Seaweed Components' Modulators Potential: Comparison
Please note this is a comparison between Version 2 by Ron Wang and Version 1 by Emer Shannon.

Macroalgae, or seaweeds, are a rich source of components which may exert beneficial effects on the mammalian gut microbiota through the enhancement of bacterial diversity and abundance. An imbalance of gut bacteria has been linked to the development of disorders such as inflammatory bowel disease, immunodeficiency, hypertension, type-2-diabetes, obesity, and cancer. This review outlines current knowledge from in vitro and in vivo studies concerning the potential therapeutic application of seaweed-derived polysaccharides, polyphenols and peptides to modulate the gut microbiota through diet. Polysaccharides such as fucoidan, laminarin, alginate, ulvan and porphyran are unique to seaweeds. Several studies have shown their potential to act as prebiotics and to positively modulate the gut microbiota. Prebiotics enhance bacterial populations and often their production of short chain fatty acids, which are the energy source for gastrointestinal epithelial cells, provide protection against pathogens, influence immunomodulation, and induce apoptosis of colon cancer cells. The oral bioaccessibility and bioavailability of seaweed components is also discussed, including the advantages and limitations of static and dynamic in vitro gastrointestinal models versus ex vivo and in vivo methods. Seaweed bioactives show potential for use in prevention and, in some instances, treatment of human disease. 

  • seaweed
  • prebiotics
  • gut microbiota
  • polysaccharides
  • polyphenols
  • peptides
  • colonic fermentation
  • short chain fatty acids
  • bioaccessibility
  • simulated gastrointestinal and fermentation digestion models
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References

  1. Feng, W.; Hu, Y.; An, N.; Feng, Z.; Liu, J.; Mou, J.; Hu, T.; Guan, H.; Zhang, D.; Mao, Y. Alginate oligosaccharide alleviates monocrotaline-induced pulmonary hypertension via anti-oxidant and anti-inflammation pathways in rats. Int. Heart J. 2020, 61, 160–168.
  2. Cotas, J.; Marques, V.; Afonso, M.B.; Rodrigues, C.M.; Pereira, L. Antitumour potential of Gigartina pistillata carrageenans against colorectal cancer stem cell-enriched tumourspheres. Mar. Drugs 2020, 18, 50.
  3. Pacheco, L.V.; Parada, J.; Pérez-Correa, J.R.; Mariotti-Celis, M.S.; Erpel, F.; Zambrano, A.; Palacios, M. Bioactive polyphenols from southern Chile seaweed as inhibitors of enzymes for starch digestion. Mar. Drugs 2020, 18, 353.
  4. Lee, H.-G.; Lu, Y.A.; Li, X.; Hyun, J.-M.; Kim, H.-S.; Lee, J.J.; Kim, T.H.; Kim, H.M.; Kang, M.-C. Anti-obesity effects of Grateloupia elliptica, a red seaweed, in mice with high-fat diet-induced obesity via suppression of adipogenic factors in white adipose tissue and increased thermogenic factors in brown adipose tissue. Nutrients 2020, 12, 308.
  5. Pimentel, F.B.; Cermeño, M.; Kleekayai, T.; Harnedy, P.A.; FitzGerald, R.J.; Alves, R.C.; Oliveira, M.B.P. Effect of in vitro simulated gastrointestinal digestion on the antioxidant activity of the red seaweed Porphyra dioica. Food Res. Int. 2020, 136, 109309.
  6. Irwin, Z.; McSorley, E.M.; Slevin, M.M.; Rowan, L.; McMillen, P.; McCullagh, D.; Magee, P.J.; Gill, C.I.; Cherry, P.; Crowe, W. The effect of a fibre extract from the red seaweed, Palmaria palmata, on lipid metabolism and inflammation in healthy adults. Proc. Nutr. Soc. 2020, 79.
  7. Seca, A.M.; Pinto, D.C. Overview on the antihypertensive and anti-obesity effects of secondary metabolites from seaweeds. Mar. Drugs 2018, 16, 237.
  8. Collins, K.G.; Fitzgerald, G.F.; Stanton, C.; Ross, R.P. Looking beyond the terrestrial: The potential of seaweed derived bioactives to treat non-communicable diseases. Mar. Drugs 2016, 14, 60.
  9. Garcia-Vaquero, M.; Mora, L.; Hayes, M. In vitro and in silico approaches to generating and identifying angiotensin-converting enzyme I inhibitory peptides from green macroalga Ulva lactuca. Mar. Drugs 2019, 17, 204.
  10. Charoensiddhi, S.; Conlon, M.A.; Vuaran, M.S.; Franco, C.M.M.; Zhang, W. Polysaccharide and phlorotannin-enriched extracts of the brown seaweed Ecklonia radiata influence human gut microbiota and fermentation in vitro. J. Appl. Phycol. 2017, 29, 2407–2416.
  11. Dobrinčić, A.; Balbino, S.; Zorić, Z.; Pedisić, S.; Bursać Kovačević, D.; Elez Garofulić, I.; Dragović-Uzelac, V. Advanced technologies for the extraction of marine brown algal polysaccharides. Mar. Drugs 2020, 18, 168.
  12. Hao, T. Research advances on the chemical structures and medicinal values of seaweed polysaccharides. J. Anhui Agric. Sci. 2018, 2018, 14. Available online: (accessed on 11 May 2020).
  13. Wijesinghe, W.A.J.P.; Jeon, Y.-J. Biological activities and potential cosmeceutical applications of bioactive components from brown seaweeds: A review. Phytochem. Rev. 2011, 10, 431–443.
  14. Salehi, B.; Sharifi-Rad, J.; Seca, A.M.L.; Pinto, D.C.G.A.; Michalak, I.; Trincone, A.; Mishra, A.P.; Nigam, M.; Zam, W.; Martins, N. Current trends on seaweeds: Looking at chemical composition, phytopharmacology, and cosmetic applications. Molecules 2019, 24, 4182.
  15. Rosa, G.P.; Tavares, W.R.; Sousa, P.M.C.; Pagès, A.K.; Seca, A.M.L.; Pinto, D.C.G.A. Seaweed secondary metabolites with beneficial health effects: An overview of successes in in vivo studies and clinical trials. Mar. Drugs 2019, 18, 8.
  16. Marzullo, P.; Di Renzo, L.; Pugliese, G.; De Siena, M.; Barrea, L.; Muscogiuri, G.; Colao, A.; Savastano, S. From obesity through gut microbiota to cardiovascular diseases: A dangerous journey. Int. J. Obes. Suppl. 2020, 10, 35–49.
  17. Barko, P.C.; McMichael, M.A.; Swanson, K.S.; Williams, D.A. The gastrointestinal microbiome: A Review. J. Vet. Intern. Med. 2018, 32, 9–25.
  18. Milani, C.; Duranti, S.; Bottacini, F.; Casey, E.; Turroni, F.; Mahony, J.; Belzer, C.; Delgado Palacio, S.; Arboleya Montes, S.; Mancabelli, L.; et al. The first microbial colonizers of the human gut: Composition, activities, and health implications of the infant gut microbiota. Microbiol. Mol. Biol. Rev. 2017, 81, e00036-17.
  19. Rinninella, E.; Raoul, P.; Cintoni, M. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms 2019, 7, 14.
  20. Flint, H.J. Chapter 6-Variability and stability of the human gut microbiome. In Why Gut Microbes Matter: Understanding Our Microbiome; Flint, H., Ed.; Springer Nature: Cham, Switzerland, 2020; pp. 63–79.
  21. Arumugam, M.; Raes, J.; Pelletier, E.; Le Paslier, D.; Yamada, T.; Mende, D.R.; Fernandes, G.R.; Tap, J.; Bruls, T.; Batto, J.-M.; et al. Enterotypes of the human gut microbiome. Nature 2011, 473, 174–180.
  22. Özgün, C.O.U.; Knut, R.; Dzung, B.D. Modulation of the gut microbiota by prebiotic fibres and bacteriocins. Microb. Ecol. Health Dis. 2017, 28, 1348886.
  23. Busnelli, M.; Manzini, S. The gut microbiota affects host pathophysiology as an endocrine organ: A focus on cardiovascular disease. Nutrients 2020, 12, 79.
  24. Markowiak-Kopeć, P.; Śliżewska, K. The effect of probiotics on the production of short-chain fatty acids by human intestinal microbiome. Nutrients 2020, 12, 1107.
  25. Parada Venegas, D.; De la Fuente, M.K.; Landskron, G.; González, M.J.; Quera, R.; Dijkstra, G.; Harmsen, H.J.; Faber, K.N.; Hermoso, M.A. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front. Immunol. 2019, 10, 277.
  26. Silva, Y.P.; Bernardi, A.; Frozza, R.L. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front. Endocrinol. 2020, 11, 25.
  27. Chambers, E.S.; Preston, T.; Frost, G.; Morrison, D.J. Role of gut microbiota-generated short-chain fatty acids in metabolic and cardiovascular health. Curr. Nutr. Rep. 2018, 7, 198–206.
  28. Carding, S.; Verbeke, K.; Vipond, D.T.; Corfe, B.M.; Owen, L.J. Dysbiosis of the gut microbiota in disease. Microb. Ecol. Health Dis. 2015, 26, 26191.
  29. Ganesan, K.; Chung, S.K.; Vanamala, J.; Xu, B. Causal relationship between diet-induced gut microbiota changes and diabetes: A novel strategy to transplant Faecalibacterium prausnitzii in preventing diabetes. Int. J. Mol. Sci. 2018, 19, 3720.
  30. Levy, M.; Kolodziejczyk, A.A.; Thaiss, C.A.; Elinav, E. Dysbiosis and the immune system. Nat. Rev. Immunol. 2017, 17, 219–232.
  31. Rowin, J.; Xia, Y.; Jung, B.; Sun, J. Gut inflammation and dysbiosis in human motor neuron disease. Physiol. Rep. 2017, 5, e13443.
  32. Zhao, L.; Zhang, F.; Ding, X.; Wu, G.; Lam, Y.Y.; Wang, X.; Fu, H.; Xue, X.; Lu, C.; Ma, J.; et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 2018, 359, 1151–1156.
  33. Charoensiddhi, S.; Abraham, R.E.; Su, P.; Zhang, W. Chapter Four-Seaweed and seaweed-derived metabolites as prebiotics. In Advances in Food and Nutrition Research; Toldrá, F., Ed.; Academic Press: Cambridge, MA, USA, 2020; Volume 91, pp. 97–156.
  34. Hu, B.; Gong, Q.; Wang, Y.; Ma, Y.; Li, J.; Yu, W. Prebiotic effects of neoagaro-oligosaccharides prepared by enzymatic hydrolysis of agarose. Anaerobe 2006, 12, 260–266.
  35. Alam, M.A.; Parra-Saldivar, R.; Bilal, M.; Afroze, C.A.; Ahmed, M.N.; Iqbal, H.M.N.; Xu, J. Algae-derived bioactive molecules for the potential treatment of SARS-CoV-2. Molecules 2021, 26, 2134.
  36. Ajanth Praveen, M.; Karthika Parvathy, K.R.; Jayabalan, R.; Balasubramanian, P. Dietary fiber from Indian edible seaweeds and its in-vitro prebiotic effect on the gut microbiota. Food Hydrocoll. 2019, 96, 343–353.
  37. Kawabata, K.; Yoshioka, Y.; Terao, J. Role of intestinal microbiota in the bioavailability and physiological functions of dietary polyphenols. Molecules 2019, 24, 370.
  38. Quigley, E.M.M. Prebiotics and probiotics in digestive health. Clin. Gastroenterol. Hepatol. 2019, 17, 333–344.
  39. Coelho, M.C.; Ribeiro, T.B.; Oliveira, C.; Batista, P.; Castro, P.; Monforte, A.R.; Rodrigues, A.S.; Teixeira, J.; Pintado, M. In vitro gastrointestinal digestion impact on the bioaccessibility and antioxidant capacity of bioactive compounds from tomato flours obtained after conventional and ohmic heating extraction. Foods 2021, 10, 554.
  40. Neal, M.J. Chap 3-Drug absorption, distribution and excretion In Medical Pharmacology at a Glance, 9th ed.; Neal, M.J., Ed.; John Wiley & Sons: Oxford, UK, 2020; Available online: (accessed on 15 May 2020).
  41. Srinivasan, V.S. Bioavailability of nutrients: A practical approach to in vitro demonstration of the availability of nutrients in multivitamin-mineral combination products. J. Nutr. 2001, 131, 1349S–1350S.
  42. Fernández-García, E.; Carvajal-Lérida, I.; Pérez-Gálvez, A. In vitro bioaccessibility assessment as a prediction tool of nutritional efficiency. Nutr. Res. 2009, 29, 751–760.
  43. Santos, D.I.; Saraiva, J.M.A.; Vicente, A.A.; Moldão-Martins, M. Chapter 2-Methods for determining bioavailability and bioaccessibility of bioactive compounds and nutrients. In Innovative Thermal and Non-Thermal Processing, Bioaccessibility and Bioavailability of Nutrients and Bioactive Compounds; Barba, F.J., Saraiva, J.M.A., Cravotto, G., Lorenzo, J.M., Eds.; Woodhead Publishing: Cambridge, UK, 2019; pp. 23–54.
  44. Pozharitskaya, O.N.; Shikov, A.N.; Faustova, N.M.; Obluchinskaya, E.D.; Kosman, V.M.; Vuorela, H.; Makarov, V.G. Pharmacokinetic and tissue distribution of fucoidan from Fucus vesiculosus after oral administration to rats. Mar. Drugs 2018, 16, 132.
  45. Nishikawa, T.; Yokose, T.; Yamamoto, Y.; Yamaguchi, K.; Oda, T. Detection and pharmacokinetics of alginate oligosaccharides in mouse plasma and urine after oral administration by a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. Biosci. Biotechnol. Biochem. 2008, 72, 2184–2190.
