Harvesting the microbiota: Faecal Microbiota Transplant

By Kai Yee Eng

Our gut is colonized by a group of microorganisms, forming a diverse ecosystem unseen by the naked eye. This colony includes archaea, bacteria, and virus, and they interact with the host in the gut environment, playing a huge role in managing the health of the host.1,2 These tiny organisms bring great impact by involving in key activities such as metabolism, immunity and even in brain functions. With this, it is clear that the gut microbiota plays a significant role in the human body. Therefore, if we could maintain a “normal” population of microbiota, it would provide great advantage to the human body. However, this may not always be the case. The question now would be how to revert the dysbiosis, the imbalance of the microbial community. Of all the current approaches in the medical field, it is believed that faecal microbiota transplant is the most effective of all.2
 
Faecal microbiota transplant, also recognized as faecal bacteriotherapy, refers to the transfer of microbiota from the stool sample collected from a donor to the patient. First, the donor is screened. Samples are screened to check for any presence of pathogens, or infections. Recently, it is reported that SARS-CoV-2 RNA can be found in stool samples.3 Therefore, this screening is utmost important. On the other hand, there are no standard guidelines for screening of recipient. However, it is suggested that the recipient should not be immunocompromised, to reduce potential risk of infections due to the delivery or other side effects.4 This stool sample is later screened again to inspect for any visible abnormalities. Then, the sample is mixed in a glycerol-saline solution and filtered.4 The filtered samples will later be processed according to the concentration required for the method of delivery. Faecal microbial transplant can be done via colonoscopy, sigmoidoscopy, enema, esophagogastroduodenoscopy, via nasoenteric tube or orally via capsule stool samples specifically designed to prevent bacteria degradation by stomach acid.5

The first faecal microbiota transplant was recorded in the 4th century, by a Chinese doctor named Ge Hong.1,6 It was done via oral method, to treat diarrhoea and food poisoning. In the 16th century, Li ShiZhen, the author of Compendium of Materia and Medica,7 had also described the use of faecal sample as a form of medication to treat severe diarrhoea, constipation and vomiting.6 The western medicine first formally recorded the use of faecal microbiota transplant in the 17th century in veterinary medicine.  It is coined the term “transfaunation”.8 In 1891, Bourke has published his records on a Belgium painter, feeding on his faeces for 23 days and other cases, feeding on pigeon and mouse dumping.9 Although this is not the common diet accepted by the public, World War II soldiers in Africa had confirmed the consumption of fresh camel faeces to help bacterial dysentery, a gastrointestinal infection which commonly associated with painful cramps and diarrhoea with blood and/or mucus.9 With this, it is no surprise that faecal microbiota transplant emerged as a therapeutic strategy in the modern medicine. 

Faecal microbiota transplant is most commonly applied in recurrent Clostridium difficile infection (RCDI), in which the conventional antibiotics treatment such as vancomycin shown no effect.1,2,10,11 In the report by Public Health England, from April 2017 to March 2018, there were 13,286 cases reported in England by NHS trust.12 After the first treatment, it is postulated that 20-30% of patients experience relapse infections, which is approximately 3000 to 4000 patients.13 Clostridium difficile in the gut microenvironment disrupt the balance of gut microbial community and populates in the gut. As the microbiota presence in gut is responsible for metabolism, specifically in secondary bile acid formation, which is related to the expansion of Clostridium difficle,14 the dysbiosis forms a positive loop cycle. The situation is further worsen when the antibiotic fails to reduce the amount of Clostridium difficile back to a healthy level while it acts on other “healthy” microbiota in the gut, providing a more optimum environment for the flourishing of Clostridium difficle. Faecal microbiota transplant comes in to introduce the “healthy” microbiota and compete with the Clostridium difficle for space and nutrient, as well as balancing the metabolism, increasing the secondary bile acid formation to reduce the growth of Clostridium difficle.  

While faecal microbiota transplant has been shown to be successfully restore the microbial community, there is a lack of long-term evidence and studies to show the possible consequences or side effects of this therapy. Dated till 2019, no major adverse effects or death has been reported directly due to the faecal microbiota transplant.15 However, as faecal samples are labelled as biologically active samples, more studies are required to understand the safety of this therapy.   

As stated above, this method is currently only administrated in recurrent Clostridile difficile infection patients, where antibiotics treatment has been shown to fail. Nevertheless, there are a lot more to learn about this method and how could we harvest the microbiota to confer the healthy benefits, in other medical complications such as obesity, inflammatory bowel diseases and Crohn’s disease, which the patients are reported to have a shift in gut microbiota composition compared to healthy person. Gut microbiota is also related to other functions, for example its role in the gut-brain axis, which is found to relate to autism and anxiety.16 With more research and studies, faecal microbiota transplant could be a possible therapeutic strategy to more gut microbiota-related diseases.  

