Aronia berry polyphenols have matrix-dependent effects on the gut microbiota.

The objective of this study was to determine the extent that the aronia berry matrix affects gut microbiota composition, fecal short chain fatty acids (SCFAs), and colonic anthocyanins in healthy mice. C57BL/6J mice were fed AIN-93 M control diet (C) or C with whole aronia berry (AB), aronia extract (AE), or polyphenol-depleted AB (D) at the expense of cornstarch. After one week of feeding, AB and D increased fecal anthocyanins more than AE. Diets differentially affected SCFA and microbiota. AB fecal SCFA was associated with increased metabolism of succinate and pyruvate to butyrate. D increased acetic acid production, was associated with increased abundance of predicted genes for fermentation of carbohydrates to acetyl-coA. AB and D also increased predicted abundance of microbial catechol metabolism pathway I relative to C, which was attributed to enrichment of Lachnospiraceae. Therefore, the berry matrix impacts how aronia polyphenols interact with the gut microbiota in healthy mice.

Aronia berry inhibits disruption of Caco-2 intestinal barrier function.

The objective of this work was to determine how aronia berry polyphenols and its microbial catabolites improve intestinal barrier function. Caco-2 cells were cultured on transwell plates and allowed differentiate to form a model intestinal barrier, having baseline transepithelial electrical resistance (TEER) ≥ 300 Ω cm2. Barrier function of differentiated Caco-2 cells was compromised by the addition of an inflammatory cocktail (IC: TNF-α, IL-1ß, and IFN-γ to the basolateral media and lipopolysaccharide to the apical media). Polyphenol-rich aronia berry powder or individual polyphenols representative of parent compounds or catabolites were applied to the basolateral media concurrently with IC. TEER was determined subsequently by chopstick electrode or continuous analysis. Permeability was determined by application of 4 kDa FITC-dextran or Lucifer yellow. Expression of tight junction proteins was assessed by qRT-PCR analysis. Application of the IC to differentiated Caco-2 cells routinely reduced TEER by ~40% within 24 h. Individual polyphenols representative of parent compounds or phenolic microbial catabolites at 100 µM did not inhibit IC reduction of TEER in Caco-2 cells. Whole aronia berry powder inhibited loss of TEER by ~50% at 24 h after application of the IC. Furthermore 5 mg/mL of aronia berry powder prevented an IC-induced barrier permeability of FITC-dextran and Lucifer yellow. After 12 h of IC treatment, Caco-2 cells had increased claudin 1 (CLDN1) relative to the untreated control. Application of aronia berry powder inhibited CLDN1 and also increased expression of zonula ocludens-1 (ZO-1) after 12 h. In summary, aronia berry, but not its microbiota-derived catabolites improved intestinal barrier function in a cellular model of chronic colonic inflammation. In this case, improved barrier function was associated with modulation of tight junction expression.

Polyphenol Extracts from Three Colombian Passifloras (Passion Fruits) Prevent Inflammation-Induced Barrier Dysfunction of Caco-2 Cells.

Chronic intestinal inflammation is associated with pathophysiology of obesity and inflammatory bowel diseases. Gastrointestinal inflammation increases barrier dysfunction exacerbating the immune response and perpetuating chronic inflammation. Anti-inflammatory flavonoids may prevent this intestinal barrier dysfunction. The purpose of this study was to evaluate the polyphenol composition of Colombian Passiflora edulis var. Flavicarpa (Maracuyá), Passiflora edulis var. Sims (Gulupa), and Passiflora ligularis var. Juss (Granadilla) (passion fruits) and to evaluate their ability to inhibit disruption of intestinal barrier dysfunction of Caco-2 (colorectal adenocarcinoma) cells by an inflammatory cocktail (IC). Polyphenols (flavan-3-ols, phenolic acids, flavonols), xanthenes, and a terpene were identified in passion fruits. Cyanidin 3-rutinoside, (+)-catechin and ferulic acid were the most abundant phenolics in P. edulis var. Flavicarpa, P. edulis var. Sims, and P. ligularis var. Juss, respectively. Fruit extracts prevented loss of transepithelial electrical resistance in Caco-2 cells treated with the IC. Among the extracts, P. ligularis var. Juss was most effective at maintaining Caco-2 transepithelial electrical resistance (TEER) with ~73% relative to the IC-treated cells with about 43% of initial TEER values. This fruit had cyanidin-3-rutinoside, (+)-catechin, (-)-epicatechin, and ferulic acid in its phenolic profile. Results of this work support the hypothesis that consumption of passion fruit extracts could benefit intestinal health.

