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

Abstract

<div><h3>Background</h3><p>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 <em>in vitro</em> model systems has revealed differential survival of individual strains of a species. However, data on the <em>in situ</em> 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.</p> <h3>Methodology/Principal Findings</h3><p>The GI-tract survival of individual <em>L. plantarum</em> 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 <em>in vivo</em> GI-tract persistence of different <em>L. plantarum</em> 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 <em>in vitro</em> assay.</p> <h3>Conclusion</h3><p>The survival of individual <em>L. plantarum</em> strains in the GI-tract could not be correlated to the absence or presence of specific genes compared to the reference strain <em>L. plantarum</em> WCFS1. Nevertheless, <em>in vivo</em> 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 <em>in vivo</em> appeared to be accurately and significantly predicted by their relative survival in the intestine-mimicking <em>in vitro</em> assay, supporting the use of this assay for screening of strain-specific GI persistence.</p> </div