Microbiome possibly a rich source of new drugs

antibiotic inhibiting growth of S. Aureus.

There has been a bit of popular press recently about an article published in Cell by a group of scientists at UCSF.  The research team that published this article had previously developed an algorithm to look at microbial genetic data and identify genes that were coding for natural products (small molecules that have some, usually unknown, purpose).  Natural products are generally produced in low amounts, or only produced under certain conditions, so they are difficult to discover and isolate.  Throughout pharmaceutical industry history, natural products have been a great source for antibiotic and other pharmaceutical development, because several of their functions mediate microbe to microbe interactions.

When the researchers tested the microbiome genes in the Human Microbiome Project's database using this algorithm, they discovered tens of thousands of new, natural products, including over 3000 that are found in the average individual's microbiome.  Of these 3000 they even found a vaginal microbe from a bacteria, Lactobacillus gasseri, that created a molecule that was similar to an antibiotic that is currently in clinical trials.  When the molecule's antibiotic efficacy was tested in the laboratory, the scientists discovered that it was a potent antibiotic towards common gram-positive pathogens.

The microbiome is an extraordinarily complex system which is one of the primary reasons it has taken so long to properly investigate.  This complexity however, could lead to a gold mine of new compounds and molecules to discover, especially in a system where competition, cooperation, and communication between bugs is so high.  Based on this research, I don't think it will be long before a molecule originally discovered in the microbiome is commercialized.

The human microbiome project, part 2. iHMP blog #1

The human microbiome project (HMP) was a large scale program sponsored by the NIH's common fund, which sought to define the healthy human microbiome.  The HMP was a success, and its main findings serve as a foundation upon which most microbiome science is built (cited almost 700 times in 2 years!). Perhaps it was the unexpected successor to the human genome project (HGP), but it is already nearing the HGP in influence.  

Because of its success the NIH is sponsoring the human microbiome project 2 (HMP2), otherwise known as the integrative human microbiome project (iHMP).  Where HMP1 investigated what the human microbiome looked like, iHMP is looking at how the human microbiome is associated with various "exemplars of microbiome-associated human conditions".  

These three conditions are:

1) "Pregnancy, including those that end in preterm birth"
2) "Gut disease onset, using inflammatory bowel disease (IBD) as a model"
3) "Respiratory viral infection and onset of type 2 diabetes (T2D)"

iHMP will track large cohorts of individuals for each of these conditions for 3 years to perform complete longitudinal studies.  Many variables and data sets will be tracked, compiled, and made public.  Of course bacteria will be sampled, but, for the first time, comprehensive sampling of metabolites from those bacteria will also be performed. The results of iHMP will be published periodically and will last from 2013 to 2016.

We would like to thank the entire HMP consortium of scientific investigators for their efforts, but especially Lita Proctor, who has championed the microbiome within the NIH for many years.  Her perspective on iHMP, which was recently published in Cell, was the basis for this blog post and from where the quotations are drawn.

We will will kick off a 3 part blog series here on the AMI blog where I review the 3 microbiome conditions that are being studied in the iHMP.  Check back on Monday for a post discussion about how the microbiome is associated with pregnancy, and how the iHMP plans to perform its investigation.