[From the archives; originally posted November 16, 2005]
I know, everyone’s so sick of all the new “omics”es. But “metagenomics” is one that I don’t see going away anytime soon. At its core, metagenomics is a way of looking at organisms in concert as a complex ecology, rather than as an individual, as genomic analysis has traditionally been done. Rather than isolating 10 different species of bacteria from, say, a gram of soil and analyzing them all separately, a metagenomics strategy would investigate all the organisms in the soil (or in sea water, dental plaque, or even human feces). A huge advantage to this approach is that we can get sequence data even from organisms that we’re unable to culture; as such, it’s not surprising that huge numbers of novel microbes are found whenever researchers tackle a new area using this strategy. Also, as you may expect, one focus of this research in humans is to discover causes and/or cofactors of diseases.
One of these diseases is bacterial vaginosis, one of the most common infections among women. Despite this distinction, scientists and doctors know little about the causes of bacterial vaginosis (BV), a usually benign disease that is also linked to serious health problems including pelvic inflammatory disease, an increase in the viral load of HIV from infected women and a two-fold increase in risk for pre-term labor and delivery. A study in the Nov. 3rd issue of the New England Journal of Medicine seeks to shed some light on this mystery.
Previous studies of this disease have been based on culture of bacterial organisms. However, this has a fatal flaw: we know that many of the bacteria that live within our bodies are not amenable to culture by traditional means. Therefore, investigators used a strategy targeting the bacterial 16sRNA gene. This is a gene present in all bacterial species that has been widely used for species identification. Their results?
Women without bacterial vaginosis had 1 to 6 vaginal bacterial species (phylotypes) in each sample (mean, 3.3), as detected by broad-range PCR of 16S rDNA, and lactobacillus species were the predominant bacteria noted (83 to 100 percent of clones). Women with bacterial vaginosis had greater bacterial diversity (P<0.001),>with 9 to 17 phylotypes (mean, 12.6) detected per sample and newly recognized species present in 32 to 89 percent of clones per sample library (mean, 58 percent). Thirty-five unique bacterial species were detected in the women with bacterial vaginosis, including several species with no close cultivated relatives. Bacterium-specific PCR assays showed that several bacteria that had not been previously described were highly prevalent in subjects with bacterial vaginosis but rare in healthy controls. FISH confirmed that newly recognized bacteria detected by PCR corresponded to specific bacterial morphotypes visible in vaginal fluid.
So, the women with BV not only had a greater diversity of bacteria, but they were also more likely to be colonized with these previously unknown species of bacteria. Obviously, if we don’t even have a clue as to what these bacteria are, we don’t know the best way to treat them. It still amazes me at times to contemplate how little we know about the organisms we are most intimately associated with.