The practice of application and features of the control of oligosaccharides in the production of specialized food products. A review

Functional oligosaccharides include various  groups  of carbohydrates with  the  biological activity — an  ability  to modulate gut microbiota due to the  prebiotic, anti-adhesive and anti-inflammatory activities. The unique properties of oligosaccharides explain a wide spectrum of their use in the dairy industry: from food ingredients for imitation  of the  prebiotic activity of human milk oligosaccharides in infant dry milk mixtures to structuring additives, replacers of sugar and fat. When choosing oligosaccharides for inclusion into dairy products, their biological activity and technological properties that depend on a source  and method for extraction of these compounds are assessed. Fructooligosaccharides, galactooligosaccharides, xylooligosaccharides and pectic  oligosaccharides have been  most widely used. When developing recipes of products with stated biological effectiveness, it is necessary to remember that consumption of large  amounts of substances with prebiotic properties can lead to the  gastrointestinal disorder, which requires introducing into  practice the control of the oligosaccharide quantitative content in the product composition. The aim of this  review is analysis of possibilities of using  oligosaccharides in production of specialized  milk-based food products and  methods for controlling quality, safety  and  effectiveness of inclusion of such products into  a diet. The review considers the  existing methods for quantitative identification of oligosaccharides included in the composition of dairy products as functional ingredients. The emphasis is made on the limitations of the introduction of the developed analytical methods into  routine practice of the oligosaccharide control, which is linked with the complexity and multicomponent nature of the food matrix under study. The necessity of the further improvement of methods for quantitative identification of functional oligosaccharides in foods is shown.

1. Gibson, G. R., Hutkins, R., Sanders, M. E., Prescott, S. L., Reimer, R. A., Salminen, S. J. et al. (2017). Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nature Reviews Gastroenterology & Hepatology, 14, 491–502. https://doi.org/10.1038/nrgastro.2017.75

2. Oliveira, D. L., Wilbey, R. A., Grandison, A. S., Roseiro, L. B. (2015). Milk oligosaccharides: A review. International Journal Dairy Technology, 68(3), 305–321. https://doi.org/10.1111/1471–0307.12209

3. Meyrand, M., Dallas, D. C., Caillat, H., Bouvier, F., Martin, P., Barile, D. (2013) Comparison of milk oligosaccharides between goats with and without the genetic ability to synthesize αs1-casein. Small Ruminant Research, 113(2–3), 411–420. https://doi.org/10.1016/j.smallrumres.2013.03.014

4. Van Laere, K. M. J., Hartemink, R., Bosveld, M., Schols, H. A., Voragen, A. G. J. (2000). Fermentation of plant cell wall derived polysaccharides and their corresponding oligosaccharides by intestinal bacteria. Journal Agriculture Food Chemistry, 48(5), 1644–1652. https://doi.org/10.1021/jf990519i

5. Braga, A., Gomes, D., Rainha, J., Cardoso, B. B., Amorim, C., Silvério, S. C. et al. (2022). Tailoring fructooligosaccharides composition with engineered Zymomonas mobilis ZM4. Applied Microbiology and Biotechnology, 106(12), 4617–4626. https://doi.org/10.1007/s00253–022–12037–3

6. Carneiro, S. B., Duarte, F. I. C., Heimfarth, L., Quintans, J. S. S., Quintans-Júnior, L. J., da Veiga Júnior, V. F. (2019). Cyclodextrin–drug inclusion complexes: In vivo and In vitro approaches. International Journal of Molecular Sciences, 20(3), Article 642. https://doi.org/10.3390/ijms20030642

7. Ibrahim, O. O. (2018). Functional oligosaccharides: Chemicals structure, manufacturing, health benefits, applications and regulations. Journal of Food Chemistry & Nanotechnology, 4(4), 65–76. https://doi.org/10.17756/jfcn.2018–060

8. Teng, P.-Y., Kim, W. K. (2018). Review: Roles of prebiotics in intestinal ecosystem of broilers. Frontiers in Veterinary Science, 5, Article 245. https://doi.org/10.3389/fvets.2018.00245

