Papers by Charlotte Grootaert

International Journal of Molecular Sciences
Fumonisin B1 (FB1) and aflatoxin B1 (AFB1) are frequent contaminants of staple foods such as maiz... more Fumonisin B1 (FB1) and aflatoxin B1 (AFB1) are frequent contaminants of staple foods such as maize. Oral exposure to these toxins poses health hazards by disrupting cellular signaling. However, little is known regarding the multifaced mitochondrial dysfunction-linked toxicity of FB1 and AFB1. Here, we show that after exposure to FB1 and AFB1, mitochondrial respiration significantly decreased by measuring the oxygen consumption rate (OCR), mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). The current work shows that the integrity of mitochondria (MMP and ROS), that is the central component of cell apoptosis, is disrupted by FB1 and AFB1 in undifferentiated Caco-2 and HepG2 cells as in vitro models for human intestine and liver, respectively. It hypothesizes that FB1 and AFB1 could disrupt the mitochondrial electron transport chain (ETC) to induce mitochondrial dysfunction and break the balance of transferring H+ between the mitochondrial inner membrane and mit...

Critical Reviews in Food Science and Nutrition, 2021
Flavonoid consumption has beneficial effects on human health, however, clinical evidence remains ... more Flavonoid consumption has beneficial effects on human health, however, clinical evidence remains often inconclusive due to high interindividual variability. Although this high interindividual variability has been consistently observed in flavonoid research, the potential underlying reasons are still poorly studied. Especially the knowledge on the impact of health status on flavonoid responsiveness is limited and merits more investigation. Here, we aim to highlight the bidirectional interplay between flavonoids and cellular stress. First, the state-of-the-art concerning inflammatory stress and mitochondrial dysfunction is reviewed and a comprehensive overview of recent in vitro studies investigating the impact of flavonoids on cellular stress, induced by tumor necrosis factor α, lipopolysaccharide and mitochondrial stressors, is given. Second, we critically discuss the influence of cellular stress on flavonoid uptake, accumulation, metabolism and cell responses, which has, to our knowledge, never been extensively reviewed before. Next, we advocate the innovative insight that stratification of the general population based on health status can reveal subpopulations that benefit more from flavonoid consumption. Finally, suggestions are given for the development of future cell models that simulate the physiological micro-environment, including interindividual variability, since more mechanistic research is needed to establish scientific-based personalized food recommendations for specific subpopulations.
Trends in Food Science & Technology

Journal of Hazardous Materials, 2021
Plastic pollution is a major issue worldwide, generating massive amounts of smaller plastic parti... more Plastic pollution is a major issue worldwide, generating massive amounts of smaller plastic particles, including microplastics (MPs). Their ubiquitous nature in the environment but also in foodstuff and consumer packaged goods has revealed potential threats to humans who can be contaminated mainly through air, food and water consumption. In this review, the current literature on human exposure to MPs is summarized with a focus on the gastrointestinal tract as portal of entry. Then, we discuss the vector effect of MPs, in their pristine versus weathered forms, with well-known contaminants as heavy metals and chemicals, or more emerging ones as antibiotics or microbial pathogens, like Pseudomonas spp., Vibrio spp., Campylobacter spp. and Escherichia coli. Comprehensive knowledge on MP fate in the gastrointestinal tract and their potential impact on gut homeostasis disruption, including gut microbiota, mucus and epithelial barrier, is reported in vitro and in vivo in mammals. Special emphasis is given on the crucial need of developing robust in vitro gut models to adequately simulate human digestive physiology and absorption processes. Finally, this review points out future research directions on MPs in human intestinal health.
Communications in agricultural and applied biological sciences, 2006
1. Commun Agric Appl Biol Sci. 2006;71(1):159-63. Arabinoxylan oligosaccharides with different st... more 1. Commun Agric Appl Biol Sci. 2006;71(1):159-63. Arabinoxylan oligosaccharides with different structures exert a bifidogenic effect in a mixed intestinal community. Grootaert C, Verstraete W, Van de Wiele T. Laboratory of Microbial Ecology and Technology, Ghent University, Belgium. PMID: 17191497 [PubMed - indexed for MEDLINE]. MeSH Terms. Bifidobacterium/enzymology; Bifidobacterium/growth & development*; Bifidobacterium/metabolism; ...
Ghent University Ghent University Academic Bibliography. ...
Food Research International
Food Research International