  46. Ventura, S.; Rodrigues, M.; Falcão, A.; Alves, G. Safety evidence on the administration of Fucus vesiculosus L. (bladderwrack) extract and lamotrigine: Data from pharmacokinetic studies in the rat. Drug Chem. Toxicol. 2020, 43, 560–566.
  47. Zhang, E.; Chu, F.; Zhao, T.; Chai, Y.; Liang, H.; Song, S.; Ji, A. Determination of fucoidan in rat plasma by HPLC and its application in pharmacokinetics. Pak. J. Pharm. Sci. 2020, 33.
  48. Lu, J.; Pan, Q.; Zhou, J.; Weng, Y.; Chen, K.; Shi, L.; Zhu, G.; Chen, C.; Li, L.; Geng, M.; et al. Pharmacokinetics, distribution, and excretion of sodium oligomannate, a recently approved anti-Alzheimer’s disease drug in China. J. Pharm. Anal. 2021.
  49. Pozharitskaya, O.N.; Shikov, A.N.; Obluchinskaya, E.D.; Vuorela, H. The pharmacokinetics of fucoidan after topical application to rats. Mar. Drugs 2019, 17, 687.
  50. Corino, C.; Di Giancamillo, A.; Modina, S.C.; Rossi, R. Prebiotic effects of seaweed polysaccharides in pigs. Animals 2021, 11, 1573.
  51. Shikov, A.N.; Flisyuk, E.V.; Obluchinskaya, E.D.; Pozharitskaya, O.N. Pharmacokinetics of marine-derived drugs. Mar. Drugs 2020, 18, 557.
  52. Mohammed, A.S.A.; Naveed, M.; Jost, N. Polysaccharides; classification, chemical properties, and future perspective applications in fields of pharmacology and biological medicine (A review of current applications and upcoming potentialities). J. Polym. Environ. 2021.
  53. Rasmussen, R.S.; Morrissey, M.T. Marine Biotechnology for Production of Food Ingredients. In Advances in Food and Nutrition Research; Academic Press: Cambridge, MA, USA, 2007; Volume 52, pp. 237–292.
  54. Peñalver, R.; Lorenzo, J.M.; Ros, G.; Amarowicz, R.; Pateiro, M.; Nieto, G. Seaweeds as a functional ingredient for a healthy diet. Mar. Drugs 2020, 18, 301.
  55. Wong, K.H.; Cheung, P.C.K. Nutritional evaluation of some subtropical red and green seaweeds: Part I—Proximate composition, amino acid profiles and some physico-chemical properties. Food Chem. 2000, 71, 475–482.
  56. Cherry, P.; O’Hara, C.; Magee, P.J.; McSorley, E.M.; Allsopp, P.J. Risks and benefits of consuming edible seaweeds. Nutr. Rev. 2019, 77, 307–329.
  57. Kraan, S. Chapter 22-Algal polysaccharides, novel applications and outlook. In Carbohydrates-Comprehensive Studies on Glycobiology and Glycotechnology; Chang, C.F., Ed.; IntechOpen: Rijeka, Croatia, 2012.
  58. de Jesus Raposo, M.F.; de Morais, A.M.; de Morais, R.M. Emergent sources of prebiotics: Seaweeds and microalgae. Mar. Drugs 2016, 14, 27.
  59. Sanz-Pintos, N.; Pérez-Jiménez, J.; Buschmann, A.H.; Vergara-Salinas, J.R.; Pérez-Correa, J.R.; Saura-Calixto, F. Macromolecular antioxidants and dietary fiber in edible seaweeds. J. Food Sci. 2017, 82, 289–295.
  60. Fernando, I.P.S.; Kim, K.-N.; Kim, D.; Jeon, Y.-J. Algal polysaccharides: Potential bioactive substances for cosmeceutical applications. Crit. Rev. Biotechnol. 2019, 39, 99–113.
  61. Olsson, J.; Toth, G.B.; Albers, E. Biochemical composition of red, green and brown seaweeds on the Swedish west coast. J. Appl. Phycol. 2020.
  62. Tannock, G.W.; Liu, Y. Guided dietary fibre intake as a means of directing short-chain fatty acid production by the gut microbiota. J. R. Soc. N. Z. 2020, 50, 434–455.
  63. Hjorth, M.F.; Astrup, A. The role of viscous fiber for weight loss: Food for thought and gut bacteria. Am. J. Clin. Nutr. 2020.
  64. Bindels, L.B.; Delzenne, N.M.; Cani, P.D.; Walter, J. Towards a more comprehensive concept for prebiotics. Nat. Rev. Gastroenterol. Hepatol. 2015, 12, 303–310.
  65. Li, M.; Shang, Q.; Li, G.; Wang, X.; Yu, G. Degradation of marine algae-derived carbohydrates by Bacteroidetes isolated from human gut microbiota. Mar. Drugs 2017, 15, 92.
  66. Tamura, K.; Hemsworth, G.R.; Déjean, G.; Rogers, T.E.; Pudlo, N.A.; Urs, K.; Jain, N.; Davies, G.J.; Martens, E.C.; Brumer, H. Molecular mechanism by which prominent human gut bacteroidetes utilize mixed-linkage beta-glucans, major health-promoting cereal polysaccharides. Cell Rep. 2017, 21, 417–430.
  67. Salyers, A.A.; Vercellotti, J.R.; West, S.E.; Wilkins, T.D. Fermentation of mucin and plant polysaccharides by strains of Bacteroides from the human colon. Appl. Environ. Microbiol. 1977, 33, 319–322. Available online: (accessed on 11 August 2020).
  68. Becker, S.; Tebben, J.; Coffinet, S.; Wiltshire, K.; Iversen, M.H.; Harder, T.; Hinrichs, K.-U.; Hehemann, J.-H. Laminarin is a major molecule in the marine carbon cycle. Proc. Natl. Acad. Sci. USA 2020, 117, 6599–6607.
  69. Zaharudin, N.; Tullin, M.; Pekmez, C.T.; Sloth, J.J.; Rasmussen, R.R.; Dragsted, L.O. Effects of brown seaweeds on postprandial glucose, insulin and appetite in humans–A randomized, 3-way, blinded, cross-over meal study. Clin. Nutr. 2020.
  70. Hui, Y.; Tamez-Hidalgo, P.; Cieplak, T.; Satessa, G.D.; Kot, W.; Søren, S.K.; Nielsen, M.O.; Nielsen, D.S.; Krych, L. Supplementation of a lacto-fermented rapeseed-seaweed blend promotes gut microbial- and gut immune-modulation in weaner piglets. bioRxiv 2020, 2020.09.22.308106.
  71. Chen, L.; Xu, W.; Chen, D.; Chen, G.; Liu, J.; Zeng, X.; Shao, R.; Zhu, H. Digestibility of sulfated polysaccharide from the brown seaweed Ascophyllum nodosum and its effect on the human gut microbiota in vitro. Int. J. Biol. Macromol. 2018, 112, 1055–1061.
  72. You, L.; Gong, Y.; Li, L.; Hu, X.; Brennan, C.; Kulikouskaya, V. Beneficial effects of three brown seaweed polysaccharides on gut microbiota and their structural characteristics: An overview. Int. J. Food Sci. Tech. 2020, 55, 1199–1206.
  73. de Borba Gurpilhares, D.; Cinelli, L.P.; Simas, N.K.; Pessoa, A., Jr.; Sette, L.D. Marine prebiotics: Polysaccharides and oligosaccharides obtained by using microbial enzymes. Food Chem. 2019, 280, 175–186.
  74. Garcia-Vaquero, M.; Rajauria, G.; O’Doherty, J.V.; Sweeney, T. Polysaccharides from macroalgae: Recent advances, innovative technologies and challenges in extraction and purification. Food Res. Int. 2017, 99, 1011–1020.
  75. Usov, A.; Zelinsky, N. Chapter 2-Chemical structures of algal polysaccharides. In Functional Ingredients from Algae for Foods and Nutraceuticals; Domínguez, H., Ed.; Woodhead Publishing: Cambridge, UK, 2013; pp. 23–86.
  76. Tanna, B.; Mishra, A. Nutraceutical potential of seaweed polysaccharides: Structure, bioactivity, safety, and toxicity. Compr. Rev. Food Sci. Food Saf. 2019, 18, 817–831.
  77. Koh, H.S.A.; Lu, J.; Zhou, W. Structure characterization and antioxidant activity of fucoidan isolated from Undaria pinnatifida grown in New Zealand. Carbohydr. Polym. 2019, 212, 178–185.
  78. Deniaud-Bouët, E.; Hardouin, K.; Potin, P.; Kloareg, B.; Hervé, C. A review about brown algal cell walls and fucose-containing sulfated polysaccharides: Cell wall context, biomedical properties and key research challenges. Carbohydr. Polym. 2017, 175, 395–408.
  79. Skriptsova, A.V. Fucoidans of brown algae: Biosynthesis, localization, and physiological role in thallus. Russ. J. Mar. Biol. 2015, 41, 145–156.
  80. Usoltseva, R.V.; Anastyuk, S.D.; Surits, V.V.; Shevchenko, N.M.; Thinh, P.D.; Zadorozhny, P.A.; Ermakova, S.P. Comparison of structure and in vitro anticancer activity of native and modified fucoidans from Sargassum feldmannii and S. duplicatum. Int. J. Biol. Macromol. 2019, 124, 220–228.
  81. Elizondo-Gonzalez, R.; Cruz-Suarez, L.E.; Ricque-Marie, D.; Mendoza-Gamboa, E.; Rodriguez-Padilla, C.; Trejo-Avila, L.M. In vitro characterization of the antiviral activity of fucoidan from Cladosiphon okamuranus against Newcastle Disease Virus. Virol. J. 2012, 9, 307.
  82. Hwang, P.A.; Phan, N.N.; Lu, W.J.; Ngoc Hieu, B.T.; Lin, Y.C. Low-molecular-weight fucoidan and high-stability fucoxanthin from brown seaweed exert prebiotics and anti-inflammatory activities in Caco-2 cells. Food Nutr. Res. 2016, 60.
  83. Irhimeh, M.R.; Fitton, J.H.; Lowenthal, R.M. Pilot clinical study to evaluate the anticoagulant activity of fucoidan. Blood Coagul. Fibrinolysis 2009, 20, 607–610.
  84. Tsai, H.-L.; Tai, C.-J.; Huang, C.-W.; Chang, F.-R.; Wang, J.-Y. Efficacy of low-molecular-weight fucoidan as a supplemental therapy in metastatic colorectal cancer patients: A double-blind randomized controlled trial. Mar. Drugs 2017, 15, 122.
  85. Maruyama, H.; Tamauchi, H.; Hashimoto, M.; Nakano, T. Antitumor activity and immune response of Mekabu fucoidan extracted from sporophyll of Undaria pinnatifida. In Vivo 2003, 17, 245–249. Available online: (accessed on 19 May 2020).
  86. Lin, H.-T.V.; Tsou, Y.-C.; Chen, Y.-T.; Lu, W.-J.; Hwang, P.-A. Effects of low-molecular-weight fucoidan and high stability fucoxanthin on glucose homeostasis, lipid metabolism, and liver function in a mouse model of type II diabetes. Mar. Drugs 2017, 15, 113.
  87. Okolie, C.L.; Mason, B.; Mohan, A.; Pitts, N.; Udenigwe, C.C. The comparative influence of novel extraction technologies on in vitro prebiotic-inducing chemical properties of fucoidan extracts from Ascophyllum nodosum. Food Hydrocoll. 2019, 90, 462–471.
  88. Kan, J.; Cheng, J.; Xu, L.; Hood, M.; Zhong, D.; Cheng, M.; Liu, Y.; Chen, L.; Du, J. The combination of wheat peptides and fucoidan protects against chronic superficial gastritis and alters gut microbiota: A double-blinded, placebo-controlled study. Eur. J. Nutr. 2020, 59, 1655–1666.
  89. Takahashi, M.; Takahashi, K.; Abe, S.; Yamada, K.; Suzuki, M.; Masahisa, M.; Endo, M.; Abe, K.; Inoue, R.; Hoshi, H. Improvement of psoriasis by alteration of the gut environment by oral administration of fucoidan from Cladosiphon okamuranus. Mar. Drugs 2020, 18, 154.
  90. Parnell, J.A.; Reimer, R.A. Prebiotic fiber modulation of the gut microbiota improves risk factors for obesity and the metabolic syndrome. Gut Microbes 2012, 3, 29–34.
  91. Zhang, X.; Liu, Y.; Chen, X.-Q.; Aweya, J.J.; Cheong, K.-L. Catabolism of Saccharina japonica polysaccharides and oligosaccharides by human fecal microbiota. LWT 2020, 130, 109635.
  92. Shang, Q.; Shan, X.; Cai, C.; Hao, J.; Li, G.; Yu, G. Dietary fucoidan modulates the gut microbiota in mice by increasing the abundance of Lactobacillus and Ruminococcaceae. Food Funct. 2016, 7, 3224–3232.
  93. Olatunji, O. Aquatic Biopolymers: Understanding Their Industrial Significance and Environmental Implications; Springer Nature: Cham, Switzerland, 2020.
  94. Baweja, P.; Sahoo, D. Chapter 2-Classification of algae. In The Algae World; Sahoo, D., Seckbach, J., Eds.; Springer: Dordrecht, The Netherlands, 2015; pp. 31–55.
  95. Usman, A.; Khalid, S.; Usman, A.; Hussain, Z.; Wang, Y. Chapter 5-Algal polysaccharides, novel application, and outlook. In Algae Based Polymers, Blends, and Composites; Zia, K.M., Zuber, M., Ali, M., Eds.; Elsevier: Amsterdam, The Netherlands, 2017; pp. 115–153.
