Fecal microbiota transplantation in gastrointestinal disease: 2015 update and the road ahead

Abstract

At its height, the Clostridium difficile infection epidemic caused approximately 7000 infections and 300 deaths per day in the USA. Fecal microbiota transplantation (FMT) has demonstrated extraordinary clinical resolution, C. difficile infection cure rates of over 90%, and low recurrence. In tandem with the rise of FMT, the gastrointestinal microbiome has emerged as a ‘vital’ organ armed with a wealth of microbe ‘soldiers’ more powerful than known antibiotics. FMTs’ reputation has diffused into many new ‘indications’ yet these appear to be merely the tip of the iceberg when considering its potential applications. FMT as a therapeutic tool has evolved from the original format of blended donor stool and moved towards a refined product comprising a myriad of microbial components, presented aesthetically as encapsulated lyophilized powder.

Keywords:

• antibiotic resistance
• fecal microbiota transplantation
• FMT
• FSM
• full spectrum microbiota
• microbiome
• probiotics

Financial & competing interests disclosure

T Borody has filed patents in the field of FMT and offers this treatment at the Centre for Digestive Diseases, Australia. He is also an unpaid consultant to Crestovo LLC. S Mitchell is an employee of the Centre for Digestive Diseases (New South Wales, Australia) where fecal microbiota transplant is offered as a treatment, and an employee of Crestovo LLC. M Fischer is an unpaid consultant to Crestovo LLC, OpenBiome and Rebiotix. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Fecal microbiota transplantation (FMT) has reached routine clinical use in relapsing Clostridium difficile infection (CDI) and is expanding its influence to incorporate other clinical indications.

• FMT employment in more severe forms of CDI and in inflammatory bowel disease (IBD) are not well-documented

• FMT use falls broadly into: specific microbiome infections, for example, vancomycin-resistant Enterococcus or CDI and ‘no detectable infection’ syndromes, for example, IBD or irritable bowel syndrome.

• Trial protocols for indications outside CDI demand a non-CDI design lest more ‘failed’ trials are reported.

• Clinical trial design for use of FMT in indications with ‘no detectable infection’ as in IBD should focus on testing variables that may improve remission, for example, comparing the donor microbiomes as a factor influencing remission.

• The evolving FMT products fall into two groups: stool-derived microbiota and synthetic microbiota, each with a range of advantages and disadvantages, including documented safety, disease efficacy, availability and processing/development costs, public opinion/acceptance.

• The safety and efficacy of FMT products are constantly being improved.

• FMT products will progressively become more utilized as accepted biologics prescribed for specific indications.