that while about 70 percent of the genome of L. plantarum is shared among all strains, there are many genes not shared by all strains and many strain-specific genes.

Strain individuality raises the key question: What is the correlation with functional diversity? Currently, Danone investigators have been exploring the “pangenome” of multiple strains of two species, L. rhamnosus and L. paracasei, for gene-function correlations. Researchers are building a genome diversity database and coupling that with an extensive phenotyping program. Such studies will help to identify both common activities shared by many strains and specific features that can only be delivered by a few strains.

According to van Hylckama Vlieg, Danone scientists are looking at phenotypes related to carbohydrate utilization and short-chain fatty acid production, antimicrobial activity, and immune modulation. As an example of the type of results they are collecting, a sequencing analysis of 12 strains of L. rhamnosus and 30 strains of L. paracasei indicated that about 30 to 40 percent of the genome is “core,” that is, shared among all strains. However, up to 25 percent of genes are strain-specific, with different strains having different immune function effects (i.e., based on an NF-kappa B-type screen on HT29 cells).

DISCUSSION

Most of the discussion during the question-and-answer period at the end of this session revolved around three major issues: (1) functional consequences of modulating the microbiome through food, (2) whether there are any known adverse effects of prebiotic and probiotic interventions, and (3) experimental design and study size.

Focus on Function

A recurring theme of the workshop was the importance of functional, not just compositional, changes to the microbiome as a result of dietary (or antibiotic) intervention. For example, as summarized in this chapter, Johan van Hylckama Vlieg mentioned research results demonstrating that Activia does not cause any major perturbation of the microbiota but does trigger distinct transcriptomic responses related to the metabolic activity of Bifidobacterium animalis. Also, George Fahey commented on the results of a study showing several positive metabolic outcomes associated with oligofructose consumption in mice. Finally, James Versalovic elaborated on the many ways that probiotics can impact host immunity. An audience member asked whether, given that food products appear to impact the microbiome not by recolonizing (so not by changing the taxonomic makeup of the mi-



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