  96. Kadam, S.U.; O’Donnell, C.P.; Rai, D.K.; Hossain, M.B.; Burgess, C.M.; Walsh, D.; Tiwari, B.K. Laminarin from Irish brown seaweeds Ascophyllum nodosum and Laminaria hyperborea: Ultrasound assisted extraction, characterization and bioactivity. Mar. Drugs 2015, 13, 4270–4280.
  97. Song, K.; Xu, L.; Zhang, W.; Cai, Y.; Jang, B.; Oh, J.; Jin, J.O. Laminarin promotes anti-cancer immunity by the maturation of dendritic cells. Oncotarget 2017, 8, 38554–38567.
  98. Miao, H.-Q.; Elkin, M.; Aingorn, E.; Ishai-Michaeli, R.; Stein, C.A.; Vlodavsky, I. Inhibition of heparanase activity and tumor metastasis by laminarin sulfate and synthetic phosphorothioate oligodeoxynucleotides. Int. J. Cancer 1999, 83, 424–431.
  99. Cuong, D.X. Laminarin (beta-glucan) of brown algae Sargassum mcclurei: Extraction, antioxidant activity, lipoxygenase inhibition activity, and physicochemistry properties. World J. Food Sci. Technol. 2020, 4, 31.
  100. Lee, J.; Kim, Y.-J.; Kim, H.; Kim, Y.-S.; Park, W. Immunostimulatory effect of laminarin on RAW 264.7 mouse macrophages. Molecules 2012, 17, 5404–5411.
  101. Leonard, S.; Sweeney, T.; Bahar, B.; O’Doherty, J. Effect of maternal seaweed extract supplementation on suckling piglet growth, humoral immunity, selected microflora, and immune response after an ex vivo lipopolysaccharide challenge. J. Anim. Sci. 2012, 90, 505–514.
  102. Vigors, S.; O’Doherty, J.V.; Rattigan, R.; McDonnell, M.J.; Rajauria, G.; Sweeney, T. Effect of a laminarin rich macroalgal extract on the caecal and colonic microbiota in the post-weaned pig. Mar. Drugs 2020, 18, 157.
  103. Rattigan, R.; Sweeney, T.; Maher, S.; Thornton, K.; Rajauria, G.; O’Doherty, J.V. Laminarin-rich extract improves growth performance, small intestinal morphology, gene expression of nutrient transporters and the large intestinal microbial composition of piglets during the critical post-weaning period. Br. J. Nutr. 2019, 123, 255–263.
  104. Lynch, M.B.; Sweeney, T.; Callan, J.J.; O’Sullivan, J.T.; O’Doherty, J.V. The effect of dietary Laminaria-derived laminarin and fucoidan on nutrient digestibility, nitrogen utilisation, intestinal microflora and volatile fatty acid concentration in pigs. J. Sci. Food Agric. 2010, 90, 430–437.
  105. Zhang, Y.; Zhao, N.; Yang, L.; Hong, Z.; Cai, B.; Le, Q.; Yang, T.; Shi, L.; He, J.; Cui, C.-B. Insoluble dietary fiber derived from brown seaweed Laminaria japonica ameliorate obesity-related features via modulating gut microbiota dysbiosis in high-fat diet-fed mice. Food Funct. 2020.
  106. O’Sullivan, L.; Murphy, B.; McLoughlin, P.; Duggan, P.; Lawlor, P.G.; Hughes, H.; Gardiner, G.E. Prebiotics from marine macroalgae for human and animal health applications. Mar. Drugs 2010, 8, 2038–2064.
  107. Pereira, L.; Cotas, J. Chapter 1-Introductory chapter: Alginates-a general overview. In Alginates-Recent Uses of This Natural Polymer; Pereira, L., Ed.; IntechOpen: Rijeka, Croatia, 2020.
  108. Mei, X.; Chang, Y.; Shen, J.; Zhang, Y.; Xue, C. Expression and characterization of a novel alginate-binding protein: A promising tool for investigating alginate. Carbohydr. Polym. 2020, 246, 116645.
  109. Ramos, P.E.; Silva, P.; Alario, M.M.; Pastrana, L.M.; Teixeira, J.A.; Cerqueira, M.A.; Vicente, A.A. Effect of alginate molecular weight and M/G ratio in beads properties foreseeing the protection of probiotics. Food Hydrocoll. 2018, 77, 8–16.
  110. Mancini, F.; Montanari, L.; Peressini, D.; Fantozzi, P. Influence of alginate concentration and molecular weight on functional properties of mayonnaise. LWT 2002, 35, 517–525.
  111. Jönsson, M.; Allahgholi, L.; Sardari, R.R.; Hreggviðsson, G.O.; Nordberg Karlsson, E. Extraction and modification of macroalgal polysaccharides for current and next-generation applications. Molecules 2020, 25, 930.
  112. Bai, S.; Chen, H.; Zhu, L.; Liu, W.; Yu, H.D.; Wang, X.; Yin, Y. Comparative study on the in vitro effects of Pseudomonas aeruginosa and seaweed alginates on human gut microbiota. PLoS ONE 2017, 12, e0171576.
  113. Li, M.; Li, G.; Shang, Q.; Chen, X.; Liu, W.; Pi, X.; Zhu, L.; Yin, Y.; Yu, G.; Wang, X. In vitro fermentation of alginate and its derivatives by human gut microbiota. Anaerobe 2016, 39, 19–25.
  114. Mizuno, H.; Bamba, S.; Abe, N.; Sasaki, M. Effects of an alginate-containing variable-viscosity enteral nutrition formula on defecation, intestinal microbiota, and short-chain fatty acid production. J. Funct. Foods 2020, 67, 103852.
  115. Georg-Jensen, M.; Pedersen, C.; Kristensen, M.; Frost, G.; Astrup, A. Efficacy of alginate supplementation in relation to appetite regulation and metabolic risk factors: Evidence from animal and human studies. Obes. Rev. 2013, 14, 129–144.
  116. Guo, L.; Goff, H.D.; Xu, F.; Liu, F.; Ma, J.; Chen, M.; Zhong, F. The effect of sodium alginate on nutrient digestion and metabolic responses during both in vitro and in vivo digestion process. Food Hydrocoll. 2020, 107, 105304.
  117. Hu, Y.; Feng, Z.; Feng, W.; Hu, T.; Guan, H.; Mao, Y. AOS ameliorates monocrotaline-induced pulmonary hypertension by restraining the activation of P-selectin/p38MAPK/NF-κB pathway in rats. Biomed. Pharmacother. 2019, 109, 1319–1326.
  118. Amimi, A.; Mouradi, A.; Bennasser, L.; Givernaud, T. Seasonal variations in thalli and carrageenan composition of Gigartina pistillata (Gmelin) Stackhouse (Rhodophyta, Gigartinales) harvested along the Atlantic coast of Morocco. Phycol. Res. 2007, 55, 143–149.
  119. Jiao, G.; Yu, G.; Zhang, J.; Ewart, H.S. Chemical structures and bioactivities of sulfated polysaccharides from marine algae. Mar. Drugs 2011, 9, 196–223.
  120. Oladzadabbasabadi, N.; Ebadi, S.; Nafchi, A.M.; Karim, A.; Kiahosseini, S.R. Functional properties of dually modified sago starch/κ-carrageenan films: An alternative to gelatin in pharmaceutical capsules. Carbohydr. Polym. 2017, 160, 43–51.
  121. McKim, J.; Willoughby, J.; Blakemore, W.; Weiner, M. Clarifying the confusion between poligeenan, degraded carrageenan, and carrageenan: A review of the chemistry, nomenclature, and in vivo toxicology by the oral route. Crit. Rev. Food Sci. Nutr. 2018, 59, 1–70.
  122. Uno, Y.; Omoto, T.; Goto, Y.; Asai, I.; Nakamura, M.; Maitani, T. Molecular weight distribution of carrageenans studied by a combined gel permeation/inductively coupled plasma (GPC/ICP) method. Food Addit. Contam. 2001, 18, 763–772.
  123. Du Preez, R.; Paul, N.; Mouatt, P.; Majzoub, M.E.; Thomas, T.; Panchal, S.K.; Brown, L. Carrageenans from the red seaweed Sarconema filiforme attenuate symptoms of diet-induced metabolic syndrome in rats. Mar. Drugs 2020, 18, 97.
  124. Sun, Y.; Cui, X.; Duan, M.; Ai, C.; Song, S.; Chen, X. In vitro fermentation of κ-carrageenan oligosaccharides by human gut microbiota and its inflammatory effect on HT29 cells. J. Func. Foods 2019, 59, 80–91.
  125. Isaka, S.; Cho, K.; Nakazono, S.; Abu, R.; Ueno, M.; Kim, D.; Oda, T. Antioxidant and anti-inflammatory activities of porphyran isolated from discolored nori (Porphyra yezoensis). Int. J. Biol. Macromol. 2015, 74, 68–75.
  126. Xu, S.-Y.; Aweya, J.J.; Li, N.; Deng, R.-Y.; Chen, W.-Y.; Tang, J.; Cheong, K.-L. Microbial catabolism of Porphyra haitanensis polysaccharides by human gut microbiota. Food Chem. 2019, 289, 177–186.
  127. Qiu, H.-M.; Veeraperumal, S.; Lv, J.-H.; Wu, T.-C.; Zhang, Z.-P.; Zeng, Q.-K.; Liu, Y.; Chen, X.-Q.; Aweya, J.J.; Cheong, K.-L. Physicochemical properties and potential beneficial effects of porphyran from Porphyra haitanensis on intestinal epithelial cells. Carbohydr. Polym. 2020, 246, 116626.
  128. Zhao, T.; Zhang, Q.; Qi, H.; Zhang, H.; Niu, X.; Xu, Z.; Li, Z. Degradation of porphyran from Porphyra haitanensis and the antioxidant activities of the degraded porphyrans with different molecular weight. Int. J. Biol. Macromol. 2006, 38, 45–50.
  129. Bhatia, S.; Sharma, A.; Sharma, K.; Kavale, M.; Chaugule, B.; Dhalwal, K.; Namdeo, A.; Mahadik, K. Novel algal polysaccharides from marine source: Porphyran. Pharmacogn. Rev. 2008, 2, 271. Available online: (accessed on 8 June 2020).
  130. He, D.; Wu, S.; Yan, L.; Zuo, J.; Cheng, Y.; Wang, H.; Liu, J.; Zhang, X.; Wu, M.; Choi, J.-I.; et al. Antitumor bioactivity of porphyran extracted from Pyropia yezoensis Chonsoo2 on human cancer cell lines. J. Sci. Food Agric. 2019, 99, 6722–6730.
  131. Kwon, M.-J.; Nam, T.-J. Chromatographically purified porphyran from Porphyra yezoensis effectively inhibits proliferation of human cancer cells. Food Sci. Biotechnol. 2007, 16, 873–878. Available online: (accessed on 13 July 2020).
  132. Seong, H.; Bae, J.-H.; Seo, J.S.; Kim, S.-A.; Kim, T.-J.; Han, N.S. Comparative analysis of prebiotic effects of seaweed polysaccharides laminaran, porphyran, and ulvan using in vitro human fecal fermentation. J. Funct. Foods 2019, 57, 408–416.
  133. Xu, S.-Y.; Chen, X.-Q.; Liu, Y.; Cheong, K.-L. Ultrasonic/microwave-assisted extraction, simulated digestion, and fermentation in vitro by human intestinal flora of polysaccharides from Porphyra haitanensis. Int. J. Biol. Macromol. 2020, 152, 748–756.
  134. Kulshreshtha, G.; Rathgeber, B.; Stratton, G.; Thomas, N.; Evans, F.; Critchley, A.; Hafting, J.; Prithiviraj, B. Feed supplementation with red seaweeds, Chondrus crispus and Sarcodiotheca gaudichaudii, affects performance, egg quality, and gut microbiota of layer hens. Poult. Sci. 2014, 93, 2991–3001.
  135. Liu, J.; Kandasamy, S.; Zhang, J.; Kirby, C.W.; Karakach, T.; Hafting, J.; Critchley, A.T.; Evans, F.; Prithiviraj, B. Prebiotic effects of diet supplemented with the cultivated red seaweed Chondrus crispus or with fructo-oligo-saccharide on host immunity, colonic microbiota and gut microbial metabolites. BMC Complement. Altern. Med. 2015, 15, 279.
  136. Balasubramanian, B.; Shanmugam, S.; Park, S.; Recharla, N.; Koo, J.S.; Andretta, I.; Kim, I.H. Supplemental impact of marine red seaweed (Halymenia palmata) on the growth performance, total tract nutrient digestibility, blood profiles, intestine histomorphology, meat quality, fecal gas emission, and microbial counts in broilers. Animals 2021, 11, 1244.
  137. Lahaye, M. NMR spectroscopic characterisation of oligosaccharides from two Ulva rigida ulvan samples (Ulvales, Chlorophyta) degraded by a lyase. Carbohydr. Res. 1998, 314, 1–12.
  138. Michel, G.; Czjzek, M. Chapter 16-Polysaccharide-degrading enzymes from marine bacteria. In Marine Enzymes for Biocatalysis: Sources, Biocatalytic Characteristics and Bioprocesses of Marine Enzymes; Trincone, A., Ed.; Woodhead Publishing: Cambridge, UK, 2013; pp. 429–464.
  139. Kidgell, J.T.; Magnusson, M.; de Nys, R.; Glasson, C.R.K. Ulvan: A systematic review of extraction, composition and function. Algal Res. 2019, 39, 101422.
  140. Adrien, A.; Bonnet, A.; Dufour, D.; Baudouin, S.; Maugard, T.; Bridiau, N. Anticoagulant activity of sulfated ulvan isolated from the green macroalga Ulva rigida. Mar. Drugs 2019, 17, 291.
  141. Klongklaew, N.; Praiboon, J.; Tamtin, M.; Srisapoome, P. Antibacterial and antiviral activities of local Thai green macroalgae crude extracts in pacific white shrimp (Litopenaeus vannamei). Mar. Drugs 2020, 18, 140.
