In the past decade, the concept of the ‘microbiome’ has come to the forefront of biomedical research. In the human body, microorganisms out-number our own cells 10:1, and the notion that a person’s genetic make-up is not limited to human cells’ DNA, but also the DNA of every microbe residing within/on that individual has spurred hypotheses about how our individual microbiomes affect our physiology and function.
The microbiome is immensely diverse across different body sites, where each site is colonized by bacteria adapted to that particular environment. VIDD Associate Member David Fredricks, whose lab studies bacterial vaginosis (BV), serves as VIDD’s unofficial authority on the human microbiome.
“It is a desert versus rainforest,” Fredricks said as he described the vast difference between the skin and intestinal tract niches. “In fact,” he continued, “stool has the highest density of microbes of any known ecosystem on our planet.”
Five years ago, as part of the NIH’s roadmap, the Human Microbiome Project (HMP) was established; a consortium of scientists to sequence and characterize the human microbiome. A multitude of HMP studies have recently been published within the last 10 months that identified bacterial communities in healthy individuals, those associated with certain diseases, and the differences between communities at different body sites, to name a few. The HMP awarded Fredricks two grants to develop 1) novel computational tools for efficiently analyzing the enormity of data generated from these studies, and 2) innovative methods for propagating heretofore non-culturable organisms.
The Fredricks lab focuses on using these technologies to study BV. Unlike many other vaginal diseases such as chlamydia or gonorrhea, BV is defined symptomatically rather than by one specific bacterial species. Because few bacterial taxa can withstand the low vaginal pH (4.5), Lactobacillus species, which can tolerate high acidity, make up the majority of the normal microbiota. In fact, increased vaginal pH is one finding in BV and is associated with a reduction of lactobacilli and an overgrowth of various anaerobes, such as Gardnerella vaginalis, Atopobium vaginae, and Prevotella species, that can tolerate this less acidic environment.
Giving great consternation to scientists and clinicians, the etiology of BV remains unknown. Because BV is idiopathic, heterogeneous, and stochastic, many conventional methods are insufficient for identifying the concomitant risk factors and/or bacterial culprits responsible for disease onset.
One molecular method Fredricks utilizes to overcome this hurdle is high throughput sequencing of bacterial genomes at the 16S rRNA region, which has conserved regions in all bacteria but also contains unique genetic signatures that act as bacterial barcodes. This highly sensitive and efficient sequencing method can identify a plentitude of species from one vaginal swab and is therefore useful for experiments that seek to more completely characterize the composition of these complex microbial communities.