Aronia Berry Supplementation Mitigates Inflammation in T Cell Transfer-Induced Colitis by Decreasing Oxidative Stress.

Oxidative stress is involved in the pathogenesis and progression of inflammatory bowel disease. Consumption of aronia berry inhibits T cell transfer colitis, but the antioxidant mechanisms pertinent to immune function are unclear. We hypothesized that aronia berry consumption could inhibit inflammation by modulating the antioxidant function of immunocytes and gastrointestinal tissues. Colitis was induced in recombinase activating gene-1 deficient (Rag1-/-) mice injected with syngeneic CD4+CD62L+ naïve T cells. Concurrent with transfer, mice consumed either 4.5% w/w aronia berry-supplemented or a control diet for five weeks. Aronia berry inhibited intestinal inflammation evidenced by lower colon weight/length ratios, 2-deoxy-2-[18F]fluoro-d-glucose (FDG) uptake, mRNA expressions of tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) in the colon. Aronia berry also suppressed systemic inflammation evidenced by lower FDG uptake in the spleen, liver, and lung. Colitis induced increased colon malondialdehyde (MDA), decreased colon glutathione peroxidase (GPx) activity, reduced glutathione (rGSH) level, and suppressed expression of antioxidant enzymes in the colon and mesenteric lymph node (MLN). Aronia berry upregulated expression of antioxidant enzymes, prevented colitis-associated depletion of rGSH, and maintained GPx activity. Moreover, aronia berry modulated mitochondria-specific antioxidant activity and decreased splenic mitochondrial H2O2 production in colitic mice. Thus, aronia berry consumption inhibits oxidative stress in the colon during T cell transfer colitis because of its multifaceted antioxidant function in both the cytosol and mitochondria of immunocytes.

Dietary Prevention of Colitis by Aronia Berry is Mediated Through Increased Th17 and Treg.

SCOPE: Increased fruit consumption is associated with reduced risk of colitis. It has been investigated whether the anti-colitic effects of the polyphenol-rich aronia berry (Aronia mitschurinii 'Viking') are mediated through Th17 and Treg. METHODS AND RESULTS: Colitis is induced in recombinase activating gene-1 deficient mice injected with syngeneic CD4+ CD62L+ naïve T cells. Mice consume either 4.5% w/w aronia-berry-supplemented or a control diet concurrent with T cell transfer. The extent of colitis and immunocyte populations are evaluated at weeks 3 to 7 after transfer. Aronia consumption prevents colitic wasting and reduces colon weight/length ratios relative to the control diet at weeks 5 and 7. Compared to the control diet, aronia feeding increases Treg in mesenteric lymph node at all colitis stages. Treg and regulatory Th17 subpopulations (IL-17A+ IL-10+ and IL-17A+ IL-22+ ) are increased in lamina propria and spleen at week 5 in aronia-fed mice. Aronia feeding also decreases total CD4+ cells but increases colonic Tregs. The ability of aronia to modulate colonic cytokines is associated with functional T cell IL-10 and increased diversity of microbiota. CONCLUSIONS: Aronia berry consumption inhibits adoptive transfer colitis by increasing Treg and regulatory Th17 cells. Dietary modulation of T cells is dynamic and precedes colitic wasting.