  142. Chi, Y.; Zhang, M.; Wang, X.; Fu, X.; Guan, H.; Wang, P. Ulvan lyase assisted structural characterization of ulvan from Ulva pertusa and its antiviral activity against vesicular stomatitis virus. Int. J. Biol. Macromol. 2020, 157, 75–82.
  143. Berri, M.; Olivier, M.; Holbert, S.; Dupont, J.; Demais, H.; Le Goff, M.; Collen, P.N. Ulvan from Ulva armoricana (Chlorophyta) activates the PI3K/Akt signalling pathway via TLR4 to induce intestinal cytokine production. Algal Res. 2017, 28, 39–47.
  144. Cañedo-Castro, B.; Piñón-Gimate, A.; Carrillo, S.; Ramos, D.; Casas-Valdez, M. Prebiotic effect of Ulva rigida meal on the intestinal integrity and serum cholesterol and triglyceride content in broilers. J. Appl. Phycol. 2019, 31, 3265–3273.
  145. Shalaby, M.; Amin, H. Potential using of ulvan polysaccharides from Ulva lactuca as a prebiotic in symbiotic yogurt production. J. Probiot. Health 2019, 7, 1–9.
  146. Kong, Q.; Dong, S.; Gao, J.; Jiang, C. In vitro fermentation of sulfated polysaccharides from E. prolifera and L. japonica by human fecal microbiota. Int. J. Biol. Macromol. 2016, 91, 867–871.
  147. Strain, C.R.; Collins, K.C.; Naughton, V.; McSorley, E.M.; Stanton, C.; Smyth, T.J.; Soler-Vila, A.; Rea, M.C.; Ross, P.R.; Cherry, P.; et al. Effects of a polysaccharide-rich extract derived from Irish-sourced Laminaria digitata on the composition and metabolic activity of the human gut microbiota using an in vitro colonic model. Eur. J. Nutr. 2020, 59, 309–325.
  148. Charoensiddhi, S.; Conlon, M.A.; Vuaran, M.S.; Franco, C.M.M.; Zhang, W. Impact of extraction processes on prebiotic potential of the brown seaweed Ecklonia radiata by in vitro human gut bacteria fermentation. J. Funct. Foods 2016, 24, 221–230.
  149. Charoensiddhi, S.; Conlon, M.A.; Methacanon, P.; Franco, C.M.M.; Su, P.; Zhang, W. Gut health benefits of brown seaweed Ecklonia radiata and its polysaccharides demonstrated in vivo in a rat model. J. Funct. Foods 2017, 37, 676–684.
  150. Wang, Y.; Chen, G.; Peng, Y.; Rui, Y.; Zeng, X.; Ye, H. Simulated digestion and fermentation in vitro with human gut microbiota of polysaccharides from Coralline pilulifera. LWT 2019, 100, 167–174.
  151. Cui, M.; Zhou, R.; Wang, Y.; Zhang, M.; Liu, K.; Ma, C. Beneficial effects of sulfated polysaccharides from the red seaweed Gelidium pacificum Okamura on mice with antibiotic-associated diarrhea. Food Funct. 2020, 11, 4625–4637.
  152. Sun, L.; Warren, F.J.; Gidley, M.J. Natural products for glycaemic control: Polyphenols as inhibitors of alpha-amylase. Trends Food Sci. Technol. 2019, 91, 262–273.
  153. Mannino, A.M.; Micheli, C. Ecological function of phenolic compounds from Mediterranean fucoid algae and seagrasses: An overview on the genus Cystoseira sensu lato and Posidonia oceanica (L.) Delile. J. Mar. Sci. Eng. 2020, 8, 19.
  154. Holdt, S.L.; Kraan, S. Bioactive compounds in seaweed: Functional food applications and legislation. J. Appl. Phycol. 2011, 23, 543–598.
  155. Poole, J.; Diop, A.; Rainville, L.C.; Barnabé, S. Bioextracting polyphenols from the brown seaweed Ascophyllum nodosum from Québec’s north shore coastline. Ind. Biotechnol. 2019, 15, 212–218.
  156. Wekre, M.E.; Kåsin, K.; Underhaug, J.; Holmelid, B.; Jordheim, M. Quantification of polyphenols in seaweeds: A case study of Ulva intestinalis. Antioxidants 2019, 8, 612.
  157. Quideau, S.; Deffieux, D.; Douat-Casassus, C.; Pouységu, L. Plant polyphenols: Chemical properties, biological activities, and synthesis. Angew. Chem. Int. Ed. 2011, 50, 586–621.
  158. Freile-Pelegrin, Y.; Robledo, D. Chapter 6-Bioactive phenolic compounds from algae. In Bioactive Compounds from Marine Foods: Plant and Animal Sources; Hernández-Ledesma, B., Herrero, M., Eds.; Wiley-Blackwell: Chichester, UK, 2014; pp. 113–129.
  159. Murray, M.; Dordevic, A.L.; Cox, K.; Scholey, A.; Ryan, L.; Bonham, M.P. Twelve weeks’ treatment with a polyphenol-rich seaweed extract increased HDL cholesterol with no change in other biomarkers of chronic disease risk in overweight adults: A placebo-controlled randomised trial. J. Nutr. Biochem. 2021, 108777.
  160. Haskell-Ramsay, C.F.; Jackson, P.A.; Dodd, F.L.; Forster, J.S.; Bérubé, J.; Levinton, C.; Kennedy, D.O. Acute post-prandial cognitive effects of brown seaweed extract in humans. Nutrients 2018, 10, 85.
  161. Hata, Y.; Nakajima, K.; Uchida, J.-I.; Hidaka, H.; Nakano, T. Clinical effects of brown seaweed, Undaria pinnatifida (wakame), on blood pressure in hypertensive subjects. J. Clin. Biochem. Nutr. 2001, 30, 43–53.
  162. Derosa, G.; Pascuzzo, M.D.; D’Angelo, A.; Maffioli, P. Ascophyllum nodosum, Fucus vesiculosus and chromium picolinate nutraceutical composition can help to treat type 2 diabetic patients. Diabetes. Metab. Syndr. Obes. 2019, 12, 1861–1865.
  163. Murray, M.; Dordevic, A.L.; Ryan, L.; Bonham, M.P. A single-dose of a polyphenol-rich Fucus vesiculosus extract is insufficient to blunt the elevated postprandial blood glucose responses exhibited by healthy adults in the evening: A randomised crossover trial. Antioxidants 2019, 8, 49.
  164. Cardona, F.; Andrés-Lacueva, C.; Tulipani, S.; Tinahones, F.J.; Queipo-Ortuño, M.I. Benefits of polyphenols on gut microbiota and implications in human health. J. Nutr. Biochem. 2013, 24, 1415–1422.
  165. Tomás-Barberán, F.A.; Selma, M.V.; Espín, J.C. Interactions of gut microbiota with dietary polyphenols and consequences to human health. Curr. Opin. Clin. Nutr. Metab. Care 2016, 19, 471–476.
  166. Kumar Singh, A.; Cabral, C.; Kumar, R.; Ganguly, R.; Kumar Rana, H.; Gupta, A.; Rosaria Lauro, M.; Carbone, C.; Reis, F.; Pandey, A.K. Beneficial effects of dietary polyphenols on gut microbiota and strategies to improve delivery efficiency. Nutrients 2019, 11, 2216.
  167. Stevens, J.F.; Maier, C.S. The chemistry of gut microbial metabolism of polyphenols. Phytochem. Rev. 2016, 15, 425–444.
  168. Selma, M.V.; Espin, J.C.; Tomas-Barberan, F.A. Interaction between phenolics and gut microbiota: Role in human health. J. Agric. Food. Chem. 2009, 57, 6485–6501.
  169. Samanta, A.; Das, G.; Das, S.K. Roles of flavonoids in plants. Int. J. Pharm. Sci. Tech. 2011, 6, 12–35. Available online: (accessed on 27 July 2020).
  170. Lin, G.; Liu, X.; Yan, X.; Liu, D.; Yang, C.; Liu, B.; Huang, Y.; Zhao, C. Role of green macroalgae Enteromorpha prolifera polyphenols in the modulation of gene expression and intestinal microflora profiles in type 2 diabetic mice. Int. J. Mol. Sci. 2019, 20, 25.
  171. Yoshie-Stark, Y.; Hsieh, Y.-P.; Suzuki, T. Distribution of flavonoids and related compounds from seaweeds in Japan. J. Tokyo Univ. Fish. 2003, 89, 1–6. Available online: (accessed on 3 July 2020).
  172. Culioli, G.; Ortalo-Magné, A.; Valls, R.; Hellio, C.; Clare, A.S.; Piovetti, L. Antifouling activity of meroditerpenoids from the marine brown alga Halidrys siliquosa. J. Nat. Prod. 2008, 71, 1121–1126.
  173. Gómez-Guzmán, M.; Rodríguez-Nogales, A.; Algieri, F.; Gálvez, J. Potential role of seaweed polyphenols in cardiovascular-associated disorders. Mar. Drugs 2018, 16, 250.
  174. Dong, H.; Dong, S.; Erik Hansen, P.; Stagos, D.; Lin, X.; Liu, M. Progress of bromophenols in marine algae from 2011 to 2020: Structure, bioactivities, and applications. Mar. Drugs 2020, 18, 411.
  175. Shibata, T.; Miyasaki, T.; Miyake, H.; Tanaka, R.; Kawaguchi, S. The influence of phlorotannins and bromophenols on the feeding behavior of marine herbivorous gastropod Turbo cornutus. Am. J. Plant Sci. 2014, 5, 387–392.
  176. Nielsen, B.V.; Maneein, S.; Farid, A.; Mahmud, M.; Milledge, J.J. The effects of halogenated compounds on the anaerobic digestion of macroalgae. Fermentation 2020, 6, 85.
  177. Hay, M.E.; Fenical, W. Marine plant-herbivore interactions: The ecology of chemical defense. Annu. Rev. Ecol. Syst. 1988, 19, 111–145.
  178. Whitfield, F.; Helidoniotis, F.; Drew, M. Effect of Diet and Environment on the Volatile Flavour Components of Crustaceans; CSIRO and Fisheries Research & Development Corporation: North Ryde, NSW, Australia, 1995. Available online: (accessed on 8 June 2020).
  179. Whitfield, F.B.; Helidoniotis, F.; Shaw, K.J.; Svoronos, D. Distribution of bromophenols in species of marine algae from eastern Australia. J. Agric. Food. Chem. 1999, 47, 2367–2373.
  180. Luo, J.; Xu, Q.; Jiang, B.; Zhang, R.; Jia, X.; Li, X.; Wang, L.; Guo, C.; Wu, N.; Shi, D. Selectivity, cell permeability and oral availability studies of novel bromophenol derivative HPN as protein tyrosine phosphatase 1B inhibitor. Br. J. Pharmacol. 2018, 175, 140–153.
  181. Zhang, Y.; Glukhov, E.; Yu, H.; Gerwick, L.; Dorrestein, P.; Gerwick, W. Monomeric and dimeric bromophenols from the red alga Ceramium sp. with antioxidant and anti-inflammatory activities. ChemRxiv 2020.
  182. Cherian, C.; Vennila, J.J.; Sharan, L. Marine bromophenols as an effective inhibitor of virulent proteins (peptidyl arginine deiminase, gingipain R and hemagglutinin A) in Porphyromas gingivalis. Arch. Oral Biol. 2019, 100, 119–128.
  183. Shi, D.; Li, J.; Guo, S.; Su, H.; Fan, X. The antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo. Chin. J. Oceanol. Limnol. 2009, 27, 277–282.
  184. Shi, D.; Li, X.; Li, J.; Guo, S.; Su, H.; Fan, X. Antithrombotic effects of bromophenol, an alga-derived thrombin inhibitor. Chin. J. Oceanol. Limnol. 2010, 28, 96–98.
  185. Nguyen, T.H.; Nguyen, T.L.P.; Tran, T.V.A.; Do, A.D.; Kim, S.M. Antidiabetic and antioxidant activities of red seaweed Laurencia dendroidea. Asian Pac. J. Trop. Biomed. 2019, 9, 501.
  186. Wang, C.; Jiang, D.; Sun, Y.; Gu, Y.; Ming, Y.; Zheng, J.; Yu, C.; Chen, X.; Qi, H. Synergistic effects of UVA irradiation and phlorotannin extracts of Laminaria japonica on properties of grass carp myofibrillar protein gel. J. Sci. Food Agric. 2020.
  187. Lemesheva, V.; Birkemeyer, C.; Garbary, D.; Tarakhovskaya, E. Vanadium-dependent haloperoxidase activity and phlorotannin incorporation into the cell wall during early embryogenesis of Fucus vesiculosus (Phaeophyceae). Eur. J. Phycol. 2020, 55, 275–284.
  188. Gómez, I.; Huovinen, P. Induction of phlorotannins during UV exposure mitigates inhibition of photosynthesis and DNA damage in the kelp Lessonia nigrescens. Photochem. Photobiol. 2010, 86, 1056–1063.
  189. Arnold, T.M.; Targett, N.M. To grow and defend: Lack of tradeoffs for brown algal phlorotannins. Oikos 2003, 100, 406–408.
  190. Lopes, G.; Barbosa, M.; Vallejo, F.; Gil-Izquierdo, Á.; Andrade, P.B.; Valentão, P.; Pereira, D.M.; Ferreres, F. Profiling phlorotannins from Fucus spp. of the Northern Portuguese coastline: Chemical approach by HPLC-DAD-ESI/MSn and UPLC-ESI-QTOF/MS. Algal Res. 2018, 29, 113–120.
  191. Sonani, R.; Rastogi, R.; Madamwar, D. Chapter 5-Natural Antioxidants From Algae: A Therapeutic Perspective. In Algal Green Chemistry: Recent Progress in Biotechnology; Rastogi, R.P., Madamwar, D., Pandey, A., Eds.; Elsevier: Amsterdam, The Netherlands, 2017; pp. 91–120.
