show Abstracthide AbstractPlant-based foods contain bioactive compounds such as polyphenols that resist digestion and potentially benefit the host through interactions with their gut microbiome. Based on previous observations, we hypothesized thatprobiotic Lactobacillus plantarum interact with cranberry polyphenols and dietary oligosaccharides to synergistically impact its physiology. In this study, L. plantarum ATCC BAA-793 was grown on dietary oligosaccharides including cranberry xyloglucans, fructooligosaccharides, and human milk oligosaccharidesin conjunction with proanthocyanidins (PACs) extracted from cranberry. As a result, L. plantarum exhibits a differential physiological response to cranberry PACs dependent on the carbohydrate source and polyphenol fraction introduced. Of two extracts evaluated, the PAC1 fraction increased growth regardless of oligosaccharide whereas PAC2 positively modulates growth during xyloglucan metabolism. Interestingly, PAC1 enables ATCC BAA-793 to utilize fructooligosaccharides efficiently as it is unable to ferment this substrate ordinarily. Relative to glucose, oligosaccharide metabolism increases the ratio of secreted acetic acid to lactic acid. The PAC2 fraction differentially increases this ratio during cranberry xyloglucan fermentation compared with PAC1. RNA-seq transcriptomics link expression of putative polyphenol degradation genes, polyphenol degradation profiles, and physiological phenotypes. Overall design: Examination of genes expressed by L. plantarum during fermentations of xyloglucans, human milk oligosaccharides and fructooligosaccharides in combination with two extracts of cranberry proanthocyanidins