Scope Results To explore the mechanisms behind the health effects of Aronia (Aronia melanocarpa), the microbial community modulating and anti-inflammatory effects of Aronia polyphenols are investigated by combining the similutor of the human intestinal microbial ecosystem (SHIME) with a coculture of intestinal and endothelial cells. Administration of Aronia juice (6.5g L-1) to the SHIME for 2 weeks increases the abundance of firmicutes to 92% in the ascending colon (AC), 85% in the transverse colon (TC), and 82% in the descending colon (DC; p < 0.001), proteobacteria (6.7% in AC, p < 0.001), and Akkermansia (14% in TC and 18% in DC, p < 0.001) and decreases the abundance of Bifidobacterium species, associated with a decrease of acetate and increase of propionate and butyrate, whereas no significant difference is observed upon placebo juice treatment. After addition of the digests to TNF-alpha challenged Caco-2/endothelial cocultures, intercellular adhesion molecule (ICAM)-1, IL-8, and monocyte chemoattractant protein-1 levels are significantly downregulated. Interestingly, Aronia juice treats digests from each colon compartment resulting in a stronger decrease of the ICAM-1 secretion (up to 73%, p < 0.001) compared to their corresponding placebo treated digests, thereby pointing to a polyphenol-dependent effect. Conclusions Aronia polyphenols modulate intestinal microbial composition, induce beneficial short chain fatty acid production, and prevent inflammatory stress in endothelial cells. This opens perspectives for the use of Aronia polyphenols as prebiotics in the context of intestinal and cardiovascular health.