  192. Heffernan, N.; Brunton, N.P.; FitzGerald, R.J.; Smyth, T.J. Profiling of the molecular weight and structural isomer abundance of macroalgae-derived phlorotannins. Mar. Drugs 2015, 13, 509–528.
  193. Steevensz, A.J.; MacKinnon, S.L.; Hankinson, R.; Craft, C.; Connan, S.; Stengel, D.B.; Melanson, J.E. Profiling phlorotannins in brown macroalgae by liquid chromatography–high resolution mass spectrometry. Phytochem. Anal. 2012, 23, 547–553.
  194. Barwell, C.J.; Blunden, G.; Manandhar, P.D. Isolation and characterization of brown algal polyphenols as inhibitors of α-amylase, lipase and trypsin. J. Appl. Phycol. 1989, 1, 319–323.
  195. Geiselman, J.A.; McConnell, O.J. Polyphenols in brown algae Fucus vesiculosus and Ascophyllum nodosum: Chemical defenses against the marine herbivorous snail, Littorina littorea. J. Chem. Ecol. 1981, 7, 1115–1133.
  196. Connan, S.; Goulard, F.; Stiger, V.; Deslandes, E.; Gall, E.A. Interspecific and temporal variation in phlorotannin levels in an assemblage of brown algae. Bot. Mar. 2004, 47, 410–416.
  197. Kim, S.M.; Kang, S.W.; Jeon, J.-S.; Jung, Y.-J.; Kim, W.-R.; Kim, C.Y.; Um, B.-H. Determination of major phlorotannins in Eisenia bicyclis using hydrophilic interaction chromatography: Seasonal variation and extraction characteristics. Food Chem. 2013, 138, 2399–2406.
  198. Li, Y.; Fu, X.; Duan, D.; Liu, X.; Xu, J.; Gao, X. Extraction and identification of phlorotannins from the brown alga, Sargassum fusiforme (Harvey) Setchell. Mar. Drugs 2017, 15, 49.
  199. Lee, S.-H.; Yong-Li; Karadeniz, F.; Kim, M.-M.; Kim, S.-K. α-Glucosidase and α-amylase inhibitory activities of phloroglucinal derivatives from edible marine brown alga, Ecklonia cava. J. Sci. Food Agric. 2009, 89, 1552–1558.
  200. Abdelhamid, A.; Lajili, S.; Elkaibi, M.; Muller, C.; Majdoub, H.; Jamil, K.; Bouraoui, A. Optimized extraction, preliminary characterization and evaluation of the in vitro anticancer activity of phlorotannin-rich fraction from the brown seaweed, Cystoseira sedoides. J. Aquat. Food Prod. Technol. 2019, 28, 892–909.
  201. Kim, H.-J.; Yong, H.I.; Lee, B.W.; Park, S.; Baek, K.H.; Kim, T.H.; Jo, C. Plasma-polymerized phlorotannins and their enhanced biological activities. J. Agric. Food. Chem. 2020, 68, 2357–2365.
  202. Dong, X.; Bai, Y.; Xu, Z.; Shi, Y.; Sun, Y.; Janaswamy, S.; Yu, C.; Qi, H. Phlorotannins from Undaria pinnatifida sporophyll: Extraction, antioxidant, and anti-inflammatory activities. Mar. Drugs 2019, 17, 434.
  203. Artan, M.; Li, Y.; Karadeniz, F.; Lee, S.-H.; Kim, M.-M.; Kim, S.-K. Anti-HIV-1 activity of phloroglucinol derivative, 6,6′-bieckol, from Ecklonia cava. Biorg. Med. Chem. 2008, 16, 7921–7926.
  204. Zhou, X.; Yi, M.; Ding, L.; He, S.; Yan, X. Isolation and Purification of a neuroprotective phlorotannin from the marine algae Ecklonia maxima by size exclusion and high-speed counter-current chromatography. Mar. Drugs 2019, 17, 212.
  205. Tang, J.; Wang, W.; Chu, W. Antimicrobial and anti-quorum sensing activities of phlorotannins from seaweed (Hizikia fusiforme). Front. Cell. Infect. Microbiol. 2020, 10.
  206. Corona, G.; Ji, Y.; Anegboonlap, P.; Hotchkiss, S.; Gill, C.; Yaqoob, P.; Spencer, J.P.; Rowland, I. Gastrointestinal modifications and bioavailability of brown seaweed phlorotannins and effects on inflammatory markers. Br. J. Nutr. 2016, 115, 1240–1253.
  207. Wang, Y.; Xu, Z.; Bach, S.J.; McAllister, T.A. Effects of phlorotannins from Ascophyllum nodosum (brown seaweed) on in vitro ruminal digestion of mixed forage or barley grain. Anim. Feed Sci. Technol. 2008, 145, 375–395.
  208. Zhao, C.; Yang, C.; Chen, M.; Lv, X.; Liu, B.; Yi, L.; Cornara, L.; Wei, M.-C.; Yang, Y.-C.; Tundis, R.; et al. Regulatory efficacy of brown seaweed Lessonia nigrescens extract on the gene expression profile and intestinal microflora in type 2 diabetic mice. Mol. Nutr. Food Res. 2018, 62, 1700730.
  209. Hirosumi, J.; Tuncman, G.; Chang, L.; Görgün, C.Z.; Uysal, K.T.; Maeda, K.; Karin, M.; Hotamisligil, G.S. A central role for JNK in obesity and insulin resistance. Nature 2002, 420, 333–336.
  210. Yuan, Y.; Zheng, Y.; Zhou, J.; Geng, Y.; Zou, P.; Li, Y.; Zhang, C. Polyphenol-rich extracts from brown macroalgae Lessonia trabeculate attenuate hyperglycemia and modulate gut microbiota in high-fat diet and streptozotocin-induced diabetic rats. J. Agric. Food. Chem. 2019, 67, 12472–12480.
  211. Xu, J.; Liu, T.; Li, Y.; Yuan, C.; Ma, H.; Seeram, N.P.; Liu, F.; Mu, Y.; Huang, X.; Li, L. Hypoglycemic and hypolipidemic effects of triterpenoid-enriched Jamun (Eugenia jambolana Lam.) fruit extract in streptozotocin-induced type 1 diabetic mice. Food Funct. 2018, 9, 3330–3337.
  212. Chang, P.V.; Hao, L.; Offermanns, S.; Medzhitov, R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl Acad. Sci. USA 2014, 111, 2247–2252.
  213. Morgan, X.C.; Tickle, T.L.; Sokol, H.; Gevers, D.; Devaney, K.L.; Ward, D.V.; Reyes, J.A.; Shah, S.A.; LeLeiko, N.; Snapper, S.B.; et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 2012, 13, R79.
  214. Do, M.H.; Lee, H.-B.; Lee, E.; Park, H.-Y. The effects of gelatinized wheat starch and high salt diet on gut microbiota and metabolic disorder. Nutrients 2020, 12, 301.
  215. Wu, T.-R.; Lin, C.-S.; Chang, C.-J.; Lin, T.-L.; Martel, J.; Ko, Y.-F.; Ojcius, D.M.; Lu, C.-C.; Young, J.D.; Lai, H.-C. Gut commensal Parabacteroides goldsteinii plays a predominant role in the anti-obesity effects of polysaccharides isolated from Hirsutella sinensis. Gut 2019, 68, 248–262.
  216. Corona, G.; Coman, M.; Guo, Y.; Hotchkiss, S.; Gill, C.; Yaqoob, P.; Spencer, J.; Rowland, I. Effect of simulated gastrointestinal digestion and fermentation on polyphenolic content and bioactivity of brown seaweed phlorotannin-rich extracts. Mol. Nutr. Food Res. 2017, 61, 1700223.
  217. Fitzgerald, C.; Mora-Soler, L.; Gallagher, E.; O’Connor, P.; Prieto, J.; Soler-Vila, A.; Hayes, M. Isolation and characterization of bioactive pro-peptides with in vitro renin inhibitory activities from the macroalga Palmaria palmata. J. Agric. Food. Chem. 2012, 60, 7421–7427.
  218. Harnedy, P.A.; O’Keeffe, M.B.; FitzGerald, R.J. Purification and identification of dipeptidyl peptidase (DPP) IV inhibitory peptides from the macroalga Palmaria palmata. Food Chem. 2015, 172, 400–406.
  219. Fitzgerald, C.; Gallagher, E.; O’Connor, P.; Prieto, J.; Mora-Soler, L.; Grealy, M.; Hayes, M. Development of a seaweed derived platelet activating factor acetylhydrolase (PAF-AH) inhibitory hydrolysate, synthesis of inhibitory peptides and assessment of their toxicity using the Zebrafish larvae assay. Peptides 2013, 50, 119–124.
  220. Admassu, H.; Gasmalla, M.A.; Yang, R.; Zhao, W. Identification of bioactive peptides with α-amylase inhibitory potential from enzymatic protein hydrolysates of red seaweed (Porphyra spp). J. Agric. Food. Chem. 2018, 66, 4872–4882.
  221. Cian, R.E.; Hernández-Chirlaque, C.; Gámez-Belmonte, R.; Drago, S.R.; Sánchez de Medina, F.; Martínez-Augustin, O. Green alga Ulva spp. hydrolysates and their peptide fractions regulate cytokine production in splenic macrophages and lymphocytes involving the TLR4-NFκB/MAPK pathways. Mar. Drugs 2018, 16, 235.
  222. Minkova, K.M.; Toshkova, R.A.; Gardeva, E.G.; Tchorbadjieva, M.I.; Ivanova, N.J.; Yossifova, L.S.; Gigova, L.G. Antitumor activity of B-phycoerythrin from Porphyridium cruentum. J. Pharm. Res. 2011, 4, 1480–1482. Available online: (accessed on 16 September 2020).
  223. Venkatraman, K.L.; Syed, A.A.; Indumathi, P.; Mehta, A. VITPOR AI, a coagulation factor XIIa inhibitor from Porphyra yezoensis: In vivo mode of action and assessment of platelet function analysis. Protein Pept. Lett. 2020, 27, 243–250.
  224. McLaughlin, C.M.; Sharkey, S.J.; Harnedy-Rothwell, P.; Parthsarathy, V.; Allsopp, P.J.; McSorley, E.M.; FitzGerald, R.J.; O’Harte, F.P.M. Twice daily oral administration of Palmaria palmata protein hydrolysate reduces food intake in streptozotocin induced diabetic mice, improving glycaemic control and lipid profiles. J. Funct. Foods 2020, 73, 104101.
  225. Dave, L.A.; Hayes, M.; Mora, L.; Rutherfurd, S.M.; Montoya, C.A.; Moughan, P.J. Bioactive peptides originating from gastrointestinal endogenous proteins in the growing pig: In vivo identification. Curr. Pharm. Des. 2021, 27, 1382–1395.
  226. Fitzgerald, C.; Aluko, R.E.; Hossain, M.; Rai, D.K.; Hayes, M. Potential of a renin inhibitory peptide from the red seaweed Palmaria palmata as a functional food ingredient following confirmation and characterization of a hypotensive effect in spontaneously hypertensive rats. J. Agric. Food. Chem. 2014, 62, 8352–8356.
  227. Allsopp, P.; Crowe, W.; Bahar, B.; Harnedy, P.A.; Brown, E.S.; Taylor, S.S.; Smyth, T.J.; Soler-Vila, A.; Magee, P.J.; Gill, C.I.R.; et al. The effect of consuming Palmaria palmata-enriched bread on inflammatory markers, antioxidant status, lipid profile and thyroid function in a randomised placebo-controlled intervention trial in healthy adults. Eur. J. Nutr. 2016, 55, 1951–1962.
  228. Furuta, T.; Miyabe, Y.; Yasui, H.; Kinoshita, Y.; Kishimura, H. Angiotensin I converting enzyme inhibitory peptides derived from phycobiliproteins of dulse Palmaria palmata. Mar. Drugs 2016, 14, 32.
  229. Sato, M.; Hosokawa, T.; Yamaguchi, T.; Nakano, T.; Muramoto, K.; Kahara, T.; Funayama, K.; Kobayashi, A.; Nakano, T. Angiotensin I-converting enzyme inhibitory peptides derived from Wakame (Undaria pinnatifida) and their antihypertensive effect in spontaneously hypertensive rats. J. Agric. Food. Chem. 2002, 50, 6245–6252.
  230. Suetsuna, K.; Nakano, T. Identification of an antihypertensive peptide from peptic digest of wakame (Undaria pinnatifida). J. Nutr. Biochem. 2000, 11, 450–454.
  231. Harnedy, P.A.; O’Keeffe, M.B.; FitzGerald, R.J. Fractionation and identification of antioxidant peptides from an enzymatically hydrolysed Palmaria palmata protein isolate. Food Res. Int. 2017, 100, 416–422.
  232. Amaretti, A.; Gozzoli, C.; Simone, M.; Raimondi, S.; Righini, L.; Pérez-Brocal, V.; García-López, R.; Moya, A.; Rossi, M. Profiling of protein degraders in cultures of human gut microbiota. Front. Microbiol. 2019, 10.
  233. Neis, E.P.J.G.; Dejong, C.H.C.; Rensen, S.S. The role of microbial amino acid metabolism in host metabolism. Nutrients 2015, 7, 2930–2946.
  234. Diether, N.E.; Willing, B.P. Microbial fermentation of dietary protein: An important factor in diet-microbe-host interaction. Microorganisms 2019, 7, 19.
  235. Fan, P.; Li, L.; Rezaei, A.; Eslamfam, S.; Che, D.; Ma, X. Metabolites of dietary protein and peptides by intestinal microbes and their impacts on gut. Curr. Protein Pept. Sci. 2015, 16, 646–654.
  236. Oliphant, K.; Allen-Vercoe, E. Macronutrient metabolism by the human gut microbiome: Major fermentation by-products and their impact on host health. Microbiome 2019, 7, 91.
