Fecal Microbiota Transplantation: A Potential Treatment for Crohn’s Disease: Difference between revisions

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Crohn's disease (CD) is a relapsing inflammatory disease that is associated with autoimmune disorders. It affects the gastrointestinal tract and symptoms often include abdominal pain, diarrhea of mucus or blood, fever, and weight loss (Baumgart and Sandborn, 2012). There is currently no available treatment to cure this chronic illness, therefore long-term treatment is often used even though there are concerns regarding long-term use of various drugs prescribed to manage CD (Baumgart and Sandborn, 2012). When CD treatment has been exhausted, fecal microbiota transplantation may be a promising rescue therapy.
Crohn's disease (CD) is a relapsing inflammatory disease that is associated with autoimmune disorders. It affects the gastrointestinal tract and symptoms often include abdominal pain, diarrhea of mucus or blood, fever, and weight loss (Baumgart and Sandborn, 2012). There is currently no available treatment to cure this chronic illness, therefore long-term treatment is often used even though there are concerns regarding long-term use of various drugs prescribed to manage CD [http://www.sciencedirect.com/science/article/pii/S0140673612600269]. When long-term CD treatment has been exhausted, fecal microbiota transplantation may be a promising rescue therapy.  
   
   
Fecal microbiota transplantation (FMT) is a procedure in which fecal matter is collected from a healthy donor, mixed with a saline or other solution, strained, and placed in a patient via colonoscopy, endoscopy, sigmoidoscopy, or enema. Prior to 2013, research that explored the treatment efficacy of FMT was generally limited to patients with Clostridium difficile infections (CDI) but over the last few years, FMT has increasingly become a popular inquiry among patients with  inflammatory bowel diseases(IBD) other than CDI (Colman and Rubin, 2014).  
Fecal microbiota transplantation (FMT) is a procedure in which fecal matter is collected from a healthy donor, mixed with a saline or other solution, strained, and placed in a patient via colonoscopy, endoscopy, sigmoidoscopy, or enema. Prior to 2013, research that explored the treatment efficacy of FMT was generally limited to patients with Clostridium difficile infections (CDI) but over the last few years, FMT has increasingly become a popular inquiry among patients with  inflammatory bowel diseases(IBD) other than CDI. [http://www.sciencedirect.com/science/article/pii/S1873994614002438]





Revision as of 11:48, 26 March 2015

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Crohn's disease (CD) is a relapsing inflammatory disease that is associated with autoimmune disorders. It affects the gastrointestinal tract and symptoms often include abdominal pain, diarrhea of mucus or blood, fever, and weight loss (Baumgart and Sandborn, 2012). There is currently no available treatment to cure this chronic illness, therefore long-term treatment is often used even though there are concerns regarding long-term use of various drugs prescribed to manage CD [1]. When long-term CD treatment has been exhausted, fecal microbiota transplantation may be a promising rescue therapy.

Fecal microbiota transplantation (FMT) is a procedure in which fecal matter is collected from a healthy donor, mixed with a saline or other solution, strained, and placed in a patient via colonoscopy, endoscopy, sigmoidoscopy, or enema. Prior to 2013, research that explored the treatment efficacy of FMT was generally limited to patients with Clostridium difficile infections (CDI) but over the last few years, FMT has increasingly become a popular inquiry among patients with inflammatory bowel diseases(IBD) other than CDI. [2]


History


FMT has been a treatment in traditional Chinese medicine since as early as the 4th century. “Zhou Hou Bei Ji Fang” (meaning “Handy Therapy for Emergencies”), the first Chinese handbook of emergency medicine, accounted for the success of the first FMT cases by famous traditional Chinese medicine doctor Ge Hong. He lived during the Dong-jin Dynasty and used human fecal suspension to treat patients who had food poisoning or severe diarrhea (Zhang et al. 2012). The second record of FMT being used to treat physical illnesses was from the 16th century Ming Dynasty. In the most famous traditional Chinese medicine book “Ben Cao Gang Mu ” (meaning “Compendium of Materia Medica”), Li Shizhen, another well-known eastern medicine doctor, described a series of prescriptions using fermented fecal solution, fresh fecal suspension, dry feces, or infant feces for effective treatment of abdominal diseases with severe diarrhea, fever, pain, vomiting, and constipation. Treatments containing fecal matter were labeled as “yellow soup” and other names for aesthetics (Zhang et al. 2012).





