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A critical evaluation of in vitro hesperidin 2S bioavailability in a model combining luminal (microbial) digestion and Caco-2 cell absorption in comparison to a randomized controlled human trial

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Abstract
Scope: Bioavailability strongly determines polyphenol bioactivity, and is strongly influenced by food matrix, enzymatic and microbial degradation, and gastrointestinal absorption. To avoid human trials for pre-screening of polyphenol bioavailability, studies have focused on in vitro model development. Nevertheless, their predictive value for bioavailability can be questioned. Method and results: We used the orange flavonoid hesperidin 2S to validate a model combining digestion in the simulator of the human intestinal microbial ecosystem (SHIME) and Caco-2 cell transport, with a human intervention study. In vitro, hesperidin was resistant to degradation in the stomach and small intestine, but was rapidly deconjugated on reaching the proximal colon. Extensive and colon-region-specific degradation to smaller phenolics was observed. Hydrocaffeic and dihydroisoferulic acid accumulated in proximal, and hydroferulic acid in distal colon. Caco-2 transport was the highest for dihydroisoferulic acid. In humans, plasma and urine hesperetin-glucuronide levels increased significantly, whereas the impact on small phenolics was limited. Conclusions: In the combined in vitro model, smaller phenolics strongly accumulated, whereas in humans, hesperetin conjugates were the main bioavailable compounds. Future in vitro model development should focus on simulating faster polyphenol absorption and elimination of smaller phenolics to improve their predictive value of in vivo polyphenol bioavailability.
Keywords
SHIME®, Caco-2, bioavailability, human, microbiota, ORANGE JUICE (POLY)PHENOLS, HEALTHY HUMANS, HESPERETIN, NARINGENIN, FLAVANONES, PLASMA, CITRUS, ACID, PHARMACOKINETICS, OLIGOSACCHARIDES

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MLA
Van Rymenant, Evelien et al. “A Critical Evaluation of in Vitro Hesperidin 2S Bioavailability in a Model Combining Luminal (microbial) Digestion and Caco-2 Cell Absorption in Comparison to a Randomized Controlled Human Trial.” MOLECULAR NUTRITION & FOOD RESEARCH 62.8 (2018): n. pag. Print.
APA
Van Rymenant, E., Salden, B., Voorspoels, S., Jacobs, G., Noten, B., Pitart, J., Possemiers, S., et al. (2018). A critical evaluation of in vitro hesperidin 2S bioavailability in a model combining luminal (microbial) digestion and Caco-2 cell absorption in comparison to a randomized controlled human trial. MOLECULAR NUTRITION & FOOD RESEARCH, 62(8).
Chicago author-date
Van Rymenant, Evelien, Bouke Salden, Stefan Voorspoels, Griet Jacobs, Bart Noten, Judit Pitart, Sam Possemiers, Guy Smagghe, Charlotte Grootaert, and John Van Camp. 2018. “A Critical Evaluation of in Vitro Hesperidin 2S Bioavailability in a Model Combining Luminal (microbial) Digestion and Caco-2 Cell Absorption in Comparison to a Randomized Controlled Human Trial.” Molecular Nutrition & Food Research 62 (8).
Chicago author-date (all authors)
Van Rymenant, Evelien, Bouke Salden, Stefan Voorspoels, Griet Jacobs, Bart Noten, Judit Pitart, Sam Possemiers, Guy Smagghe, Charlotte Grootaert, and John Van Camp. 2018. “A Critical Evaluation of in Vitro Hesperidin 2S Bioavailability in a Model Combining Luminal (microbial) Digestion and Caco-2 Cell Absorption in Comparison to a Randomized Controlled Human Trial.” Molecular Nutrition & Food Research 62 (8).
Vancouver
1.
Van Rymenant E, Salden B, Voorspoels S, Jacobs G, Noten B, Pitart J, et al. A critical evaluation of in vitro hesperidin 2S bioavailability in a model combining luminal (microbial) digestion and Caco-2 cell absorption in comparison to a randomized controlled human trial. MOLECULAR NUTRITION & FOOD RESEARCH. 2018;62(8).
IEEE
[1]
E. Van Rymenant et al., “A critical evaluation of in vitro hesperidin 2S bioavailability in a model combining luminal (microbial) digestion and Caco-2 cell absorption in comparison to a randomized controlled human trial,” MOLECULAR NUTRITION & FOOD RESEARCH, vol. 62, no. 8, 2018.
@article{8550745,
  abstract     = {Scope: Bioavailability strongly determines polyphenol bioactivity, and is strongly influenced by food matrix, enzymatic and microbial degradation, and gastrointestinal absorption. To avoid human trials for pre-screening of polyphenol bioavailability, studies have focused on in vitro model development. Nevertheless, their predictive value for bioavailability can be questioned. 
Method and results: We used the orange flavonoid hesperidin 2S to validate a model combining digestion in the simulator of the human intestinal microbial ecosystem (SHIME) and Caco-2 cell transport, with a human intervention study. In vitro, hesperidin was resistant to degradation in the stomach and small intestine, but was rapidly deconjugated on reaching the proximal colon. Extensive and colon-region-specific degradation to smaller phenolics was observed. Hydrocaffeic and dihydroisoferulic acid accumulated in proximal, and hydroferulic acid in distal colon. Caco-2 transport was the highest for dihydroisoferulic acid. In humans, plasma and urine hesperetin-glucuronide levels increased significantly, whereas the impact on small phenolics was limited. 
Conclusions: In the combined in vitro model, smaller phenolics strongly accumulated, whereas in humans, hesperetin conjugates were the main bioavailable compounds. Future in vitro model development should focus on simulating faster polyphenol absorption and elimination of smaller phenolics to improve their predictive value of in vivo polyphenol bioavailability.},
  articleno    = {1700881},
  author       = {Van Rymenant, Evelien and Salden, Bouke and Voorspoels, Stefan and Jacobs, Griet and Noten, Bart and Pitart, Judit and Possemiers, Sam and Smagghe, Guy and Grootaert, Charlotte and Van Camp, John},
  issn         = {1613-4125},
  journal      = {MOLECULAR NUTRITION & FOOD RESEARCH},
  keywords     = {SHIME®,Caco-2,bioavailability,human,microbiota,ORANGE JUICE (POLY)PHENOLS,HEALTHY HUMANS,HESPERETIN,NARINGENIN,FLAVANONES,PLASMA,CITRUS,ACID,PHARMACOKINETICS,OLIGOSACCHARIDES},
  language     = {eng},
  number       = {8},
  pages        = {11},
  title        = {A critical evaluation of in vitro hesperidin 2S bioavailability in a model combining luminal (microbial) digestion and Caco-2 cell absorption in comparison to a randomized controlled human trial},
  url          = {http://dx.doi.org/10.1002/mnfr.201700881},
  volume       = {62},
  year         = {2018},
}

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