  237. Kim, J.; Hetzel, M.; Boiangiu, C.D.; Buckel, W. Dehydration of (R)-2-hydroxyacyl-CoA to enoyl-CoA in the fermentation of α-amino acids by anaerobic bacteria. FEMS Microbiol. Rev. 2004, 28, 455–468.
  238. Blachier, F.; Mariotti, F.; Huneau, J.F.; Tomé, D. Effects of amino acid-derived luminal metabolites on the colonic epithelium and physiopathological consequences. Amino Acids 2007, 33, 547–562.
  239. Feng, W.; Ao, H.; Peng, C. Gut microbiota, short-chain fatty acids, and herbal medicines. Front. Pharmacol. 2018, 9, 1354.
  240. Portune, K.J.; Beaumont, M.; Davila, A.-M.; Tomé, D.; Blachier, F.; Sanz, Y. Gut microbiota role in dietary protein metabolism and health-related outcomes: The two sides of the coin. Trends Food Sci. Technol. 2016, 57 Pt B, 213–232.
  241. Yao, C.K.; Muir, J.G.; Gibson, P.R. Review article: Insights into colonic protein fermentation, its modulation and potential health implications. Aliment. Pharmacol. Ther. 2016, 43, 181–196.
  242. Korpela, K. Diet, microbiota, and metabolic health: Trade-off between saccharolytic and proteolytic fermentation. Annu. Rev. Food Sci. Technol. 2018, 9, 65–84.
  243. Wang, X.; Gibson, G.R.; Costabile, A.; Sailer, M.; Theis, S.; Rastall, R.A. Prebiotic supplementation of in vitro fecal fermentations inhibits proteolysis by gut bacteria, and host diet shapes gut bacterial metabolism and response to intervention. Appl. Environ. Microbiol. 2019, 85, e02749-18.
  244. Lee, M.K.; Kim, I.H.; Choi, Y.H.; Nam, T.J. A peptide from Porphyra yezoensis stimulates the proliferation of IEC-6 cells by activating the insulin-like growth factor I receptor signaling pathway. Int. J. Mol. Med. 2015, 35, 533–538.
  245. Remacle-Bonnet, M.; Garrouste, F.; Baillat, G.; Andre, F.; Marvaldi, J.; Pommier, G. Membrane rafts segregate pro- from anti-apoptotic insulin-like growth factor-I receptor signaling in colon carcinoma cells stimulated by members of the tumor necrosis factor superfamily. Am. J. Pathol. 2005, 167, 761–773.
  246. Braicu, C.; Buse, M.; Busuioc, C.; Drula, R.; Gulei, D.; Raduly, L.; Rusu, A.; Irimie, A.; Atanasov, A.G.; Slaby, O.; et al. A comprehensive review on MAPK: A promising therapeutic target in cancer. Cancers 2019, 11, 1618.
  247. Lee, M.-K.; Kim, I.-H.; Choi, Y.-H.; Choi, J.-W.; Kim, Y.-M.; Nam, T.-J. The proliferative effects of Pyropia yezoensis peptide on IEC-6 cells are mediated through the epidermal growth factor receptor signaling pathway. Int. J. Mol. Med. 2015, 35, 909–914.
  248. Katz, M.; Amit, I.; Yarden, Y. Regulation of MAPKs by growth factors and receptor tyrosine kinases. Biochim. Biophys. Acta Bioenerg. 2007, 1773, 1161–1176.
  249. Li, L.; Zhao, G.D.; Shi, Z.; Qi, L.L.; Zhou, L.Y.; Fu, Z.X. The Ras/Raf/MEK/ERK signaling pathway and its role in the occurrence and development of HCC. Oncol. Lett. 2016, 12, 3045–3050.
  250. Klopfleisch, R.; Gruber, A.D. Differential expression of cell cycle regulators p21, p27 and p53 in metastasizing canine mammary adenocarcinomas versus normal mammary glands. Res. Vet. Sci. 2009, 87, 91–96.
  251. Paunovic, B.; Khomenko, T.; Deng, X.; Xiong, X.; Sandor, Z.; Szabo, S. Overexpression of cyclin-dependent kinase (CDK) inhibitors p21 and p27 is a common mechanism of experimental duodenal ulcer and ulcerative colitis. FASEB J. 2010, 24, 1027.4.
  252. Abdelhedi, O.; Nasri, M. Basic and recent advances in marine antihypertensive peptides: Production, structure-activity relationship and bioavailability. Trends Food Sci. Technol. 2019, 88, 543–557.
  253. Samarakoon, K.; Jeon, Y.-J. Bio-functionalities of proteins derived from marine algae: A review. Food Res. Int. 2012, 48, 948–960.
  254. Vizcaíno, A.J.; Galafat, A.; Sáez, M.I.; Martínez, T.F.; Alarcón, F.J. Partial characterization of protease inhibitors of Ulva ohnoi and their effect on digestive proteases of marine fish. Mar. Drugs 2020, 18, 319.
  255. Mahomoodally, M.F.; Bibi Sadeer, N.; Zengin, G.; Cziáky, Z.; Jekő, J.; Diuzheva, A.; Sinan, K.I.; Palaniveloo, K.; Kim, D.H.; Rengasamy, K.R.R. In vitro enzyme inhibitory properties, secondary metabolite profiles and multivariate analysis of five seaweeds. Mar. Drugs 2020, 18, 198.
  256. Pan, S.; Wang, S.; Jing, L.; Yao, D. Purification and characterisation of a novel angiotensin-I converting enzyme (ACE)-inhibitory peptide derived from the enzymatic hydrolysate of Enteromorpha clathrata protein. Food Chem. 2016, 211, 423–430.
  257. Rein, M.J.; Renouf, M.; Cruz-Hernandez, C.; Actis-Goretta, L.; Thakkar, S.K.; da Silva Pinto, M. Bioavailability of bioactive food compounds: A challenging journey to bioefficacy. Br. J. Clin. Pharmacol. 2013, 75, 588–602.
  258. Nova, P.; Pimenta-Martins, A.; Laranjeira Silva, J.; Silva, A.M.; Gomes, A.M.; Freitas, A.C. Health benefits and bioavailability of marine resources components that contribute to health–what’s new? Crit. Rev. Food Sci. Nutr. 2020, 1–13.
  259. Thakur, N.; Raigond, P.; Singh, Y.; Mishra, T.; Singh, B.; Lal, M.K.; Dutt, S. Recent updates on bioaccessibility of phytonutrients. Trends Food Sci. Technol. 2020, 97, 366–380.
  260. Alegría, A.; Garcia-Llatas, G.; Cilla, A. Chapter 1-Static digestion models: General introduction. In The Impact of Food Bioactives on Health: In Vitro and Ex Vivo Models; Verhoeckx, K., Cotter, P., López-Expósito, I., Kleiveland, C., Lea, T., Mackie, A., Requena, T., Swiatecka, D., Wichers, H., Eds.; Springer: Cham, Switzerland, 2015; pp. 3–12.
  261. Plank, D.W. In Vitro Method for Estimating In Vivo Protein Digestibility; General Mills Inc.: Minneapolis, MN, USA, 2017; Available online: (accessed on 19 July 2020).
  262. Bohn, T.; Carrière, F.; Day, L.; Deglaire, A.; Egger, L.; Freitas, D.; Golding, M.; Lefeunteun, S.; Macierzanka, A.; Ménard, O.; et al. Correlation between in vitro and in vivo data on food digestion. What can we predict with static in vitro digestion models? Crit. Rev. Food Sci. Nutr. 2017, 58, 2239–2261.
  263. Dima, C.; Assadpour, E.; Dima, S.; Jafari, S.M. Bioavailability and bioaccessibility of food bioactive compounds; overview and assessment by in vitro methods. Compr. Rev. Food Sci. Food Saf. 2020, 19, 2862–2884.
  264. Alminger, M.; Aura, A.-M.; Bohn, T.; Dufour, C.; El, S.N.; Gomes, A.; Karakaya, S.; Martínez-Cuesta, M.C.; McDougall, G.J.; Requena, T.; et al. In vitro models for studying secondary plant metabolite digestion and bioaccessibility. Compr. Rev. Food Sci. Food Saf. 2014, 13, 413–436.
  265. Egger, L.; Ménard, O.; Delgado-Andrade, C.; Alvito, P.; Assunção, R.; Balance, S.; Barberá, R.; Brodkorb, A.; Cattenoz, T.; Clemente, A.; et al. The harmonized INFOGEST in vitro digestion method: From knowledge to action. Food Res. Int. 2016, 88, 217–225.
  266. Etcheverry, P.; Grusak, M.A.; Fleige, L.E. Application of in vitro bioaccessibility and bioavailability methods for calcium, carotenoids, folate, iron, magnesium, polyphenols, zinc, and vitamins B6, B12, D, and E. Front. Physiol. 2012, 3, 317.
  267. Laparra, J.M.; Vélez, D.; Montoro, R.; Barberá, R.; Farré, R. Estimation of arsenic bioaccessibility in edible seaweed by an in vitro digestion method. J. Agric. Food. Chem. 2003, 51, 6080–6085.
  268. Miller, D.D.; Schricker, B.R.; Rasmussen, R.R.; Van Campen, D. An in vitro method for estimation of iron availability from meals. Am. J. Clin. Nutr. 1981, 34, 2248–2256.
  269. Minekus, M.; Alminger, M.; Alvito, P.; Ballance, S.; Bohn, T.; Bourlieu, C.; Carriere, F.; Boutrou, R.; Corredig, M.; Dupont, D. A standardised static in vitro digestion method suitable for food–an international consensus. Food Funct. 2014, 5, 1113–1124.
  270. Boisen, S.; Eggum, B. Critical evaluation of in vitro methods for estimating digestibility in simple-stomach animals. Nutr. Res. Rev. 1991, 4, 141–162.
  271. Dupont, D.; Bordoni, A.; Brodkorb, A.; Capozzi, F.; Velickovic, T.C.; Corredig, M.; Cotter, P.D.; De Noni, I.; Gaudichon, C.; Golding, M. An international network for improving health properties of food by sharing our knowledge on the digestive process. Food Dig. 2011, 2, 23–25.
  272. Afonso, C.; Cardoso, C.; Ripol, A.; Varela, J.; Quental-Ferreira, H.; Pousão-Ferreira, P.; Ventura, M.S.; Delgado, I.M.; Coelho, I.; Castanheira, I.; et al. Composition and bioaccessibility of elements in green seaweeds from fish pond aquaculture. Food Res. Int. 2018, 105, 271–277.
  273. Soukoulis, C.; Tsevdou, M.; Andre, C.M.; Cambier, S.; Yonekura, L.; Taoukis, P.S.; Hoffmann, L. Modulation of chemical stability and in vitro bioaccessibility of beta-carotene loaded in kappa-carrageenan oil-in-gel emulsions. Food Chem. 2017, 220, 208–218.
  274. Kazir, M.; Abuhassira, Y.; Robin, A.; Nahor, O.; Luo, J.; Israel, A.; Golberg, A.; Livney, Y.D. Extraction of proteins from two marine macroalgae, Ulva sp. and Gracilaria sp. for food application, and evaluating digestibility, amino acid composition and antioxidant properties of the protein concentrates. Food Hydrocoll. 2019, 87, 194–203.
  275. Guerra, A.; Etienne-Mesmin, L.; Livrelli, V.; Denis, S.; Blanquet-Diot, S.; Alric, M. Relevance and challenges in modeling human gastric and small intestinal digestion. Trends Biotechnol. 2012, 30, 591–600.
  276. Thuenemann, E.C.; Mandalari, G.; Rich, G.T.; Faulks, R.M. Chapter 6-Dynamic gastric model (DGM). In The Impact of Food Bioactives on Health: In Vitro and Ex Vivo Models; Verhoeckx, K., Cotter, P., López-Expósito, I., Kleiveland, C., Lea, T., Mackie, A., Requena, T., Swiatecka, D., Wichers, H., Eds.; Springer: Cham, Switzerland, 2015; pp. 47–59.
  277. Minekus, M.; Marteau, P.; Havenaar, R.; Veld, J.H.H.I.T. A multicompartmental dynamic computer-controlled model simulating the stomach and small intestine. Altern. Lab. Anim. 1995, 23, 197–209.
  278. Etienne-Mesmin, L.; Livrelli, V.; Privat, M.; Denis, S.; Cardot, J.-M.; Alric, M.; Blanquet-Diot, S. Effect of a new probiotic Saccharomyces cerevisiae strain on survival of Escherichia coli 0157:H7 in a dynamic gastrointestinal model. Appl. Environ. Microbiol. 2011, 77, 1127–1131.
  279. Larsson, M.; Minekus, M.; Havenaar, R. Estimation of the bioavailability of iron and phosphorus in cereals using a dynamic in vitro gastrointestinal model. J. Sci. Food Agric. 1997, 74, 99–106.
  280. Verwei, M.; Freidig, A.P.; Havenaar, R.; Groten, J.P. Predicted serum folate concentrations based on in vitro studies and kinetic modeling are consistent with measured folate concentrations in humans. J. Nutr. 2006, 136, 3074–3078.
  281. Mateo Anson, N.; Havenaar, R.; Bast, A.; Haenen, G.R.M.M. Antioxidant and anti-inflammatory capacity of bioaccessible compounds from wheat fractions after gastrointestinal digestion. J. Cereal Sci. 2010, 51, 110–114.
  282. Torres-Escribano, S.; Denis, S.; Blanquet-Diot, S.; Calatayud, M.; Barrios, L.; Vélez, D.; Alric, M.; Montoro, R. Comparison of a static and a dynamic in vitro model to estimate the bioaccessibility of As, Cd, Pb and Hg from food reference materials Fucus sp. (IAEA-140/TM) and Lobster hepatopancreas (TORT-2). Sci. Total Environ. 2011, 409, 604–611.
