Baseline Clinical Data Established for the Human Microbiome Project

A recent paper described a significant advance in the effort to establish a rigorous clinically defined base for the "Human Microbiome Project.”

The microbiome is the totality of microbes, their genetic elements (genomes), and environmental interactions in a particular environment. The term "microbiome" was coined by the Nobel Prize-winning geneticist Joshua Lederberg, who argued that microorganisms inhabiting the human body should be included as part of the human genome, because of their influence on human physiology. The human body contains over 10 times more microbial cells than human cells, although the entire microbiome only weighs about 200 grams.

Investigators at Baylor College of Medicine (Houston, TX, USA) are among many collaborators working on the Human Microbiome Project. They coauthored a study in the March 2013 issue of the FASEB Journal that described the establishment of rigorous clinically defined criteria for the study of the microbiome.

They first screened potential 18 to 40 year-old participants using exclusion criteria based on health history, including the presence of systemic diseases (e.g., hypertension, cancer, or immunodeficiency or autoimmune disorders), use of potential immunomodulators, and recent use of antibiotics or probiotics. Subsequent physical examinations excluded individuals based on body mass index (BMI), cutaneous lesions, and oral health. Ultimately, they screened 554 individuals to enroll 300 (149 men and 151 women, mean age 26 years. They obtained specimens from the oral cavity, nostrils, skin, gastrointestinal tract, and vagina (15 specimens from men and 18 from women). The study evaluated longitudinal changes in an individual's microbiome by sampling 279 participants twice and 100 individuals three times. This sampling strategy yielded 11,174 primary specimens, from which 12,479 DNA samples were submitted to four centers for metagenomic sequencing.

In metagenomic sequencing, DNA recovered directly from environmental samples in an untargeted manner is analyzed using shotgun Sanger sequencing or pyrosequencing to recover the sequences of the reads. To determine the phylogenetic identity of a sequence, it is compared to available full genomes. One drawback of this approach is that many members of microbial communities do not have a representative sequenced genome. Despite the fact that metagenomics is limited by the availability of reference sequences, one significant advantage of metagenomics is that metagenomics data can elucidate the functional potential of the community DNA. Targeted gene surveys cannot do this as they only reveal the phylogenetic relationship between the same genes from different organisms. Functional analysis is done by comparing the recovered sequences to databases of metagenomic annotations. The metabolic pathways that these genes are involved in can then be predicted.

"While historically pre- and probiotics have dominated the microbiome landscape, emerging data from numerous labs as to the impact of dietary interventions and antibiotic exposure will play formative roles in tailoring therapy," said first author Dr. Kjersti M. Aagaard, associate professor of obstetrics and gynecology at Baylor College of Medicine. "We may find that the answers to our most common and prevalent health and disease states lies not in manipulating the human genome, but rather, in utilizing subtle shifts in diet and components of the diet, efficacy trials in prophylactic or preventative antibiotic therapies, and care attention to the over prescription of steroids and antibiotics."

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Baylor College of Medicine