9. Daniels, B., Coutsoudis, A., Autran, C., Mansen, K.A., Israel-Ballard, K., Bode, L. (2017). The effect of simulated flash heating pasteurisation and Holder pasteurisation on human milk oligosaccharides. Paediatrics and International Child Health, 37(3), 204–209. https://doi.org/10.1080/20469047.2017.1293869

10. González-Delgado I., López-Muñoz M.-J., Morales G., Segura Y. (2016). Optimisation of the synthesis of high galacto-oligosaccharides (GOS) from lactose with β-galactosidase from Kluyveromyces lactis. International Dairy Journal, 61, 211–219. https://doi.org/10.1016/j.idairyj.2016.06.007

11. Guimarães, J. T., Silva, E. K., Arruda, H. S., Freitas M. Q., Pastore G. M., Meireles M. A. A. et al. (2020). How does the degree of inulin polymerization affect the bioaccessibility of bioactive compounds from soursop whey beverage during in vitro gastrointestinal digestion? Food Hydrocolloids, 101, Article 105511. https://doi.org/10.1016/j.foodhyd.2019.105511

12. De Paulo Farias, D., de Araújo, F. F., Neri-Numa, I. A., Pastore, G. M. (2019). Prebiotics: Trends in food, health and technological applications. Trends in Food Science & Technology, 93, 23–35. https://doi.org/10.1016/j.tifs.2019.09.004

13. Leddomado, L. S., Silva, R., Guimarães, J. T., Balthazar, C. F., Ramos, G. L. P. A., Freitas, M. Q. et al. (2021). Technological benefits of using inulin and xylooligosaccharide in dulce de leche. Food Hydrocolloids, 110, Article 106158. https://doi.org/10.1016/j.foodhyd.2020.106158

14. Saad, N., Delattre, C., Urdaci, M., Schmitter, J. M., Bressollier, P. (2013). An overview of the last advances in probiotic and prebiotic field. LWT — Food Science and Technology, 50(1), 1–16. https://doi.org/10.1016/j.lwt.2012.05.014

15. Wilson, B., Whelan, K. (2017). Prebiotic inulin-type fructans and galactooligosaccharides: definition, specificity, function, and application in gastrointestinal disorders. Journal of Gastroenterology and Hepatology, 32(Suppl 1), 64–68. https://doi.org/10.1111/jgh.13700

16. Nieto-Domínguez, M., de Eugenio, L. I., York-Durán, M. J., Rodríguez-Colinas, B., Plou, F. J., Chenoll, E. et al. (2017). Prebiotic effect of xylooligosaccharides produced from birchwood xylan by a novel fungal GH11 xylanase. Food Chemistry, 232, 105–113. https://doi.org/10.1016/j.foodchem.2017.03.149

17. de Freitas, C., Terrone, C. C., Forsan, C. F., Milagres, A. M. F., Brienzo, M. (2022). Oligosaccharides from Lignocellulosic Biomass and Their Biological and Physicochemical Properties. Chapter in a book: Hemicellulose Biorefinery: A Sustainable Solution for Value Addition to Bio-Based Products and Bioenergy. Clean Energy Production Technologies. Springer, Singapore. https://doi.org/10.1007/978–981–16–3682–0_9

18. Closa-Monasterolo, R., Gispert-Llaurado, M., Luque, V., Ferre, N., Rubio-Torrents, C., Zaragoza-Jordana, M. et al. (2013). Safety and efficacy of inulin and oligofructose supplementation in infant formula: results from a randomized clinical trial. Clinical Nutrition, 32(6), 918–927. DOI: 10.1016/j.clnu.2013.02.009

19. Mensink, M. A., Frijlink, H. W., van der Voort Maarschalk, K., Hinrichs, W. L. J. (2015). Inulin, a flexible oligosaccharide I: Review of its physicochemical characteristics. Carbohydrate Polymers, 130, 405–419. DOI:10.1016/j.carbpol.2015.05.02651