  283. Bellmann, S.; Miyazaki, K.; Chonan, O.; Ishikawa, F.; Havenaar, R. Fucoidan from Cladosiphon okamuranus Tokida added to food has no adverse effect on availability for absorption of divalent minerals in the dynamic multicompartmental model of the upper gastrointestinal tract. Food Digestion 2014, 5, 19–25.
  284. Blanquet, S.; Zeijdner, E.; Beyssac, E.; Meunier, J.-P.; Denis, S.; Havenaar, R.; Alric, M. A dynamic artificial gastrointestinal system for studying the behavior of orally administered drug dosage forms under various physiological conditions. Pharm. Res. 2004, 21, 585–591.
  285. Wickham, M.; Faulks, R.; Mann, J.; Mandalari, G. The design, operation, and application of a dynamic gastric model. Dissolut. Technol. 2012, 19, 15–22.
  286. Vardakou, M.; Mercuri, A.; Barker, S.; Craig, D.; Faulks, R.; Wickham, M. Achieving antral grinding forces in biorelevant in vitro models: Comparing the USP Dissolution Apparatus II and the Dynamic Gastric Model with human in vivo data. AAPS PharmSciTech. 2011, 12, 620–626.
  287. Marciani, L.; Gowland, P.A.; Fillery-Travis, A.; Manoj, P.; Wright, J.; Smith, A.; Young, P.; Moore, R.; Spiller, R.C. Assessment of antral grinding of a model solid meal with echo-planar imaging. Am. J. Physiol. Gastrointest. Liver Physiol. 2001, 280, G844–G849.
  288. Lea, T. Chapter 9-Epithelial cell models; general introduction. In The Impact of Food Bioactives on Health: In Vitro and Ex Vivo Models; Verhoeckx, K., Cotter, P., López-Expósito, I., Kleiveland, C., Lea, T., Mackie, A., Requena, T., Swiatecka, D., Wichers, H., Eds.; Springer: Cham, Switzerland, 2015; pp. 95–102.
  289. Lv, Q.; He, Q.; Wu, Y.; Chen, X.; Ning, Y.; Chen, Y. Investigating the bioaccessibility and bioavailability of cadmium in a cooked rice food matrix by using an 11-day rapid Caco-2/HT-29 co-culture cell model combined with an in vitro digestion model. Biol. Trace Elem. Res. 2019, 190, 336–348.
  290. Kuhre, R.E.; Wewer Albrechtsen, N.J.; Deacon, C.F.; Balk-Møller, E.; Rehfeld, J.F.; Reimann, F.; Gribble, F.M.; Holst, J.J. Peptide production and secretion in GLUTag, NCI-H716, and STC-1 cells: A comparison to native L-cells. J. Mol. Endocrinol. 2016, 56, 201–211.
  291. Reggi, S.; Giromini, C.; Dell’Anno, M.; Baldi, A.; Rebucci, R.; Rossi, L. In vitro digestion of chestnut and quebracho tannin extracts: Antimicrobial effect, antioxidant capacity and cytomodulatory activity in swine intestinal IPEC-J2 cells. Animals 2020, 10, 195.
  292. Sambuy, Y.; De Angelis, I.; Ranaldi, G.; Scarino, M.L.; Stammati, A.; Zucco, F. The Caco-2 cell line as a model of the intestinal barrier: Influence of cell and culture-related factors on Caco-2 cell functional characteristics. Cell Biol. Toxicol. 2005, 21, 1–26.
  293. Glahn, R.P.; Wien, E.M.; van Campen, D.R.; Miller, D.D. Caco-2 cell iron uptake from meat and casein digests parallels in vivo studies: Use of a novel in vitro method for rapid estimation of iron bioavailability. J. Nutr. 1996, 126, 332–339.
  294. Trigo, J.P.; Engström, N.; Steinhagen, S.; Juul, L.; Harrysson, H.; Toth, G.B.; Pavia, H.; Scheers, N.; Undeland, I. In vitro digestibility and Caco-2 cell bioavailability of sea lettuce (Ulva fenestrata) proteins extracted using pH-shift processing. Food Chem. 2021, 356, 129683.
  295. Flores, S.R.L.; Dobbs, J.; Dunn, M.A. Mineral nutrient content and iron bioavailability in common and Hawaiian seaweeds assessed by an in vitro digestion/Caco-2 cell model. J. Food Compos. Anal. 2015, 43, 185–193.
  296. Domínguez-González, M.R.; Chiocchetti, G.M.; Herbello-Hermelo, P.; Vélez, D.; Devesa, V.; Bermejo-Barrera, P. Evaluation of iodine bioavailability in seaweed using in vitro methods. J. Agric. Food. Chem. 2017, 65, 8435–8442.
  297. Hur, S.J.; Lim, B.O.; Decker, E.A.; McClements, D.J. In vitro human digestion models for food applications. Food Chem. 2011, 125, 1–12.
  298. Boisen, S.; Fernández, J.A. Prediction of the total tract digestibility of energy in feedstuffs and pig diets by in vitro analyses. Anim. Feed Sci. Technol. 1997, 68, 277–286.
  299. Hayes, M. Food proteins and bioactive peptides: New and novel sources, characterisation strategies and applications. Foods 2018, 7, 38.
  300. Popova, A.; Mihaylova, D. Antinutrients in plant-based foods: A review. Open Biotechnol. J. 2019, 13, 68–76.
  301. Fabiano, A.; Brilli, E.; Mattii, L.; Testai, L.; Moscato, S.; Citi, V.; Tarantino, G.; Zambito, Y. Ex vivo and in vivo study of Sucrosomial® iron intestinal absorption and bioavailability. Int. J. Mol. Sci. 2018, 19, 2722.
  302. Ussing, H.H. The active ion transport through the isolated frog skin in the light of tracer studies. Acta Physiol. Scand. 1949, 17, 1–37.
  303. Clarke, L.L. A guide to Ussing chamber studies of mouse intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 2009, 296, G1151–G1166.
  304. Awati, A.; Rutherfurd, S.M.; Plugge, W.; Reynolds, G.W.; Marrant, H.; Kies, A.K.; Moughan, P.J. Ussing chamber results for amino acid absorption of protein hydrolysates in porcine jejunum must be corrected for endogenous protein. J. Sci. Food Agric. 2009, 89, 1857–1861.
  305. Westerhout, J.; Wortelboer, H.; Verhoeckx, K. Chapter 24-Ussing chamber. In The Impact of Food Bioactives on Health: In Vitro and Ex Vivo Models; Verhoeckx, K., Cotter, P., López-Expósito, I., Kleiveland, C., Lea, T., Mackie, A., Requena, T., Swiatecka, D., Wichers, H., Eds.; Springer: Cham, Switzerland, 2015; pp. 263–273.
  306. Luo, Z.; Liu, Y.; Zhao, B.; Tang, M.; Dong, H.; Zhang, L.; Lv, B.; Wei, L. Ex vivo and in situ approaches used to study intestinal absorption. J. Pharmacol. Toxicol. Methods 2013, 68, 208–216.
  307. Agar, W.T.; Hird, F.J.R.; Sidhu, G.S. The uptake of amino acids by the intestine. Biochim. Biophys. Acta 1954, 14, 80–84.
  308. Hillgren, K.M.; Kato, A.; Borchardt, R.T. In vitro systems for studying intestinal drug absorption. Med. Res. Rev. 1995, 15, 83–109.
  309. Nossol, C.; Barta-Böszörményi, A.; Kahlert, S.; Zuschratter, W.; Faber-Zuschratter, H.; Reinhardt, N.; Ponsuksili, S.; Wimmers, K.; Diesing, A.-K.; Rothkötter, H.-J. Comparing two intestinal porcine epithelial cell lines (IPECs): Morphological differentiation, function and metabolism. PLoS ONE 2015, 10, e0132323.
  310. Ripken, D.; Hendriks, H. Chapter 23-Porcine ex vivo intestinal segment model. In The Impact of Food Bioactives on Health: In Vitro and Ex Vivo Models; Verhoeckx, K., Cotter, P., López-Expósito, I., Kleiveland, C., Lea, T., Mackie, A., Requena, T., Swiatecka, D., Wichers, H., Eds.; Springer: Cham, Switzerland, 2015; pp. 255–262.
  311. Pearce, S.C.; Coia, H.G.; Karl, J.P.; Pantoja-Feliciano, I.G.; Zachos, N.C.; Racicot, K. Intestinal in vitro and ex vivo models to study host-microbiome interactions and acute stressors. Front. Physiol. 2018, 9.
  312. Roeselers, G.; Ponomarenko, M.; Lukovac, S.; Wortelboer, H.M. Ex vivo systems to study host–microbiota interactions in the gastrointestinal tract. Best Pract. Res. Clin. Gastroenterol. 2013, 27, 101–113.
  313. van de Merbel, A.F.; van der Horst, G.; van der Mark, M.H.; van Uhm, J.I.M.; van Gennep, E.J.; Kloen, P.; Beimers, L.; Pelger, R.C.M.; van der Pluijm, G. An ex vivo tissue culture model for the assessment of individualized drug responses in prostate and bladder cancer. Front. Oncol. 2018, 8.
  314. Ripken, D.; van der Wielen, N.; Wortelboer, H.M.; Meijerink, J.; Witkamp, R.F.; Hendriks, H.F.J. Steviol glycoside rebaudioside a induces glucagon-like peptide-1 and peptide yy release in a porcine ex vivo intestinal model. J. Agric. Food. Chem. 2014, 62, 8365–8370.
  315. Aura, A.-M.; Maukonen, J. Chapter 25-One compartment fermentation model. In The Impact of Food Bioactives on Health: In Vitro and Ex Vivo Models; Verhoeckx, K., Cotter, P., López-Expósito, I., Kleiveland, C., Lea, T., Mackie, A., Requena, T., Swiatecka, D., Wichers, H., Eds.; Springer: Cham, Switzerland, 2015; pp. 281–292.
  316. Ouwehand, A.C.; Tiihonen, K.; Mäkeläinen, H.; Rautonen, N.; Hasselwander, O.; Sworn, G. Chapter 5-Non-starch polysaccharides in the gastrointestinal tract. In Designing Functional Foods; McClements, D.J., Decker, E.A., Eds.; Woodhead Publishing: Cambridge, UK, 2009; pp. 126–147.
  317. Gibson, G.R.; Cummings, J.H.; Macfarlane, G.T. Use of a three-stage continuous culture system to study the effect of mucin on dissimilatory sulfate reduction and methanogenesis by mixed populations of human gut bacteria. Appl. Environ. Microbiol. 1988, 54, 2750–2755.
  318. Molly, K.; Vande Woestyne, M.; Verstraete, W. Development of a 5-step multi-chamber reactor as a simulation of the human intestinal microbial ecosystem. Appl. Microbiol. Biotechnol. 1993, 39, 254–258.
  319. Van den Abbeele, P.; Grootaert, C.; Marzorati, M.; Possemiers, S.; Verstraete, W.; Gérard, P.; Rabot, S.; Bruneau, A.; El Aidy, S.; Derrien, M. Microbial community development in a dynamic gut model is reproducible, colon region specific, and selective for Bacteroidetes and Clostridium cluster IX. Appl. Environ. Microbiol. 2010, 76, 5237–5246.
  320. Possemiers, S.; Rabot, S.; Espín, J.C.; Bruneau, A.; Philippe, C.; González-Sarrías, A.; Heyerick, A.; Tomás-Barberán, F.A.; De Keukeleire, D.; Verstraete, W. Eubacterium limosum activates isoxanthohumol from hops (Humulus lupulus L.) into the potent phytoestrogen 8-prenylnaringenin in vitro and in rat intestine. J. Nutr. 2008, 138, 1310–1316.
  321. Van den Abbeele, P.; Roos, S.; Eeckhaut, V.; MacKenzie, D.A.; Derde, M.; Verstraete, W.; Marzorati, M.; Possemiers, S.; Vanhoecke, B.; Van Immerseel, F. Incorporating a mucosal environment in a dynamic gut model results in a more representative colonization by Lactobacilli. Microb. Biotechnol. 2012, 5, 106–115.
  322. Marzorati, M.; Verhelst, A.; Luta, G.; Sinnott, R.; Verstraete, W.; de Wiele, T.V.; Possemiers, S. In vitro modulation of the human gastrointestinal microbial community by plant-derived polysaccharide-rich dietary supplements. Int. J. Food Microbiol. 2010, 139, 168–176.
  323. Fu, Y.; Yin, N.; Cai, X.; Du, H.; Wang, P.; Sultana, M.S.; Sun, G.; Cui, Y. Arsenic speciation and bioaccessibility in raw and cooked seafood: Influence of seafood species and gut microbiota. Environ. Pollut. 2021, 280, 116958.
  324. Calatayud, M.; Xiong, C.; Du Laing, G.; Raber, G.; Francesconi, K.; van de Wiele, T. Salivary and gut microbiomes play a significant role in in vitro oral bioaccessibility, biotransformation, and intestinal absorption of arsenic from food. Environ. Sci. Technol. 2018, 52, 14422–14435.
  325. Boever, P.D.; Wouters, R.; Vermeirssen, V.; Boon, N.; Verstraete, W. Development of a six-stage culture system for simulating the gastrointestinal microbiota of weaned infants. Microb. Ecol. Health Dis. 2001, 13, 111–123.
  326. Van de Wiele, T.; Van den Abbeele, P.; Ossieur, W.; Possemiers, S.; Marzorati, M. Chapter 27-The simulator of the human intestinal microbial ecosystem (SHIME®). In The Impact of Food Bioactives on Health: In Vitro and Ex Vivo Models; Verhoeckx, K., Cotter, P., López-Expósito, I., Kleiveland, C., Lea, T., Mackie, A., Requena, T., Swiatecka, D., Wichers, H., Eds.; Springer: Cham, Switzerland, 2015; pp. 305–317.
  327. Williams, C.; Walton, G.; Jiang, L.; Plummer, S.; Garaiova, I.; Gibson, G. Comparative analysis of intestinal tract models. Annu. Rev. Food Sci. Technol. 2015, 6.
