What is the current state-of-the-art of faecal microbiota transplantation?

faecal microbiota transplantationFaecal microbiota transplantation has been demonstrated to be a safe and highly effective therapeutic option for refractory C. difficile infection (CDI), and many studies have shown that it may possibly have applications in other illnesses such as inflammatory bowel disease (IBD) and in particular for ulcerative colitis (UC). According to a recent systematic review with meta-analysis including observational studies, during the long-term follow-up (equal to or more than 90 days), FMT therapy was considered a highly effective and robust therapy for recurrent CDI.

 

FMT can be defined as the administration of a faecal solution from a donor into the intestinal tract of a recipient. The faecal material can be infused via a nasogastroduodenal tube or through performing a colonoscopy. Indeed, the route of FMT delivery may affect clinical outcome. A recent research study from individual patient data found that FMT delivered via the lower gastrointestinal route seems to be most effective for the prevention of recurrent/relapsing CDI.

 

On the whole, several considerations need to be taken into account for clinical practice. Donor screening and selection is crucial and the US Food and Drug Administration (FDA) suggests a single provider of frozen stool samples as a quality standard to be met. However, recent data presented at the 11th Congress of the European Crohn’s and Colitis Organisation, Inflammatory Bowel Diseases (ECCO-IBD) suggests the potential for multidonor pooled FMT to induce remission in patients with active UC.

 

The ultimate goal will be to provide a manufactured microbiota mixture in a standardized oral capsule that is “ready-to-use” for the patient. Such administration should include the standardization of the process and the approval by regulatory affairs.

 

Regarding the patient experience of undergoing FMT for recurrent C. difficile infection, a recent qualitative study reported that patients encountered multiple barriers to receiving FMT and the most relevant one was provider resistance/limited awareness about FMT as a treatment option. It was reported that there were also patients that had no concerns about any aspects of FMT. Patient activation behaviours -defined as the ability to self-manage health and healthcare (empowerment, information seeking, and having confidence to talk about treatment with providers)-were evident in the pre-FMT period, in the tipping point of hopelessness and frustration before FMT receipt, during FMT, and in the post-FMT period.

 

When conducting FMT in children, special considerations are needed as they have a dynamic and particularly vulnerable developing microbiome compared to adults. Paediatric studies have observed that FMT may be effective for recurrent CDI and in the short term in IBD. More randomized controlled trials (RCTs) are needed with long term follow up of FMT in children in order to provide evidence to support its efficacy and safety.

 

Given the success of FMT in CDI and UC, there has been a growing interest in FMT to restore microbiota diversity in other health conditions. This interest can be explained in part by the increasing prevalence of Clostridium difficile infection (CDI) and expanding association of intestinal dysbiosis with a wide range of diseases, including gastrointestinal conditions such as inflammatory bowel diseases and irritable bowel syndrome (IBS), as well as metabolic disorders such as obesity and type 2 diabetes. FMT has been considered for other digestive and non-digestive disorders associated with disturbances of the gut microbiota, which include autoimmune diseases, metabolic disorders, cancer, and neurologic and psychiatric diseases. However, the main limitations are lack of prospective controlled trials and the risk for transferring not only pathogens but also transient or persistent phenotypes such as obesity in the recipient host.

 

In conclusion, FMT has emerged as a novel tool for manipulating the intestinal microbiota to treat recurrent CDI and promising results are also reported for UC. Well-designed RCTs are needed to establish its efficacy and safety for other diseases that might allow improving human health via the reconstitution of intestinal microbiota diversity.   

References:

Furuya-Kanamori L, Doi SA, Paterson DL, et al. Upper versus lower gastrointestinal delivery for transplantation of fecal microbiota in recurrent or refractory Clostridium difficile infection: a collaborative analysis of individual patient data from 14 studies. J Clin Gastroenterol. 2016. doi:10.1097/MCG.0000000000000511.

 

Hourigan SK, Oliva-Hemker M. Fecal microbiota transplantation in children: a brief review. Pediatr Res. 2016. doi:10.1038/pr.2016.48.

 

Li YT, Cai HF, Wang ZH, Xu J, Fang JY. Systematic review with meta-analysis: long-term outcomes of faecal microbiota transplantation for Clostridium difficile infection. Aliment Pharmacol Ther. 2016;43(4):445-57.

 

Mattner J, Schmidt F, Siegmund B. Faecal microbiota transplantation-A clinical view. Int J Med Microbiol. 2016. doi:10.1016/j.ijmm.2016.02.003.

 

Pakyz AL, Moczygemba LR, VanderWielen LM, Edmond MB. Fecal microbiota transplantation for recurrent Clostridium difficile infection: The patient experience. Am J Infect Control. 2016. doi:10.1016/j.ajic.2016.01.018.

 

Smits LP, Bouter KE, de Vos WM, Borody TJ, Nieuwdorp M. Therapeutic potential of fecal microbiota transplantation. Gastroenterology. 2013;145(5):946-53.

 

Andreu Prados
Andreu Prados
Andreu Prados holds a Bachelor of Science Degree in Pharmacy & Human Nutrition and Dietetics. Science writer specialised in gut microbiota and probiotics, working also as lecturer and consultant in nutrition and healthcare. Follow Andreu on Twitter @andreuprados