Foods
Although the fate of anthocyanins along digestion has been a matter of research over the last dec... more Although the fate of anthocyanins along digestion has been a matter of research over the last decade, their bioaccessibility so far has been mainly assessed for single administered fruits or vegetables, which is far from the real scenario where they are co-ingested in a meal. Accordingly, the aim of this study was to evaluate the effect of simultaneous intake of fruit and vegetable on in vitro stability, bioaccessibility and uptake of anthocyanins. Black carrot and strawberry were used as food sources of anthocyanins. Anthocyanin identification and quantification were performed using HPLC-Qtof/HPLC-UV. Single matrices and mixtures thereof, were submitted to a standardized in vitro digestion procedure. Anthocyanin uptake was evaluated through an intestinal Caco-2 cell model. Our results showed an increased intestinal stability for specific anthocyanins as a consequence of co-digestion. The presence of the strawberry food matrix positively affected the bioaccessibility of the carrot a...
Monatshefte für Chemie - Chemical Monthly
A small set of structurally different monocarbonyl curcuminoids was prepared and screened for cyt... more A small set of structurally different monocarbonyl curcuminoids was prepared and screened for cytotoxic activity. In particular, bis-3-methoxy-4-hydroxy- and bis-4-methoxyphenyl-substituted monocarbonyls were synthesized and transformed into the corresponding three-dimensional N-acetylpyrazoline derivatives. In addition, a non-symmetrical indole-based monocarbonyl curcumin was prepared as well. Preliminary cytotoxic evaluation revealed significant effects for 4-hydroxy (pyrazoline) monocarbonyl curcuminoids, whereas the non-phenolic variants displayed rather poor activity.

Molecular Nutrition & Food Research
SCOPE To explore the mechanisms behind the health effects of Aronia (Aronia melanocarpa), the mic... more SCOPE 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. RESULTS 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-α 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.

Food Research International
As the interface between the luminal and internal environment, the intestinal epithelium is stron... more As the interface between the luminal and internal environment, the intestinal epithelium is strongly exposed to food-related, host-related and microbial stress. Furthermore, the endothelial stress response plays an important role in vascular disease development, which may be improved upon consumption of dietary bioactives such as polyphenols. The impact of the latter, however, is largely individual-dependent and effects are, in most cases, only observed under mild diseased conditions. Here, it is hypothesized that the individual's stressor levels may contribute to this variable response. To this end, the impact of the stressors (i) valinomycin (as model for cereulide, food-related microbial metabolite), (ii) TNF-α (host-related) and (iii) lipopolysaccharide (gram-negative bacterial cell related) on flavonoid accumulation was investigated in several intestinal and endothelial cell lines. Flow cytometry, confocal microscopy and an in-house developed, robust and high-throughput spectrofluorometric method, showed that quercetin accumulated in all tested cell lines in a dose-dependent manner. Upon stress induced by valinomycin and to a lesser extent by lipopolysaccharide, but not by TNF-α, an increased quercetin accumulation was observed in proliferating intestinal and endothelial cells and not in differentiated intestinal or quiescent endothelial cells. Therefore, flavonoid accumulation may be a potential cellular stress response mechanism which strongly depends on the applied stressor, flavonoid, cell line and even growth conditions. This opens perspectives for further understanding the mechanisms by which cellular stress may shape the individual's response to bioactive compounds.
Chemistry – A European Journal

