastroenterology, Practice Parameters Committee. Am. J. Gastroenterol. 92: 739-750

8. Fekety, B. et al. (1989) Treatment of antibiotic-associated Clostridium difficile colitis with oral van****cin: comparison of two dosage regimens. Am J Med. 86:15-19

9. Surawicz, C. M. (2003) Probiotics, antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in humans. Best Practice & Research Clinical Gastroenterology; 17: 5; 775-783

10. Castex, F. et al. (1990) Prevention of Clostridium difficile-induced experimental pseudomembranous colitis by Saccharomyces boulardii: a scanning electron microscopic and microbiological study. J. Gen. Microbiol. 136: 1085-1089

11. Corthier, G. et al. (1986) Prevention of Clostridium difficile induced mortality in gnotobiotic mice by Saccharomyces boulardii. Can. J. Microbiol. 32: 894-896

12. Corthier, G et al. (1992) Effect of oral Saccharomyces boulardii treatment on the activity of Clostridium difficile-toxins in mouse digestive tract. Toxicon 30: 1583-1589

.13. McFarland, L. V. et al. (1994) A randomised placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. Journal of the American Medical Association. 271: 1913-1918

14. Castagliuolo, I. et al. (1999) Saccharomyces boulardii protease inhibits the effects of Clostridium difficile toxins A and B in human colonic mucosa. Infect. Immun. 67: 302-7

15. McFarland, L. V. et al. (1994) A randomised placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. Journal of the American Medical Association. 271: 1913-1918

16. Arnheim, K. (1994) Intestine-associated immune system stimulation. Saccharomyces boulardii – mechanism of action. Fortschr. Med. 112: 52-53. (In German)

17. Elmer, G. W. (1996) Biotherapeutic agents. A neglected modality for the treatment and prevention of selected intestinal and vaginal infections. JAMA 275: 870-876

18. Klarin, B. et al. (2008). Lactobacillus plantarum 299v reduces colonisation of Clostridium difficile in critically ill patients treated with antibiotics. Acta Anaesthesiol Scand, 52(8): 1096-102