References:

1.          Gupta S, Allen-Vercoe E, Petrof EO. Fecal microbiota transplantation: in perspective. Therap Adv Gastroenterol [Internet]. 2016 Mar 1 [cited 2021 Dec 14];9(2):229. Available from: /pmc/articles/PMC4749851/

2.            Borody TJ, Khoruts A. Fecal microbiota transplantation and emerging applications. Nat Rev

Gastroenterol Hepatol 2011 92 [Internet]. 2011 Dec 20 [cited 2021 Dec 14];9(2):88–96. Available from: https://www.nature.com/articles/nrgastro.2011.244

3.            Parvathy SN, Lenehan JG, Fernandes R, Poutanen SM, Hota S, Maleki Vareki S, et al. Enhanced donor screening for faecal microbial transplantation during COVID-19. Gut [Internet]. 2021 Nov 1 [cited 2021 Dec 13];70(11):2219–20. Available from: https://gut.bmj.com/content/70/11/2219

4.            Vindigni SM, Surawicz CM. Fecal Microbiota Transplantation. Gastroenterol Clin [Internet]. 2017 Mar 1 [cited 2021 Dec 12];46(1):171–85. Available from: http://www.gastro.theclinics.com/article/S0889855316300905/fulltext

5.            Chen J, Zaman A, Ramakrishna B, Olesen SW. Stool Banking for Fecal Microbiota Transplantation: Methods and Operations at a Large Stool Bank. Front Cell Infect Microbiol. 2021 Apr 15;11:281. 

6.            Zhang F, Luo W, Shi Y, Fan Z, Ji G. Should we standardize the 1,700-year-old fecal microbiota transplantation. Am J Gastroenterol. 2012 Nov;107(11):1755. 

7.            伟大医药学家李时珍和《本草纲目》–《自然杂志》1983年12期 [Internet]. [cited 2021 Dec 14]. Available from: https://www.cnki.com.cn/Article/CJFDTotal-ZRZZ198312018.htm

8.            Borody TJ, Warren EF, Leis SM, Surace R, Ashman O, Siarakas S. Bacteriotherapy using fecal flora: Toying with human motions. J Clin Gastroenterol [Internet]. 2004 Jul [cited 2021 Dec 14];38(6):475–83. Available from: https://journals.lww.com/jcge/Fulltext/2004/07000/Bacteriotherapy_Using_Fecal_Flora__Toying_With.3.aspx

9.            Lewin RA. More on Merde. Perspect Biol Med [Internet]. 2001 [cited 2021 Dec 14];44(4):594–607. Available from: http://muse.jhu.edu/journals/perspectives_in_biology_and_medicine/v044/44.4lewin.html

10.          Aroniadis OC, Brandt LJ. Fecal microbiota transplantation: Past, present and future. Curr Opin Gastroenterol [Internet]. 2013 Jan [cited 2021 Dec 14];29(1):79–84. Available from: https://journals.lww.com/co-gastroenterology/Fulltext/2013/01000/Fecal_microbiota_transplantation__past,_present.14.aspx

11.          FMT: Faecal microbiota transplantation | Guy’s and St Thomas’ NHS Foundation Trust [Internet]. [cited 2021 Dec 12]. Available from: https://www.guysandstthomas.nhs.uk/resources/patient-information/endoscopy/faecal-microbiota-transplantation-FMT.aspx

12.          Simon Thelwall ON, Jeremy Anselmo RH. Clostridium difficile infection: mandatory surveillance 2017/18 Summary of the Mandatory Surveillance Annual Epidemiological Commentary 2017/18 [Internet]. Public Health England. 2018 [cited 2021 Dec 14]. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/724368/CDI_summary_2018.pdf

13.          Wilcox MH, Ahir H, Coia JE, Dodgson A, Hopkins S, Llewelyn MJ, et al. Impact of recurrent Clostridium difficile infection: hospitalization and patient quality of life. J Antimicrob Chemother [Internet]. 2017 Sep 1 [cited 2021 Dec 14];72(9):2647–56. Available from: https://academic.oup.com/jac/article/72/9/2647/3867671

14.          Pérez-Cobas AE, Artacho A, Ott SJ, Moya A, Gosalbes MJ, Latorre A. Structural and functional changes in the gut microbiota associated to Clostridium difficile infection. Front Microbiol. 2014;5(JULY):335. 

15.          Singh T, Bedi P, Bumrah K, Singh J, Rai M, Seelam S. Updates in Treatment of Recurrent Clostridium difficile Infection. J Clin Med Res [Internet]. 2019 [cited 2021 Dec 14];11(7):465. Available from: /pmc/articles/PMC6575119/

16.          Clapp M, Aurora N, Herrera L, Bhatia M, Wilen E, Wakefield S. Gut microbiota’s effect on mental health: The gut-brain axis. Clin Pract [Internet]. 2017 Sep 15 [cited 2021 Dec 14];7(4):131–6. Available from: /pmc/articles/PMC5641835/

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