Immunomodulatory Effects of Aronia Juice Polyphenols—Results of a Randomized Placebo-Controlled Human Intervention Study and Cell Culture Experiments

Abstract

Dietary polyphenols, which are present in Aronia melanocarpa, have been associated with various beneficial effects on human health including antioxidant, antiviral, and anti-inflammatory activities. We aimed to investigate the immunomodulatory effects of aronia juice polyphenols in a randomized placebo-controlled human intervention study and cell culture experiments. A total of 40 females were asked to consume either 200 mL of aronia juice or a placebo drink for six weeks and were investigated again after a washout period of another six weeks. We observed that only half of the participants tolerated the aronia juice well (Vt) and the other half reported complaints (Vc). The placebo (P) was generally tolerated with one exception (p = 0.003). Plasma polyphenol levels increased significantly in Vt after the intervention (p = 0.024) but did neither in P nor in Vc. Regulatory T cell (Treg) frequencies remained constant in Vt and P during the intervention, whereas Tregs decreased in Vc (p = 0.018). In cell culture, inhibiting effects of ferulic acid (p = 0.0005) and catechin (p = 0.0393) on the differentiation of Tregs were observed as well as reduced activation of CD4-T cells in ferulic acid (p = 0.0072) and aronia juice (p = 0.0163) treated cells. Interestingly, a CD4+CD25-FoxP3+ cell population emerged in vitro in response to aronia juice, but not when testing individual polyphenols. In conclusion, our data strengthen possible individual hormetic effects, the importance of the food matrix for bioactivity, and the need for further investigations on possible impacts of specific physiological features such as the gut microbiota in the context of personalized nutrition.

Interindividual differences in aronia juice tolerability linked to gut microbiome and metabolome changes—secondary analysis of a randomized placebo-controlled parallel intervention trial

“…We conducted a to the participants single-blinded placebo-controlled human intervention study in parallel design to investigate the effects of aronia juice polyphenols in a healthy, normal weight, female cohort to assess potential alterations of the gut microbiome composition and the metabolic profile. Since the aronia juice was tolerated differently in the verum group [32], we aimed to identify a potential mechanistic contribution of the gut microbiome on the tolerability of the aronia juice.…”

“…Moreover, the acceptance of aronia products is inconsistent mainly due to the astringent, bitter, and sour taste which is attributed to the phenolic components such as tannins [30,31]. Additionally, we recently described mixed tolerability of aronia juice and found a diverse response to an aronia juice intervention in a cohort of young healthy females [32]. Half of the participants tolerated the aronia juice well, whereas the other half reported gastrointestinal complaints after aronia juice consumption.…”

The Role of Anthocyanins in Alleviating Intestinal Diseases: A Mini Review

“…80 In addition, the participation of dietary anthocyanins in immune metabolism has been a hot academic topic. They can activate immune cells and their functions and regulate immune cell pathways, such as suppressing IL-6, and IL-8 expression, 71 promoting secretion and expression of antiinflammatory cytokines like IL-10R and IL-22, and inducing the production of regulatory T cells, thus enhancing the TJ function and maintaining intestinal barrier integrity 47,81 (Figure 3).…”

“…Anthocyanin treatment may induce the production of SCFAs which also play an immunomodulatory role in promoting the proliferation of mucosal regulatory T cells (Tregs) by interacting with G-protein-coupled receptors (GRP43) and inhibiting histone deacetylases (HDACS) . Tregs represent a special subgroup of T cells, a critical factor in regulating self-tolerance and homeostasis . The development of Treg not only induces the development of anti-inflammatory cytokines, such as IL-10, but also is related to the production of immunoglobulin A (IgA), an important anti-inflammatory antibody, which can achieve anti-inflammatory effects.…”

“…33 Tregs represent a special subgroup of T cells, a critical factor in regulating self-tolerance and homeostasis. 81 The development of Treg not only induces the development of anti-inflammatory cytokines, 63 such as IL-10, but also is related to the production of immunoglobulin A (IgA), an important anti-inflammatory antibody, which can achieve anti-inflammatory effects. Meanwhile, Tregs specifically regulated the expression of mucin-2 (MUC2) in goblet cells, increased mucus secretion, and enhanced the mucosal barrier.…”