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Background  An important trait of probiotics is their capability to reach their intestinal target sites alive to optimally exert their beneficial effects. Assessment of this trait in intestine-mimicking  in vitro  model systems has revealed differential survival of individual strains of a species. However, data on the  in situ  persistence characteristics of individual or mixtures of strains of the same species in the gastrointestinal tract of healthy human volunteers have not been reported to date.    Methodology/Principal Findings  The GI-tract survival of individual  L. plantarum  strains was determined using an intestine mimicking model system, revealing substantial inter-strain differences. The obtained data were correlated to genomic diversity of the strains using comparative genome hybridization (CGH) datasets, but this approach failed to discover specific genetic loci that explain the observed differences between the strains. Moreover, we developed a next-generation sequencing-based method that targets a variable intergenic region, and employed this method to assess the  in vivo  GI-tract persistence of different  L. plantarum  strains when administered in mixtures to healthy human volunteers. Remarkable consistency of the strain-specific persistence curves were observed between individual volunteers, which also correlated significantly with the GI-tract survival predicted on basis of the  in vitro  assay.    Conclusion  The survival of individual  L. plantarum  strains in the GI-tract could not be correlated to the absence or presence of specific genes compared to the reference strain  L. plantarum  WCFS1. Nevertheless,  in vivo  persistence analysis in the human GI-tract confirmed the strain-specific persistence, which appeared to be remarkably similar in different healthy volunteers. Moreover, the relative strain-specific persistence  in vivo  appeared to be accurately and significantly predicted by their relative survival in the intestine-mimicking  in vitro  assay, supporting the use of this assay for screening of strain-specific GI persistence.

Congruent Strain Specific Intestinal Persistence of Lactobacillus plantarum in an Intestine-Mimicking In Vitro System and in Human Volunteers