20. Babbar, N., Baldassarre, S., Maesen, M., Prandi, B., Dejonghe, W., Sforza, S. et al. (2016). Enzymatic production of pectic oligosaccharides from onion skins. Carbohydrate Polymers, 146, 245–252. https://doi.org/10.1016/j.carbpol.2016.03.011

21. Moreno, F. J., Corzo, N., Montilla, A., Villamiel, M., Olano, A. (2017). Current state and latest advances in the concept, production and functionality of prebiotic oligosaccharides. Current Opinion in Food Science, 13, 50–55. https://doi.org/10.1016/j.cofs.2017.02.009

22. Balthazar, C. F., Silva, H. L. A., Vieira, A. H., Neto, R. P. C., Cappato, L. P., Coimbra, P. T. et al. (2017). Assessing the effects of different prebiotic dietary oligosaccharides in sheep milk ice cream. Food Research International, 91, 38–46. https://doi.org/10.1016/j.foodres.2016.11.008

23. Singh, S. P., Jadaun, J. S., Narnoliya, L. K., Pandey, A. (2017). Prebiotic oligosaccharides: Special focus on fructooligosaccharides, Its biosynthesis and bioactivity. Applied Biochemistry and Biotechnology, 183(2), 613–635. https://doi.org/10.1007/s12010–017–2605–2

24. Sánchez-Martínez, M. J., Soto-Jover, S., Antolinos, V., Martínez-Hernández, G.B., López-Gómez, A. (2020). Manufacturing of short-chain fructooligosaccharides: From laboratory to industrial scale. Food Engineering Reviews, 12, 149–172. https://doi.org/10.1007/s12393–020–09209–0

25. Chanalia, P., Gandhi, D., Attri, P., Dhanda, S. (2018). Purification and characterization of β-galactosidase from probiotic Pediococcus acidilactici and its use in milk lactose hydrolysis and galactooligosaccharide synthesis. Bioorganic Chemistry, 77, 176–189. https://doi.org/10.1016/j.bioorg.2018.01.006

26. Sabater, C., Olano, A., Corzo, N., Montilla, A. (2019). GC–MS characterisation of novel artichoke (Cynara scolymus) pectic-oligosaccharides mixtures by the application of machine learning algorithms and competitive fragmentation modelling. Carbohydrate Polymers, 205, 513–523. https://doi.org/10.1016/j.carbpol.2018.10.054

27. Fehlbaum, S., Prudence, K., Kieboom, J., Heerikhuisen, M., van den Broek, T., Schuren, F. H. J. et al. (2018). In vitro fermentation of selected prebiotics and their effects on the composition and activity of the adult gut microbiota. International Journal of Molecular Sciences, 19(10), Article 3097. https://doi.org/10.3390/ijms19103097

28. Lin, S., Mao, S., Guan, Y., Luo, L., Luo, L., Pan, Y. (2012). Effects of dietary chitosan oligosaccharides and Bacillus coagulans on the growth, innate immunity and resistance of koi (Cyprinus carpio koi). Aquaculture, 342–343, 36–41. https://doi.org/10.1016/j.aquaculture.2012.02.009

29. den Ende, W. V. (2013). Multifunctional fructans and raffinose family oligosaccharides. Frontiers in Plant Science, 4, Article 247. https://doi.org/10.3389/fpls.2013.00247

30. Sengupta, S., Mukherjee, S., Basak, P., Majumder, A. L. (2015). Significance of galactinol and raffinose family oligosaccharide synthesis in plants. Frontiers in Plant Science, 6, Article 656. https://doi.org/10.3389/fpls.2015.00656

31. Davis, J. C. C., Lewis, Z. T., Krishnan, S., Bernstein, R. M., Moore, S. E., Prentice A. M. et al. (2017). Growth and morbidity of gambian infants are influenced by maternal milk oligosaccharides and infant gut microbiota. Scientific Reports, 7, Article 40466. https://doi.org/10.1038/srep40466

