In a healthy human adult, bacterial cells outnumber human cells, but the identity and degree of diversity of these bacteria in a single individual, their variability from person to person, and their role in disease and disease susceptibility has been largely unknown. The goal of the Human Microbiome Project is to characterize the human microbiome and analyze its role in human health and disease.
The human microbiome is defined as the collection of microbes - bacteria, viruses, and single-cell eukaryotes - that inhabits the human body. Microbes in a healthy human adult are estimated to outnumber human cells by a ratio of ten to one, and the total number of genes in the microbiome exceeds the number of genes in the human genome by a factor of at least 200. Even though microbial cells are only one-tenth to one-hundredth the size of a human cell, they may account for up to five pounds of adult body weight.
Although bacteria are often associated with infections, the bacteria that colonize the surface and insides of our bodies are essential for life. We are dependent on these bacteria to help digest our food, produce certain vitamins, regulate our immune system, and keep us healthy by protecting us against disease-causing bacteria.
The composition of the entire collection of microbes that make up the microbiome and its influence on our health and susceptibility to disease is not easily investigated. To date, only a small percentage of the bacteria that comprise the human microbiome have been identified, and a limited number of individual microorganisms have been studied. It simply has not been possible to isolate the vast majority (>95%) of microorganisms and culture them, presumably because the required growth conditions have not or cannot be reproduced in the laboratory. However, recent technological advances in DNA sequencing and the development of a method known as metagenomics have now made it feasible to analyze the entire human microbiome.
Metagenomics is a sequence-based approach that allows the genetic material from the complete collection of microbes to be analyzed without needing to cultivate the microorganisms. Microbial communities can be harvested from their natural environments, and their DNA sequences can be determined.
The metagenomic approach allows for the identification of microorganisms that were previously unrecognized and gives vastly more information than the analysis of singly isolated microbes. Researchers can determine the relative abundance of the different species and discover which metabolic pathways are encoded by the organisms to gain information about their functions in the body.
Importance of the Human Microbiome Project
The human microbiome makes up about one to two percent of the body mass of an adult. It has been likened to a body organ. But, unlike say a heart or a liver, the importance and function of the microbiome is just starting to be appreciated.
It has long been known that bacteria are involved in certain body processes, such as digesting food and producing vitamins, but the microbiome appears have a much broader impact on our health than was previously realized. The community of microbes in an individual may influence the susceptibility to certain infectious diseases, as well as contribute to disorders such as obesity and diabetes. It may also contribute to the development of some chronic illnesses of the gastrointestinal system such as Crohn's disease and irritable bowel syndrome. Some collections of microbes can determine how one responds to a particular drug treatment. The microbiome of the mother may even affect the health of her children.
A more complete understanding of the diversity of microbes that make up the human microbiome could lead to novel therapies. For example, it may be possible to treat a bacterial infection caused by a "bad" bacterial species by promoting the growth of the "good" bacteria. Microbiome transplants are already being used to combat certain illnesses, such as Clostridium difficile infections, to establish more healthful bacterial populations.
Alkek Center for Metagenomics and Microbiome Research
The Alkek Center for Metagenomics and Microbiome Research (CMMR) at Baylor, based in the Department of Molecular Virology and Microbiology, serves as an international hub for microbiome research including clinical and basic science applications and advanced bioinformatics analyses. The CMMR was established in 2011 and is directed by MVM faculty member Dr. Joseph F. Petrosino, a nationally recognized leader in metagenomic research. It was founded as an extension to Baylor's involvement in the Human Microbiome Project and is supported in part by a generous donation from the Albert and Margaret Alkek Foundation.
The CMMR builds on the microbiology and virology expertise in the department and collaborates with the Human Genome Sequencing Center, headed by Dr. Richard Gibbs, and the Texas Children's Microbiome Center for pediatric studies under the direction of Dr. James Versalovic.
CMMR researchers are developing molecular and informatics tools and resources to advance diverse clinical and basic research projects pertaining to the organisms that comprise the microbiome, the genetic makeup of these microbes, how these microorganisms interact with human cells and tissues during the course of life and their impact on health and disease. The CMMR provides metagenomic, informatics, model system and molecular biology support and guidance to other researchers and clinical collaborators engaging in these areas of study.
The research thus far has been focused on defining a "normal" microbiome. Once the microbiomes from healthy individuals are catalogued, investigators would like to understand the roles these microbes play in our lives and how these communities are impacted by various environmental and genetic factors such as age, geographic location, diet, and ethnicity. They will want to examine the microbiomes of people with various illnesses to determine how the microbiome is altered in different disease states.
The total microbial gene content, or "pan-genome", of about 800 human samples has already been determined and hundreds more are currently being analyzed. Genome sequencing of individual bacteria, viruses and small eukaryotes is continuing to populate the reference "catalog". In addition, studies are underway to examine the viruses and eukaryotes that contribute to the overall microbiome.
Many questions remain. Among them, researchers would like to know how a specific microbiome is established in an individual and how it may change over time, how the human host and microbe community interact, how a particular microbiome affects nutrition and how changes in diet can affect the microbiome, how the microbiome affects immunity and can cause disease, how the microbiome is affected by antibiotics and how the microbiome affects the response to various drugs, and how a microbiome can be altered to improve health.
It is hoped that this research will lead to the development of new treatments and diagnostics for a variety of genetic and infectious diseases.