Fecal Microbiota Transplantation for Gastrointestinal Disorders

Thomas Malikowski; Sahil Khanna; Darrell S. Pardi

Disclosures

Curr Opin Gastroenterol. 2017;33(1):8-13. 

In This Article

Abstract and Introduction

Abstract

Purpose of review The importance of the gut microbiome in human health is being increasingly recognized. The purpose of this review is to examine the existing literature pertaining to alterations in the gut microbiome and the utility of microbiome restoration therapies in gastrointestinal disorders.

Recent findings Imbalance and maladaptation of the microbiome, termed dysbiosis, has been associated with several disease states such as irritable bowel syndrome, Clostridium difficile infection, inflammatory bowel diseases, nonalcoholic fatty liver disease, and obesity among others. The possibility of restoration of normal microbiota has become an attractive concept for diseases in which the normal microbiome is perturbed. The rationale of using fecal microbiota transplantation to treat disease has been validated by its successful use in treating recurrent Clostridium difficile infection, which occurs as a result of decreased microbial diversity in the gut, most often in the setting of recent antibiotic treatment. Similar strategies may be applicable to other disorders.

Summary Alterations in the gut microbiome are associated with several disorders, and microbiome restoration based therapies such as fecal microbiota transplantation may be an adjunct to conventional treatments but more investigation is needed.

Introduction

The human microbiome consists of all the living microorganisms in the human body along with their associated genetic material. Within the last decade, the role that the microbiome plays in human health has become a topic of increasing interest. Although the microbiome is present in many parts of the human body, the gut contains the majority of microbial life. In fact, there are trillions of microbes in the gut, outnumbering the amount of cells in the entire human body ten to one.[1] The microbiome is incredibly diverse, containing thousands of species of bacteria, fungi, and viruses, with many species having never been successfully cultured in vivo. The composition of the microbiome is also variable, with differing species predominating in various local environments between the oral cavity and the distal colon.[2,3] The microbiome is also dynamic, and can change rapidly. The composition and proportions of microbial factions is impacted by many factors including dietary modifications, social behavior, aging, genetic and environmental factors.[3–7]

The most common bacteria found in the gut consist of four main phyla: Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria.[8] Although the ideal composition of the healthy microbiome has yet to be defined, it has been proposed that the overall function of the microbiome and its resulting host interactions may be more important than the specific microbial composition itself. Furthermore, the ability of the microbiome to resist and recover from stress is valued as an essential factor in maintaining a healthy microbiome.[2]

For years, the microbiome was thought to play a minimal role in human health, and the study of it was neither practical nor was it felt to be useful. Advances in technology have made the enormous task of investigating the microbiome far more efficient, practical, and cost effective. Rapid DNA sequencing and bioinformatics have exponentially improved the ability to decode this vastly complicated frontier.[8,9]

Due to its complex composition and function, the microbiome is regarded by many authors as a 'virtual organ.' The microbiome has an intimate relationship with human physiology, with microorganisms interacting with human cells in numerous ways. At the level of the gut mucosa, microorganisms interact with both the intestinal epithelium and with immune cells, playing an important role in the development and maintenance of mucosal immunity and gut permeability. The intestinal microbiome stimulates the production of IgA immunoglobulin and antimicrobial peptides by the mucosal immune system, and is linked to T-cell differentiation.[10] In addition, the gut microbiome produces a variety of physiologically active substances through fermentation and microbial processing of food constituents that have a variety of effects on the host.

For example, bacteria participate in the breakdown of polysaccharides into short chain fatty acids (SCFAs) such as butyrate, acetate, and propionate. These SCFAs impact local gut inflammation, vascular resistance, motility, and gene expression while acting as an energy source to intestinal epithelial cells. In addition, SCFAs are absorbed systemically, acting as substrates in the liver and peripheral tissues for lipogenesis and gluconeogenesis. The constituents of microbes themselves also have physiologic impact. Lipopolysaccharide and peptidoglycan, structural components of bacteria, can lead to local inflammation, affecting gut permeability. Thus, the microbiome interacts with the host through a variety of mechanisms, most importantly through association with the mucosal immune system and through release of physiologically active substances.[10–12]

Imbalance and maladaptation of the microbiome can occur, contributing to certain disease states. This is referred to as dysbiosis, and has been associated with gastrointestinal disorders including C. difficile infection, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease and slow transit constipation (STC).[1,8,13–15] In addition, alteration in the microbiome has been associated with nongastrointestinal disorders including obesity and metabolic syndrome, neuropsychiatric disorders, multiple sclerosis, atherosclerotic cardiovascular disease, autism, fibromyalgia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura.[14,16,17]

Although an association between dysbiosis and disease has been established, it remains unclear whether or not dysbiosis leads to disease or is merely a manifestation of disease. However, it is conceivable that manipulation of the microbiome could be a therapeutic strategy for various disease states. Prebiotics (substances to encourage microbial growth), probiotics (live microbial cultures), and synbiotics (combinations of prebiotics and probiotics) have been studied in a broad spectrum of disorders although to date they have generally been limited in effectiveness. A potential hypothesis for this shortcoming is that these agents lack the microbiological diversity represented in the healthy human gut. As stool naturally contains the entire gut microbiome, fecal microbiota transplantation (FMT) has gained appeal as a therapeutic option.

The rationale of using FMT to treat disease has been validated by its successful use in treating recurrent C. difficile infection, which occurs as a result of decreased microbial diversity in the gut, most often in the setting of recent antibiotic treatment. Studies have shown significant benefit in restoring microbial diversity through FMT, with a large majority of patients achieving complete cure of infection.[18–21]

FMT is performed using an infusion of liquid feces from a healthy donor into the gut of a recipient. It can be administered a number of ways including via nasoenteric tube, upper endoscopy, enema, and colonoscopy.[22] When performed properly, FMT is relatively safe with few serious adverse effects.[23] Abdominal discomfort or functional abdominal symptoms following FMT are the most common side-effects, while serious adverse effects such as death and infection are rare.[23]

This review will focus on the applications of FMT for gastrointestinal disorders other than C. difficile infection, including an examination of the existing literature on IBS, inflammatory bowel syndrome, NAFLD, and alcoholic liver disease.

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