  328. Barroso, E.; Cueva, C.; Peláez, C.; Martínez-Cuesta, M.C.; Requena, T. Development of human colonic microbiota in the computer-controlled dynamic SIMulator of the GastroIntestinal tract SIMGI. LWT 2015, 61, 283–289.
  329. Barroso, E.; Cueva, C.; Peláez, C.; Martínez-Cuesta, M.C.; Requena, T. Chapter 28-The computer-controlled multicompartmental dynamic model of the gastrointestinal system SIMGI. In The Impact of Food Bioactives on Health: In Vitro and Ex Vivo Models; Verhoeckx, K., Cotter, P., López-Expósito, I., Kleiveland, C., Lea, T., Mackie, A., Requena, T., Swiatecka, D., Wichers, H., Eds.; Springer: Cham, Switzerland, 2015; pp. 319–327.
  330. Payne, A.; Zihler, A.; Chassard, C.; Lacroix, C. Advances and perspectives in in vitro human gut fermentation modeling. Trends Biotechnol. 2011, 30, 17–25.
  331. Nissen, L.; Casciano, F.; Gianotti, A. Intestinal fermentation in vitro models to study food-induced gut microbiota shift: An updated review. FEMS Microbiol. Lett. 2020, 367.
  332. Wissenbach, D.K.; Oliphant, K.; Rolle-Kampczyk, U.; Yen, S.; Höke, H.; Baumann, S.; Haange, S.B.; Verdu, E.F.; Allen-Vercoe, E.; von Bergen, M. Optimization of metabolomics of defined in vitro gut microbial ecosystems. Int. J. Med. Microbiol. 2016, 306, 280–289.
  333. Marzorati, M.; Vanhoecke, B.; De Ryck, T.; Sadaghian Sadabad, M.; Pinheiro, I.; Possemiers, S.; Van den Abbeele, P.; Derycke, L.; Bracke, M.; Pieters, J.; et al. The HMI™ module: A new tool to study the Host-Microbiota Interaction in the human gastrointestinal tract in vitro. BMC Microbiol. 2014, 14, 133.
  334. Venema, K.; van den Abbeele, P. Experimental models of the gut microbiome. Best Pract. Res. Clin. Gastroenterol. 2013, 27, 115–126.
  335. Wood, R.J.; Tamura, T. Methodological issues in assessing bioavailability of nutrients and other bioactive substances in dietary supplements: Summary of workshop discussion. J. Nutr. 2001, 131, 1396S–1398S.
  336. Carbonell-Capella, J.M.; Buniowska, M.; Barba, F.J.; Esteve, M.J.; Frígola, A. Analytical methods for determining bioavailability and bioaccessibility of bioactive compounds from fruits and vegetables: A review. Compr. Rev. Food Sci. Food 2014, 13, 155–171.
  337. Jahreis, G.; Hausmann, W.; Kiessling, G.; Franke, K.; Leiterer, M. Bioavailability of iodine from normal diets rich in dairy products-results of balance studies in women. Exp. Clin. Endocrinol. Diabetes 2001, 109, 163–167.
  338. Lu, Y.L.; Li, S.J.; Liu, G.Y.; Li, X.C.; Yang, D.; Jia, J.Y.; Zhang, M.Q.; Zheng, H.C.; Yu, C.; Zhu, F.; et al. Oral bioavailability and mass balance studies of a novel anti-arrhythmic agent sulcardine sulfate in Sprague-Dawley rats and beagle dogs. Eur. J. Drug Metab. Pharmacokinet. 2017, 42, 453–459.
  339. Shin, B.S.; Hong, S.H.; Bulitta, J.B.; Hwang, S.W.; Kim, H.J.; Lee, J.B.; Yang, S.D.; Kim, J.E.; Yoon, H.S.; Kim, D.J.; et al. Disposition, oral bioavailability, and tissue distribution of zearalenone in rats at various dose levels. J. Toxicol. Environ. Health A 2009, 72, 1406–1411.
  340. Bohn, T.; Desmarchelier, C.; Dragsted, L.O.; Nielsen, C.S.; Stahl, W.; Rühl, R.; Keijer, J.; Borel, P. Host-related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans. Mol. Nutr. Food Res. 2017, 61, 1600685.
  341. Manach, C.; Scalbert, A.; Morand, C.; Rémésy, C.; Jiménez, L. Polyphenols: Food sources and bioavailability. Am. J. Clin. Nutr. 2004, 79, 727–747.
  342. Dias, D.M.; Costa, N.M.B.; Nutti, M.R.; Tako, E.; Martino, H.S.D. Advantages and limitations of in vitro and in vivo methods of iron and zinc bioavailability evaluation in the assessment of biofortification program effectiveness. Crit. Rev. Food Sci. Nutr. 2018, 58, 2136–2146.
  343. García, Y.; Díaz-Castro, J. Advantages and disadvantages of the animal models v. in vitro studies in iron metabolism: A review. Animal 2013, 7, 1651–1658.
  344. Martinez, M.N.; Rathbone, M.J.; Burgess, D.; Huynh, M. Breakout session summary from AAPS/CRS joint workshop on critical variables in the in vitro and in vivo performance of parenteral sustained release products. J. Control. Release 2010, 142, 2–7.
  345. Gibson, T.M.; Ferrucci, L.M.; Tangrea, J.A.; Schatzkin, A. Epidemiological and clinical studies of nutrition. Semin. Oncol. 2010, 37, 282–296.
  346. Huang, J.; Liu, C.; Wang, Y.; Wang, C.; Xie, M.; Qian, Y.; Fu, L. Application of in vitro and in vivo models in the study of food allergy. Food Sci. Hum. Wellness 2018, 7, 235–243.
  347. Gueven, N.; Spring, K.J.; Holmes, S.; Ahuja, K.; Eri, R.; Park, A.Y.; Fitton, J.H. Micro RNA expression after ingestion of fucoidan; a clinical study. Mar. Drugs 2020, 18, 143.
  348. Ikeda-Ohtsubo, W.; López Nadal, A.; Zaccaria, E.; Iha, M.; Kitazawa, H.; Kleerebezem, M.; Brugman, S. Intestinal microbiota and immune modulation in Zebrafish by fucoidan from Okinawa mozuku (Cladosiphon okamuranus). Front. Nutr. 2020, 7.
  349. Roche-Lima, A.; Carrasquillo-Carrión, K.; Gómez-Moreno, R.; Cruz, J.M.; Velázquez-Morales, D.M.; Rogozin, I.B.; Baerga-Ortiz, A. The presence of genotoxic and/or pro-inflammatory bacterial genes in gut metagenomic databases and their possible link with inflammatory bowel diseases. Front. Genet. 2018, 9.
  350. Nagamine, T.; Nakazato, K.; Tomioka, S.; Iha, M.; Nakajima, K. Intestinal absorption of fucoidan extracted from the brown seaweed, Cladosiphon okamuranus. Mar. Drugs 2015, 13, 48–64.
  351. Kadena, K.; Tomori, M.; Iha, M.; Nagamine, T. Absorption study of mozuku fucoidan in Japanese volunteers. Mar. Drugs 2018, 16, 254.
  352. Tokita, Y.; Nakajima, K.; Mochida, H.; Iha, M.; Nagamine, T. Development of a fucoidan-specific antibody and measurement of fucoidan in serum and urine by sandwich ELISA. Biosci. Biotechnol. Biochem. 2010, 74, 350.
  353. Mathieu, S.; Touvrey-Loiodice, M.; Poulet, L.; Drouillard, S.; Vincentelli, R.; Henrissat, B.; Skjåk-Bræk, G.; Helbert, W. Ancient acquisition of “alginate utilization loci” by human gut microbiota. Sci. Rep. 2018, 8, 8075.
  354. Song, T.; Xu, H.; Wei, C.; Jiang, T.; Qin, S.; Zhang, W.; Cao, Y.; Hu, C.; Zhang, F.; Qiao, D.; et al. Horizontal transfer of a novel soil agarase gene from marine bacteria to soil bacteria via human microbiota. Sci. Rep. 2016, 6, 34103.
  355. Pudlo, N.A.; Pereira, G.V.; Parnami, J.; Cid, M.; Markert, S.; Tingley, J.P.; Unfried, F.; Ali, A.; Campbell, A.; Urs, K.; et al. Extensive transfer of genes for edible seaweed digestion from marine to human gut bacteria. bioRxiv 2020, 2020.06.10.142968.
  356. Hehemann, J.-H.; Correc, G.; Barbeyron, T.; Helbert, W.; Czjzek, M.; Michel, G. Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota. Nature 2010, 464, 908–912.
  357. Thomas, F.; Barbeyron, T.; Tonon, T.; Génicot, S.; Czjzek, M.; Michel, G. Characterization of the first alginolytic operons in a marine bacterium: From their emergence in marine Flavobacteriia to their independent transfers to marine Proteobacteria and human gut Bacteroides. Environ. Microbiol. 2012, 14, 2379–2394.
  358. Baldrick, F.R.; McFadden, K.; Ibars, M.; Sung, C.; Moffatt, T.; Megarry, K.; Thomas, K.; Mitchell, P.; Wallace, J.M.; Pourshahidi, L.K.; et al. Impact of a (poly) phenol-rich extract from the brown algae Ascophyllum nodosum on DNA damage and antioxidant activity in an overweight or obese population: A randomized controlled trial. Am. J. Clin. Nutr. 2018, 108, 688–700.
  359. D’Archivio, M.; Filesi, C.; Varì, R.; Scazzocchio, B.; Masella, R. Bioavailability of the polyphenols: Status and controversies. Int. J. Mol. Sci. 2010, 11, 1321–1342.
  360. Sęczyk, Ł.; Świeca, M.; Kapusta, I.; Gawlik-Dziki, U. Protein-phenolic interactions as a factor affecting the physicochemical properties of white bean proteins. Molecules 2019, 24, 408.
  361. Buitimea-Cantúa, N.E.; Gutiérrez-Uribe, J.A.; Serna-Saldívar, S.O. Phenolic–protein interactions: Effects on food properties and health benefits. J. Med. Food 2018, 21, 188–198.
  362. Zhang, Q.; Cheng, Z.; Wang, Y.; Fu, L. Dietary protein-phenolic interactions: Characterization, biochemical-physiological consequences, and potential food applications. Crit. Rev. Food Sci. Nutr. 2020, 1–27.
  363. Imbs, T.; Zvyagintseva, T. Phlorotannins are polyphenolic metabolites of brown algae. Russ. J. Mar. Biol. 2018, 44, 263–273.
  364. Zhang, H.; Yu, D.; Sun, J.; Liu, X.; Jiang, L.; Guo, H.; Ren, F. Interaction of plant phenols with food macronutrients: Characterisation and nutritional–physiological consequences. Nutr. Res. Rev. 2013, 27, 1–15.
  365. Mignet, N.; Seguin, J.; Chabot, G.G. Bioavailability of polyphenol liposomes: A challenge ahead. Pharmaceutics 2013, 5, 457–471.
  366. Jakobek, L.; Matić, P. Non-covalent dietary fiber-polyphenol interactions and their influence on polyphenol bioaccessibility. Trends Food Sci. Technol. 2019, 83, 235–247.
  367. Bohn, T. Dietary factors affecting polyphenol bioavailability. Nutr. Rev. 2014, 72, 429–452.
  368. Wojtunik-Kulesza, K.; Oniszczuk, A.; Oniszczuk, T.; Combrzyński, M.; Nowakowska, D.; Matwijczuk, A. Influence of in vitro digestion on composition, bioaccessibility and antioxidant activity of food polyphenols-a non-systematic review. Nutrients 2020, 12, 1401.
  369. Sookkasem, A.; Chatpun, S.; Yuenyongsawad, S.; Wiwattanapatapee, R. Alginate beads for colon specific delivery of self-emulsifying curcumin. J. Drug Deliv. Sci. Technol. 2015, 29, 159–166.
  370. Hussain, M.B.; Hassan, S.; Waheed, M.; Javed, A.; Farooq, M.A.; Tahir, A. Chapter 5-Bioavailability and metabolic pathway of phenolic compounds. In Plant Physiological Aspects of Phenolic Compounds; Soto-Hernández, M., Palma-Tenango, M., García-Mateos, R., Eds.; IntechOpen: Rijeka, Croatia, 2019.
  371. Luca, S.V.; Macovei, I.; Bujor, A.; Miron, A.; Skalicka-Woźniak, K.; Aprotosoaie, A.C.; Trifan, A. Bioactivity of dietary polyphenols: The role of metabolites. Crit. Rev. Food Sci. Nutr. 2020, 60, 626–659.
  372. Carregosa, D.; Carecho, R.; Figueira, I.; Santos, C.N. Low-molecular weight metabolites from polyphenols as effectors for attenuating neuroinflammation. J. Agric. Food Chem. 2020, 68, 1790–1807.
  373. Liu, Z.; Hu, M. Natural polyphenol disposition via coupled metabolic pathways. Expert Opin. Drug Metab. Toxicol. 2007, 3, 389–406.
  374. Suetsuna, K.; Maekawa, K.; Chen, J.-R. Antihypertensive effects of Undaria pinnatifida (wakame) peptide on blood pressure in spontaneously hypertensive rats. J. Nutr. Biochem. 2004, 15, 267–272.
  375. Pimenta, D.C.; Lebrun, I. Cryptides: Buried secrets in proteins. Peptides 2007, 28, 2403–2410.
  376. Hayes, M.; García-García, M.; Fitzgerald, C.; Lafarga, T. Chapter 27-Seaweed and milk derived bioactive peptides and small molecules in functional foods and cosmeceuticals. In Biotechnology of Bioactive Compounds: Sources and Applications; Gupta, V.K., Tuohy, M.G., Eds.; John Wiley & Sons: Oxford, UK, 2015; pp. 669–691.
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