Nutrients
Citrus flavanones, with hesperidin and naringin as the most abundant representatives, have variou... more Citrus flavanones, with hesperidin and naringin as the most abundant representatives, have various beneficial effects, including anti-oxidative and anti-inflammatory activities. Evidence also indicates that they may impact the intestinal microbiome and are metabolized by the microbiota as well, thereby affecting their bioavailability. In this review, we provide an overview on the current evidence on the intestinal fate of hesperidin and naringin, their interaction with the gut microbiota, and their effects on intestinal barrier function and intestinal inflammation. These topics will be discussed as they may contribute to gastrointestinal health in various diseases. Evidence shows that hesperidin and naringin are metabolized by intestinal bacteria, mainly in the (proximal) colon, resulting in the formation of their aglycones hesperetin and naringenin and various smaller phenolics. Studies have also shown that citrus flavanones and their metabolites are able to influence the microbiot...
Biology of the Cell
In vivo oxygen levels in tissues range from 1% to 15%, while mechanistic cell culture studies emp... more In vivo oxygen levels in tissues range from 1% to 15%, while mechanistic cell culture studies employ an atmospheric oxygen level of 21% to grow cells. These oxygen concentrations are therefore not representative for conditions where the cell response is dependent on oxygen partial pressure. In pathological situation, such as (colon) cancer or chronic inflammation, tissue oxygenation is severely affected, and even under physiological conditions a steep oxygen gradient is present in the large intestine, where epithelial cells co‐exist with microbial species, resulting in almost anoxia at the midpoint of the lumen. In these situations, a better characterisation of the essential cellular behaviour under hypoxia or anoxia is required.
International Journal of Food Science & Technology
Extensive in vitro and, to a more limited extent, animal research have demonstrated the health po... more Extensive in vitro and, to a more limited extent, animal research have demonstrated the health potential of a wide set of egg protein hydrolysates; however, well-designed human intervention studies are scarce. Health claim assessment, however, sets high standards for characterisation of the bioactive peptides, investigation of the mode-of-action and convincing human intervention studies. In this review, we discuss the state-of-the-art and knowledge gaps related to egg-derived peptide bioavailability and bioactivity. In addition, we will formulate recommendations for appropriate design of future human intervention trials with egg-derived peptides.

ChemistryOpen
Curcumin is known to display pronounced anticancer effects and a variety of other biological acti... more Curcumin is known to display pronounced anticancer effects and a variety of other biological activities. However, the low bioavailability and fast metabolism of this molecule present an issue of concern with respect to its medicinal applications. To address this issue, structural modifications of the curcumin scaffold can be envisioned as a strategy to improve both the solubility and stability of this chemical entity, without compromising its biological activities. Previous work in our group targeted the synthesis of symmetrical azaheteroaromatic curcuminoids, which showed better solubility and cytotoxicity profiles compared to curcumin. In continuation of that work, we now focused on the synthesis of non-symmetrical nitrogencontaining curcuminoids bearing both a phenolic and an azaheteroaromatic moiety. In that way, we aimed to combine good solubility, antioxidant potential and cytotoxic properties into one molecule. Some derivatives were selected for further chemical modification of their rather labile β-diketone scaffold to the corresponding pyrazole moiety. In this way, thirteen new non-symmetrical aza-aromatic curcuminoids and four pyrazolebased analogues were successfully synthesized in a yield of 11-69 %. All newly synthesized analogues were evaluated for their antioxidant properties, reactive oxygen species (ROS) production, water solubility and anticancer activities. Several novel derivatives displayed good cytotoxicity profiles compared to curcumin, in combination with an improved water solubility and stability, and were thus identified as potential hit scaffolds for further optimization studies.

International Journal of Biological Macromolecules
Quercetin-fortified nanoparticles were prepared from almond gum (AG), a novel biological macromol... more Quercetin-fortified nanoparticles were prepared from almond gum (AG), a novel biological macromolecule, and Tween 80 (T80) as stabilizers and shellac (SH) as core material using an antisolvent precipitation method. The final nanoparticles were prepared by 0.67% SH, 0.02% Q, 0.5% AG and 0.1% w/v T80 using the stirring speed of 750 rpm at a dosing rate of 0.5 ml/min. The morphology of the particles was characterized using Cryo-SEM and TEM microscopy. The average particle size was 135 ± 8 nm with a polydispersity index of 0.252 ± 0.01 and an encapsulation efficiency of 97.7 ± 1.2%. At pH 7.4 (intestinal pH), quercetin-loaded nanoparticles showed significantly (p < 0.05) higher antioxidant activity compared to free quercetin while the degradation of quercetin was lower in the nanoparticles compared to free quercetin at the similar pH. Quercetin loaded in nanoparticles was successfully found to be 2 times more available for uptake than free quercetin at pH 7.4. MTT and SRB assays revealed that no significant (p > 0.05) toxicity was observed for Caco-2 cells treated with quercetin-loaded nanoparticles with a dilution factor of 100. This study provides information about the formulation of promising nanocarriers using biological macromolecules for oral delivery of bioactive compounds.
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Papers by Charlotte Grootaert