Case Study

The first FMT for severe enterocolonic CD
A 32-year-old Chinese man developed severe enterocolonic CD where he was hospitalized in 2012 for progressive abdominal pain, bloody and purulent diarrhea and high fever of 38 °C-39.5 °C. He was diagnosed in 2010 and managed his disease through daily intravenous medicines. A CT Scan showed an abdominal mass of size 14 cm × 8 cm × 10 cm. His sigmoid colon was severely inflamed and he was given intravenous antiobiotics for 10 days but frequently experienced fever and abdominal pain; plus, the abdominal mass size was unchanged. After the patient expressed interest in a clinical trial, various tests were conducted and the donor found was his 10-year-old, healthy daughter. A week after FMT, his previous symptoms were dramatically alleviated and the size of inflamed mass was reduced. Additionally, the CDAI score was reduced to 228. He had a severe cold in the whole third week after he was discharged with clinical improvement. At one month of follow-up after FMT, his CDAI score was further reduced to 143, which met the criteria of clinical remission. To that effect, three months after FMT, the CDAI score was further reduced to 62, suggesting sustained clinical remission. His appetite improved, album total cholesterol increased to 47.5 g/L (within normal range of 35-55) and he gained 11 kg in nine months (Zhang et al. 2013).

Methods of the First Standardized FMTs in China

Donor Screening
Patients can self-identify potential donor or the doctor can recommend fecal microbiota from the bacterial bank. The medical and surgical history are necessary. The volunteers who had passed the selection criteria are given a laxative before defecation.

Patient preparation
Conventional treatment of CD is stopped one week prior to FMT. Disease duration, disease localization, disease behavior, treatment and surgical history, body weight, and Harvey–Bradshaw Index (HBI) are assessed. Peripheral blood is collected for chemical and biological analyses.


FMT procedure


Safety of FMT and endoscopic procedure
In a case study following 49 patients who received FMT through the mid-gut, there was no severe or obvious adverse events during endoscopic infusion after FMT and long-term follow-up of 6-15 months.

FMT-Related Factors
Genetic background or close contact with recipients did not significantly affect the outcome of patients’ clinical response at six months after FMT. The efficacy of using fresh fecal microbiota seemed higher than that using frozen fecal microbiota, but the difference on the clinical improvement or clinical remission was not significant. There were no differences in patients’ clinical response between the two age groups of donors over 14 and under 14 years of age.

Further Reading

Understanding the jiaoqi Experience: The Medical Approach to Illness in Seventh-century China—Centers for Disease Control and Prevention, Hilary a. Smith
Ben Cao Gang Mu—Li Shizhen
Bacterio- therapy using fecal flora: toying with human motions—United Nations Educational, Scientific and Cultural Organization

References

[1] Baumgart DC and Sandborn WJ. (2012). Crohn's disease. The Lancet. 380 (9853): 1590–605.


[2] Borody TJ, Khoruts A. Fecal microbiota trans-plantation and emerging applications. Nat Rev Gastroenterol Hepatol 2011;9:88–96.


[3] Colman RJ and Rubin DT (2014). Fecal Microbiota Transplantation as Therapy for Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. Journal of Crohn’s & Colitis, 8(12), 1569–1581.

[4] Cui B, Feng Q, Wang H, Wang M, Peng Z, Li P, Huang G, Liu Z, Wu P, Fan Z, Ji G, Wang X, Wu K, Fan D, Zhang F (2015). Fecal microbiota transplantation through mid-gut for refractory Crohn's disease: safety, feasibility, and efficacy trial results. J Gastroenterol Hepatol. 30(1):51-8.

[5] Fong SC (2015). Distinct management issues with Crohn's disease of the small intestine. Current opinion in gastroenterology, 31(2), 92-97.

[6] Zhang F., Luo W., Shi Y, Fan Z, Ji G (2012) Should we standardize the 1,700-year-old fecal microbiota transplantation? Am J Gastroenterol.;107:1755; author reply p.1755-p.1756.

[7] FM, Wang HG, Wang M, Cui BT, Fan ZN, Ji GZ (2013). Fecal microbiota transplantation for severe enterocolonic fistulizing Crohn's disease. World J Gastroenterol, 19(41):7213-6.

Edited by Phuongngan Bui, a student of Nora Sullivan in BIOL168L (Microbiology) in The Keck Science Department of the Claremont Colleges Spring 2014.