Principles of DNA-Based Gut Microbiota Assessment and Therapeutic Efficacy of Fecal Microbiota Transplantation in Gastrointestinal Diseases

Abstract

Fecal microbiota transplantation (FMT), a process by which the normal gastrointestinal microbiota is restored, has demonstrated extraordinary cure rates for Clostridium difficile infection and low recurrence. The community of microorganisms within the human gut (or microbiota) is critical to health status and functions; therefore, together with the rise of FMT, the gastrointestinal microbiota has emerged as a ‘virtual' organ with a level of complexity comparable to that of any other organ system and capable to compete with powerful known antibiotics for the treatment of several disorders. Although treatment protocols, donor selection, stool preparation and delivery methods varied widely, with a few reports following an identical protocol, FMT has diffused to other areas where the alterations of the gut microbiota ecology (or dysbiosis) have been theorized to play a causative role, including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), among several other extra-intestinal disorders (i.e. metabolic syndrome and obesity, multiple sclerosis, cardiovascular diseases). FMT can be relatively simple to perform, but a number of challenges need to be overcome before this procedure is widely accepted in clinical practice, and currently, there is no consensus between the various gastrointestinal organizations and societies regarding the FMT procedure. In this article, we describe the modern high-throughput sequencing techniques to characterize the composition of gut microbiota and the potential for therapeutics by manipulating microbiota with FMT in several gastrointestinal disorders (C. difficile-associated diarrhea, IBD and IBS), with a look on the potential future directions of FMT.

A double‐blind, placebo‐controlled study to assess the effect of a probiotic mixture on symptoms and inflammatory markers in women with diarrhea‐predominant IBS

“…There are several possible explanations for our negative result. Firstly, the same treatment was used for all participants, whereas the future of probiotic therapy may involve tailoring specific organisms to individual patients . In addition, IBS is a complex multifactorial syndrome with different pathogenic mechanisms operating in concert so a combination of therapies, rather than monotherapy, is more likely to be beneficial .…”

“…Firstly, the same treatment was used for all participants, whereas the future of probiotic therapy may involve tailoring specific organisms to individual patients. 43 In addition, IBS is a complex multifactorial syndrome with different pathogenic mechanisms operating in concert so a combination of therapies, rather than monotherapy, is more likely to be beneficial. 44 Another possible explanation could have been that despite the treatment, the probiotic microorganisms did not have an increased concentration in the intestines.…”

Fecal microbiota transplantation is a rescue treatment modality for refractory ulcerative colitis

“…[11] Therefore, the attention of clinicians has been focus on detecting remarkable changes using these advanced techniques in the gut microbiota of patients with UC. The role of each species of intestinal microbiota is not known exactly yet.…”

In search of stool donors: a multicenter study of prior knowledge, perceptions, motivators, and deterrents among potential donors for fecal microbiota transplantation

“…2,8 Fecal microbiota transplantation (FMT) is a highly effective therapy for patients with recurrent C. difficile infection, with a greater than 90% success rate. [9][10][11][12] Emerging evidence suggests that FMT may also have therapeutic benefits in other conditions associated with perturbed gut microbiota, including ulcerative colitis, [13][14][15][16] Crohn's disease, 17 irritable bowel syndrome, 18 metabolic syndrome, 19,20 multiple sclerosis, 21,22 depression, 23 and autism. 24,25 Intense interest in FMT is evident, with over 250 clinical trials registered on of January 11, 2019.…”