(via Scintilla)

The article on "Probiotics modulation of mammalian metabolism" published this week in Molecular Systems Biology by Jeremy Nicholson and colleagues (Martin at al, 2008) has attracted some attention (read the nice summary in Science News) in some (very) popular media (here, here, here and here).

In this follow-up study of the paper published last year (Martin et al, 2007), the team lead by Jeremy Nicholson, in collaboration with Nestlé, demonstrates clear physiological effects of oral probiotics administration on mice harbouring a humanized microbiome. The effects are intricate: both the host flora and metabolism are altered. By analyzing metabolite pools in several compartments (liver, blood, urine, feces, gut), and following in parallel the host microbiota, patterns of correlations between microbial species and metabolites start to be visible and reveal the probiotics-induced modulation of the microbial-mammalian interactions. But the actual paper is really just next door (synopsis), so have a look...

How will these results translate to humans? What will be the best way to influence our microbiome? Drugs or yoghurt? These are fascinating questions and the understanding of how our physiology depends on the microbial flora could have profound consequences, particularly in these times when we seem to be in a "rush to gene-based solutions to all our problems" (Wilson, 2007). Will personal genomics have to ultimately develop into personal metagenomics to include our "extended" microbial genome?

Even if I usually prefer to resist the temptation of a self-promoting section in this blog, I find the attention of the media for this topic interesting (despite the usual variable accuracy of newspaper reports) because it points to an area where systems biology provides insights into topics of immediate interest to the general public.

The NIH has recently started its Human Microbiome Project. In this context, this study also underscores the importance of developing model systems and tools to manipulate the microbiome and to analyze the incredibly dense and intricate interactions that connect host and microbial species. A field where top-down systems biology seems indeed a very pragmatic and promising approach.

(via Jonathan A. Eisen, The Tree of Life)
What are the areas that will deeply transform biomedical research over the next decade? One of the possible areas identified for inclusion in the NIH Roadmap is research on the Microbiome (the entire set of microbial species living in the human body). A string of recent studies have revealed a profound impact of the enormously complex mammalian microbiome (Gill et al, 2006) on the metabolism and immune status of the host (for a few examples: Backhed et al, 2004, Dumas et al, 2006, Turnbaugh et al, 2006, Kitano & Oda, 2006, Nicholson et al, 2005). In his blog, J Eisen reports on some of the discussions held at an NIH sponsored workshop on the necessity of a Human Microbiome Project and lists possible research avenues for such a program. From his post:

1. Sequence many "reference genomes." By reference genomes here I mean genomes of cultured isolates that are closely related to organisms known in various human locations.
2. Do metagenomic sequencing of a variety of human mirobiome samples.
3. Conduct large scale human microbiome diversity studies. This could involve rRNA PCR surveys as well as some amount of genome sequencing.
4. Develop the computational tools needed to analyze the massive amounts of data that will come out.
5. Encourage the development of new methods to aid in studies of the microbiome.

A friend of mine asked me recently what field might strike the popular consciousness in the coming years. Could it be that it will be the realization that we are all "superorganisms" (Lederberg, 2000) and that our health does not only depend on our personal genome (Church 2005) and our environment, but also on the extended genome provided by our very private microbiome?