Analyzing the Human Microbiome: A "How To" Guide for Physicians

Andrea D Tyler, PhD; Michelle I Smith, PhD; Mark S Silverberg, MD; PhD

Disclosures

Am J Gastroenterol. 2014;109(7):983-993. 

In This Article

Abstract and Introduction

Abstract

The application of high-throughput next-generation sequencing to the analysis of the human microbiome has led to a shift in our understanding of the etiology of complex diseases. In consequence, a great deal of literature can now be found exploring this complex system, and reviewing recent findings. Observations of alterations in the intestinal microbiome associating with inflammatory bowel disease and other chronic conditions are well supported and have been widely accepted by the research community. Yet, it can be difficult to objectively evaluate the importance of these results, given the wide variety of methodologies applied by different groups in the field. The aim of this review is to focus attention on the basic principles involved in microbiome analyses, and to describe factors that may have an impact on the accurate interpretation of results.

Introduction

Over the past several years, a great deal of study has been directed toward evaluating the microbes living in or on the human host—the human microbiome. The human microbiome is defined as the collection of organisms and their genomes, inhabiting different anatomical locations both in and on humans.[1] The gut alone is home to hundreds of trillions of microorganisms and contains more genetic information than that which exists in the human genome.[2] Changes in human-associated microbial communities have been implicated in the etiology and increased incidence of several chronic conditions including obesity, diabetes, and inflammatory bowel disease (IBD).[3–7] Evidence for a role of these microbes in the etiology of IBD is quite well supported, and it has been reviewed elsewhere.[8–10] The intestinal flora has also been implicated in the development of the immune system, being shown in several studies to have an important role in immune development.[11,12] It has been argued that the increasingly "clean" environments typical of developed countries have contributed to reduced exposure of the immune system to microbes and infection and a subsequent increased prevalence of autoimmune conditions.[13] This so-called "hygiene hypothesis" suggests that exposure to fewer bacteria, viruses, or eukaryotic parasites prevents the immune system from developing properly during childhood and adolescence, leading to dysregulation and disease. Thus, improvements in sanitation, increased use of antibiotics, and reduced exposure to pathogens, although exceedingly successful in improving public health, may have had unforeseen consequences on the function of the immune system. Evidence regarding the role of any single pathogenic organism in preventing or causing autoimmune disease is lacking, suggesting instead that "cleaner" environments may alter human microbial community composition as a whole, in turn preventing the development of host immune tolerance and homeostasis.

Perhaps surprisingly, bacteria exist only rarely in isolation, and are instead most commonly found in complex community assemblages in which numerous different organisms share a similar ecological niche.[14,15] In many cases, these organisms are co-dependent on one another, requiring metabolic support from additional members of the community for survival.[16] In addition, organisms residing in or upon higher-order taxa must maintain a delicate balance with the host, in order to ensure that both symbionts flourish.[17] In most cases, the relationship between such organisms is mutually beneficial: gut microbes, for example, help with the digestion of nutrients, prevent colonization of the host by pathogenic organisms, and aid in the proper development of both the intestinal epithelium and immune system, while the host provides nutrients and a suitable habitat for bacterial growth.[18] The importance of this relationship and its subsequent consequences for human health is only beginning to be understood, and it has resulted in a great deal of study being directed in this field.

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