Proanthocyanidin-enriched cranberry extract induces resilient bacterial community dynamics in a gnotobiotic mouse model

Cranberry consumption has numerous health benefits, with experimental reports showing its anti-inflammatory and anti-tumor properties. Importantly, microbiome research has demonstrated that the gastrointestinal bacterial community modulates host immunity, raising the question of whether the cranberry-derived effect may be related to its ability to modulate the microbiome. Only a few studies have investigated the effect of cranberry products on the microbiome to date. Especially because cranberries are rich in dietary fibers, the extent of microbiome modulation by polyphenols, particularly proanthocyanidins (PACs), remains to be shown. Since previous work has only focused on long-term effects of cranberry extracts, in this study we investigated the effect of a water-soluble, PAC-rich cranberry juice extract (CJE) on the short-term dynamics of a human-derived bacterial community in a gnotobiotic mouse model. CJE characterization revealed a high enrichment in PACs (57%), the highest ever utilized in a microbiome study. In a 37-day experiment with a ten-day CJE intervention and 14-day recovery phase, we profiled the microbiota via 16S rRNA sequencing and applied diverse time-series analytics methods to identify individual bacterial responses. We show that daily administration of CJE induces distinct dynamic patterns in bacterial abundances during and after treatment, before recovering resiliently to pre-treatment levels. Specifically, we observed an increase of Akkermansia muciniphila and Clostridium hiranonis at the expense of Bacteroides ovatus after the offset of the selection pressure imposed by the PAC-rich CJE. This demonstrates that termination of an intervention with a cranberry product can induce changes of a magnitude as high as the intervention itself.