Enhancing the probiotic beneficial potential of the genus Lactobacillus.

BackgroundThe bacterial genus Lactobacillus has historically been the source of many strains with supposed but also proven health benefits. The selection of strains with potential health benefits has always been performed on a rather ad hoc basis based on knowledge on the isolation source of the strain and on expensive and labor-intensive lab screenings. Now that we are able to sequence whole genomes of many bacterial strains relatively cheaply it has become possible, in theory, to identify genomic signatures of strains with potential health benefits to be used for more informed, and more upscalable, screening. For some well-studied probiotic properties, the gene families encoding them have been identified and can therefore be used for probiotic screening. An example are the pili of the well-known probiotic strain Lactobacillus rhamnosus GG that are responsible for adhesion to the human colon epithelium. The gene cluster encoding these pili has been identified and the presence of this cluster can easily be identified in a given bacterial genome. Pili, as well as other potentially probiotic properties, can now already be used as screening criteria for potential probiotic strains. Systematic screening of genomes for these properties has only been performed in a limited way; the most comprehensive study to date included more than 200 species of Lactobacillus, but was limited to only one representative strain per species, while many of these genes are known to be very strain-specific and many more genomes are publicly available. A second way to improve genomic screening for probiotic potential is to systematically identify, on a large scale, genomic signatures associated with Lactobacillus strains engaging in symbiotic relations with Homo sapiens. These genomic signatures can be the presence of certain gene families, such as the gene cluster encoding the pili of LGG, but also gene copy numbers or even the presence of certain pieces of DNA gained from the environment, such as viral genomes or transposons, that betray the habitat of the strain. GoalsThe goal of this project is to enhance the potential of the genus Lactobacillus as a source of strains with potential health benefits. We aim to do this in two ways. First, we want to characterize already known gene families that encode probiotic properties by assessing their distribution across the more than 2000 Lactobacillus genomes that are publicly available. We will also assess their presence in the more than 100 genomes of strains isolated and sequenced by our own lab. Our second goal is to identify genomic signatures of symbiotic relations with humans as a species. Since we don't know on beforehand which strains are symbiotic for most of the publicly available genomes, we will perform this search in an unsupervised manner. To put it differently: we will look for sets of genomes that are not necessarily closely related, but underwent similar adaptations in their recent evolutionary history. We will look, in other words, for convergent evolution. If we succeed in finding groups of strains that underwent convergent evolution, we can assess whether already known probiotic strains are part of one or more of these groups. This would be a strong indication that other strains within these groups will also show probiotic potential.

Keywords:GENOTYPE-PHENOTYPE CORRELATION

Disciplines:Microbiomes