Fecal Microbiota Transplantation as New Therapeutic Avenue for Human Diseases

Abstract

The human body is home to a variety of micro-organisms. Most of these microbial communities reside in the gut and are referred to as gut microbiota. Over the last decades, compelling evidence showed that a number of human pathologies are associated with microbiota dysbiosis, thereby suggesting that the reinstatement of physiological microflora balance and composition might ameliorate the clinical symptoms. Among possible microbiota-targeted interventions, pre/pro-biotics supplementations were shown to provide effective results, but the main limitation remains in the limited microbial species available as probiotics. Differently, fecal microbiota transplantation involves the transplantation of a solution of fecal matter from a donor into the intestinal tract of a recipient in order to directly change the recipient's gut microbial composition aiming to confer a health benefit. Firstly used in the 4th century in traditional Chinese medicine, nowadays, it has been exploited so far to treat recurrent Clostridioides difficile infections, but accumulating data coming from a number of clinical trials clearly indicate that fecal microbiota transplantation may also carry the therapeutic potential for a number of other conditions ranging from gastrointestinal to liver diseases, from cancer to inflammatory, infectious, autoimmune diseases and brain disorders, obesity, and metabolic syndrome. In this review, we will summarize the commonly used preparation and delivery methods, comprehensively review the evidence obtained in clinical trials in different human conditions and discuss the variability in the results and the pivotal importance of donor selection. The final aim is to stimulate discussion and open new therapeutic perspectives among experts in the use of fecal microbiota transplantation not only in Clostridioides difficile infection but as one of the first strategies to be used to ameliorate a number of human conditions.

Keywords: fecal microbiota transplantation; gut microbiome; neurological disorders.

Figure 1

Stools sample preparation for fecal microbiota transplantation. Fecal stools (100–150 g) dissolved in saline solution (NaCl, 0.9%) are homogenized and larger particles removed by filtration. The fresh fecal sample can be used within less than 6 h for FMT. Alternatively, the fresh fecal preparation is further processed with multiple steps of filtration, cry-protected in glycerol (10%), frozen, and kept at −80 °C for later use. The preparation of FMT capsules involves the addition of freeze-drying protectant glycerol (20%), centrifugation (400× g), the supernatant is discarded and it is centrifuged again at high speed (10,000× g); the sediment is incorporated into an enteric-soluble capsule and stored at −80 °C [35]. Alternatively, the material can be lyophilized (vacuum dried) to obtain fecal powder inserted in capsules, and stored at −80 °C for later use. If multiple steps of microfiltration, centrifugation, and suspension are carried out using an automatic system, it is referred to as washed microbiota preparation (WMP). WMP transfer via colonic transendoscopic enteral tubing (TET) is referred to as washed microbiota transplantation (WMT).

Figure 2

Delivery methods for fecal microbiota transplantation. The delivery methods are classified into upper gastrointestinal routes, including nasogastric/nasoduodenal/nasojejunal tubes and capsules, and lower gastrointestinal routes, including enema colonoscopy and colonic transendoscopic enteral tubing.

Figure 3

Fecal microbiota transplantation in human diseases. Schematic cartoon summarizing fecal microbiota transplantation-based clinical trials in the different human diseases. Refer to the text for details.