The human body is colonized by thousands of microbial species, together referred to as the microbiome. Humans have about ten times more microbial cells than human cells, and the number of genes contained in the microbiome is more than 100 times greater than the number found in the human genome.
Microorganisms have traditionally been examined in laboratory cultures and most of the microbial species within the human body have never been successfully isolated, which is probably due to certain growth conditions of these species that are unavailable in laboratories. The influence that these microbial species have on the immunity, nutrition, development, and physiology of humans is therefore almost completely unknown.
Today, technological advances in DNA sequencing have led to the development of a new research area referred to as metagenomics, which enables the study of microbe species, without the need for laboratory culture. In metagenomics, genetic material is taken directly from communities of microbes as opposed to single bacterial strains being cultured in the laboratory and then reassembled in attempts to create communities.
The National Institutes of Health Human Microbiome Project (HMP) is an initiative that aims to combine this technology with the genetic analysis of known reference strains in order to characterize microbial communities at various sites in the body and draw parallels between changes that occur in the microbiome and changes in human health.
A number of other sophisticated ‘omics techniques such as proteomics, metabolomics, and transcriptomics are also being used to generate information about interactions between the microbiome and human host and how these are relevant to health and disease.
The HMP is part of an international collaboration that aims to produce detailed microbiome datasets and tools that can be made publicly available and used as a community resource by anyone trying to enhance understanding of human health.
The first phase of the project was centered around the generation of metagenomics data and computational methods that could enable characterization of the microbiome in both healthy people and individuals with specific diseases related to the microbiome. A program was also developed to address the issues surrounding the ethical, legal, and societal implications associated with research into this area. The next phase was focused on using various ‘omics technologies to generate sets of integrated information on the biological properties of the host and the microbiome.
To begin with, researchers have sequenced microbial communities from 18 different sites in the nose, skin, vagina, mouth, and gut using samples from 300 healthy adults. This is expected to provide an understanding of the microbes that are present when the body is in a healthy state. In addition, the microbiomes of patients with specific diseases are being sequenced, including the inflammatory bowel conditions Crohn’s disease and necrotizing enterocolitis (which is often fatal to babies that are born prematurely). Other areas being investigated include how the microbiome is associated with sexually transmitted infections and with acne.
Through examining how the differences in genetics between individual microbes, as well as between the different sites, researchers hope to learn more about the involvement of the microbiome in health and disease states, with the ultimate aim being to provide new diagnostic approaches and therapies to treat various diseases.
Reviewed by Susha Cheriyedath, MSc Further Reading