A Potential Miracle Cure Touted for Clostridium Difficile

Although the incidence of hospital-acquired C. diff. in Canada decreased from 5.9 per 10 000 patient-days in 2009 to 4.3 in 2015 according to a recent study¹, this is small consolation to affected patients. The burden of severe or recurrent episodes of antibiotic-resistant Clostridium difficile infection (CDI) on individuals is debilitating, and can be fatal.

Fecal Microbial Transplantation (FMT) or the transplantation of stool material has been touted as a 'miracle cure'² for patients with severe or recurrent infections of C. diff. Patients at the University of Alberta Hospital, one of the few in Canada with a FMT Program, who received a transplant of fecal material have returned to normal within one to three days of the procedure³. FMT may prove to be an important treatment option for patients with antibiotic-resistant C. diff. non-responsive to conventional therapy.

Fecal transplantation
Today's treatment has evolved to today's techniques of fecal microbiota transplantation, via a number of different routes, in patients with severe and recurrent antibiotic-resistant C. diff. Transplantation of FMT is not difficult; it involves the transplantation of fecal material from the gut of a healthy individual, by colonoscopy, enema or other means, into the gut of individuals with C. diff. This restores the bacteria that has been killed or suppressed, usually by antibiotic therapy. The gut contains a microbiome (collection of microbes) of bacteria, viruses, fungi and single celled micro-organisms that interact to aid digestion, regulate the immune system, protect against disease and manufacture vital vitamins.

One of the early proponents of FMT treatment is Thomas Borody, a gastroenterologist practicing in Sydney, Australia. Borody began providing FMT services in 1988⁴, and has treated patients with diverse gastrointestinal conditions including: Crohn's disease; ulcerative colitis; and C. diff.  North America is far more restrictive; with increased public interest (and pressure) in using FMT as an alternative strategy for treating severe or recurrent CDI, both the FDA⁵ (in 2013) and Health Canada⁶ (in 2015) published guidelines for FMT. In Canada, the use of FMT is currently limited to C. diff; a clinical trial authorized by Health Canada is the only context when FMT may be used for other indications (e.g., ulcerative colitis).

Is DIY ("do it yourself") an option?
Due to the growing online media hype around the benefits of FMT, there are also numerous websites (not for the faint hearted) that describe how you can carry out DIY transplants. Some of the interest in DIY may be due to lack of access to an FMT clinic, the cost of therapy through private clinics, and/or the desire to use FMT for treating conditions (such as obesity and autism) that are not approved by current Health Canada or FDA regulations.

While consumers' paramount interest may be ready access to FMT for treating a range of gastrointestinal conditions, clinicians and regulators are alarmed about the absence of DIY's safety.  The consumer using unscreened family member's and/or friend's donations of stool for FMT is ignoring the possible risk of exposure to diseases such as HIV or hepatitis. Screening healthy donors and their fecal material is imperative to identifying the presence of known pathogens, but even this screening may fail to detect all potential risks.

FMT as an alternative to antibiotics
FMT marks a large change from how clinicians treat infectious diseases which has been mainly with antibiotics and vaccines. The unintended consequence of eliminating infectious diseases this way though is the emergence of a host of antimicrobial resistance (AMR) bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). These pathogens can be fatal is not treated appropriately.

Canada currently has a number of surveillance programs that track antibiotic use and AMR, including the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) and Canadian Nosocomial Infection Surveillance Program (CNIPS).  These programs in concert with provincial, territorial and local initiatives have reduced antibiotic use as the first line of treatment for most people with coughs and colds. As antibiotics disrupt the intestinal microbiota, part of the solution to tackling AMR includes protecting the gut's microbiota against the negative effects of antibiotics⁷ through strategies such as FMT. This is particularly important for older people who are at increased risk of developing chronic and recurrent CDI.

So what does the future hold for treating CDI?
Gut bacteria is fundamental to an individual's health and wellbeing. Research has shown the gut's microbiota can be manipulated by active (i.e., antibiotic, probiotics etc.) and passive (i.e., lifestyle and diet changes) means⁸.  FMT has successfully treated CDI unresponsive to antibiotics by changing the gut's microbiota; this is a crucial part of the emerging trend of creating next generation probiotics (usually isolated from a populations' gut microbiota). This may mean that the first line of treatment for diseases will not be with antibiotics but by administering genetically modified microbes. These microbes would be specifically selected to complement the health status of the host to fight infection as well as actively target certain diseases.

It is known that microbiome manipulation can significantly influence health, as seen with C. diff., this presents an exciting opportunity to use these gut organisms as therapeutic agents⁹. This has become an emerging area of research in health and life sciences industries, and could lead to the refinement of FMT to a more targeted therapy. The implications of microbiome manipulation have vast potential not only in infectious diseases management but also as a strategy for other conditions such as obesity and diabetes.

Blog created for Canada. Reference: Leigh-Wood, M. Trends in Health and Life Sciences: When waste isn't wasted – A Detailed Review (Insights/Blog Post). Retrieved from: http://www.cnahardy.com/news-and-insight/insights/english/trends-in-healthcare-and-life-sciences-detail

¹ Katz, K et al, The evolving epidemiology of Clostridium difficile infection in Canadian hospitals during a postepidemic period (2009–2015), CMAJ, June 20, 2018, retrieved at http://www.cmaj.ca/content/190/25/E758.
² Fecal Microbiota Transplantation Miracle cure restores healthy digestive system, University Hospital Foundation, Alberta.
³ Ibid.
⁴ Centre for Digestive Diseases, About Thomas Borody, retrieved from https://centrefordigestivediseases.com/about-us/professor-thomas-borody/.
⁵ Food and Drug Administration(2013), Guidance for Industry, Enforcement Policy Regarding Investigational New Drug Requirements for Use of Fecal Microbiota for Transplantation to Treat Clostridium difficile Infection Not Responsive to Standard Therapies, updated 2016, retrieved from https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-regarding-investigational-new-drug-requirements-use-fecal-microbiota.
⁶ Health Canada (2015), Guidance Document: Fecal Microbiota Therapy Used in the Treatment of Clostridium difficile Infection Not Responsive to Standard Therapies, retrieved at https://www.canada.ca/en/health-canada/services/drugs-health-products/public-involvement-consultations/biologics-radiopharmaceuticals-genetic-therapies/guidance-document-regulation-fecal-microbiota-therapy.html.
⁷ Ruppé, L., Burdet C. et al, Impact of antibiotics on the intestinal microbiota needs to be re-defined to optimize antibiotic usage, retrieved from https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(17)30530-X/fulltext.
⁸ Hage, R., Hernandez-Sanabria, and Van de Wiele, T., Emerging Trends in "Smart Probiotics": Functional Consideration for the Development of Novel Health and Industrial Applications (2017), retrieved at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626839/.
⁹ Balcus, E., The Human Microbiome (2018), retrieved from https://pubs.acs.org/doi/full/10.1021/acsinfecdis.7b00248.