Comparison of in vivo and in vitro digestion of polyphenol composition in lingonberries: potential impact on colonic health

Abstract

Evidence from epidemiological studies suggests that diets rich in fruit and vegetables may contribute to a reduced risk of colorectal cancer (CRC). A recent meta-analysis of risk factors associated with colorectal cancer reported a decreased risk associated with fruit consumption (RR = 0·85, 95% CI = 0·75-0·96 for 3 servings/day) and also emphasized that low fruit and vegetable consumption was associated with a moderately increased risk of CRC (1) . Lingonberry (Vaccinium vitis-idaea L) is a popular edible berry in Scandinavian countries and is increasing in popularity across Europe. Lingonberry possesses a complex (poly)phenolic profile, which may contribute to its putative anticancer activity. Following consumption and digestion, limited uptake from the small intestine results in berry (poly)phenolic compounds entering the colon, where they are subject to microbiota-mediated metabolism (2) . Therefore, it is likely that the colonic epithelium is exposed to phenolic metabolites as well as the original parent compounds.The aim of this study was to evaluate the impact of in vivo and in vitro digestion on phenolic composition and bioactivity of lingon berries. Lingonberry extracts obtained after simulated in vitro digestion (IVDL) and subsequent faecal fermentation (IVFL) were compared to samples of ileal fluid (IF) obtained from an ileostomist (3) pre & post lingonberry consumption 150 g (ID 12/WS/0192). Bioactivity of the extracts was tested using a physiologically-relevant dose range (0-50 μg/ml gallic acid equivalents) over a 24 hour exposure period using in vitro colonocyte models of colorectal carcinogenesis (Comet assay HT29, mutagenicity assay HT29G 17 neo, Matrigel invasion assay HT115) (4) . LC-MS analysis confirmed that in vitro digestion altered the (poly)phenol composition relative to the original lingonberry and similar patterns were observed for the ileal fluid. On the other hand, the IVFL sample had high levels of simple aromatic components. Digested and fermented extracts exhibited significant (p < 0·05) anti-genotoxic, antimutagenic and anti-invasive effects compared to the appropriate controls (ANOVA, Post Hoc Dunnett T test) in all in vitro models. The ileal fluid demonstrated a significant reduction in DNA damage (p < 0·05), but at a higher total polyphenol concentration (μg/ml GAE/ml) than the IVDL. Despite extensive structural modification following digestion and fermentation, lingonberry extracts retained their bioactivity. These data reinforce the need for screening studies to consider the impact of digestion when investigating bioactivity of dietary phytochemicals.

Effect of simulated gastrointestinal digestion and fermentation on polyphenolic content and bioactivity of brown seaweed phlorotannin‐rich extracts

“…In addition, after CF all extracts showed a further reduction of TP and antioxidant capacity, thus they were able to significantly reduce H 2 O 2 -induced DNA damage, indicating how the potential beneficial effects of the extracts are not linked to their in vitro antioxidant potential. Our results are consistent with observations of (poly)phenolic compounds from other terrestrial dietary sources [53][54][55][56]. Our results also highlight the strong impact of GID and CF on the ability of the extracts to induce cell growth inhibition on HT-29 cells.…”

Anthocyanin extracts of lingonberry (Vaccinium vitis‐idaea L.) attenuate serum lipids and cholesterol metabolism in HCD‐induced hypercholesterolaemic male mice

“…Based on the previous report by Brown et al . (), this chemical structure was presumed to be cyanidin‐3‐O‐galactoside. Other anthocyanins such as cyanidin‐rutinoside (peak 4) and peonidin‐galactoside/glucoside (peak 5) were also detected at much lower quantities.…”

“…After being introduced into Lesser Khingan and Greater Higgnan Mountains area of China, lingonberry has become a common fruit on the table of local people (Fan et al ., ). In recent years, many reports have been published on the structure of lingonberry anthocyanins and polyphenols (Kylli et al ., ; Szakiel et al ., ; Ieri et al ., ), and high biological activities against several diseases including hypertension, oxidative stress, obesity and colonic health has been found in lingonberry extract or lingonberry juice (Kivimaki et al ., ; Eid et al ., ; Brown et al ., ; Drozdz et al ., ). However, most of the studies are focused on the lingonberry grown in northern Europe and only few reports used Chinese lingonberry as the experimental materials.…”

Correlation between in vitro and in vivo data on food digestion. What can we predict with static in vitro digestion models?

“…Nevertheless, a few studies have compared their in vitro bioaccessibility with in vivo human trials. Brown et al investigated the polyphenol composition of lingonberries following both in vitro (including faecal fermentation) and in vivo digestion in ileostomists (Brown et al, 2014). Certain differences in polyphenol composition were found between the ileal efflux and the bioaccessible fraction in vitro, and were explained by the absence of brush-border enzymes, e.g.…”