32. Bych, K., Mikš, M. H., Johanson, T., Hederos, M. J., Vigsnaes, L. K., Becker, P. (2019). Production of HMOs using microbial hosts — from cell engineering to large scale production. Current Opinion in Biotechnology, 56, 130–137. https://doi.org/10.1016/j.copbio.2018.11.003

33. Weinborn, V., Li, Y., Shah, I. M., Yu, H., Dallas, D. C., German, J. B. et al. (2020). Production of functional mimics of human milk oligosaccharides by enzymatic glycosylation of bovine milk oligosaccharides. International Dairy Journal, 102, Article 104583. https://doi.org/10.1016/j.idairyj.2019.104583

34. Bering, S. B. (2018). Human milk oligosaccharides to prevent gut dysfunction and necrotizing enterocolitis in preterm neonates. Nutrients, 10(10), Article 1461. https://doi.org/10.3390/nu10101461

35. Blanco-Morales, V., López-García, G., Cilla, A., Garcia-Llatas, G., Barberá, R., Lagarda, M. J. et al. (2018). The impact of galactooligosaccharides on the bioaccessibility of sterols in a plant sterol-enriched beverage: adaptation of the harmonized INFOGEST digestion method. Food & Function, 9(4), 2080–2089. https://doi.org/10.1039/c8fo00155c

36. Lin, H., Li, S., Xu, C., Pang, M., Wang, S. (2018). Simultaneous determination of galactose, glucose, lactose and galactooligosaccharides in galactooligosaccharides raw materials by high-performance anion-exchange chromatography with pulsed amperometric detection. Food Chemistry, 263, 29–36. https://doi.org/10.1016/j.foodchem.2018.04.092

37. Zhuang, D., Qin, J., Wang, H.-Y., Zhang, Y., Liu, C.-Y., Ding, Q.-Q. et al. (2019). Oligosaccharide-based quality evaluation of Atractylodis rhizome and a strategy for simplifying its quality control. BMC Chemistry, 13(1), Article 92. https://doi.org/10.1186/s13065–019–0605–8

38. Li, F., Wang, H., Xin, H., Cai, J., Fu, Q., Jin, Y. (2016). Development, validation and application of a hydrophilic interaction liquid chromatography-evaporative light scattering detection based method for process control of hydrolysis of xylans obtained from different agricultural wastes. Food Chemistry, 212, 155–161. https://doi.org/10.1016/j.foodchem.2016.05.118

39. Rodríguez-Gómez, R., Jiménez-Díaz, I., Zafra-Gómez, A., Morales, J.C. (2015). Improved sample treatment for the determination of fructooligosaccharides in milk related products by liquid chromatography with electrochemical and refractive index detection. Talanta, 144, 883–889. https://doi.org/10.1016/j.talanta.2015.07.042

40. Alfonso-Muniozguren, P., Serna-Galvis, E. A., Bussemaker, M., Torres-Palma, R. A., Lee, J. (2021). A review on pharmaceuticals removal from waters by single and combined biological, membrane filtration and ultra-sound systems. Ultrasonics Sonochemistry, 76, Article 105656. https://doi.org/10.1016/j.ultsonch.2021.105656

41. Sousa, Y. R. F., Araújo, D. F. S., Pulido, J. O., Pintado, M. M. E., Martínez-Férez, A., Queiroga, R. C. R. E. (2019). Composition and isolation of goat cheese whey oligosaccharides by membrane technology. International Journal of Biological Macromolecules, 139, 57–62. https://doi.org/10.1016/j.ijbiomac.2019.07.181

42. Zaky, A. S., Pensupa, N., Andrade-Eiroa, Á., Tucker, G. A., Du, C. (2017). A new HPLC method for simultaneously measuring chloride, sugars, organic acids and alcohols in food samples. Journal of Food Composition and Analysis, 56, 25–33. https://doi.org/10.1016/j.jfca.2016.12.010

43. Wang, R., Chen, Z. (2017). A covalent organic framework-based magnetic sorbent for solid phase extraction of polycyclic aromatic hydrocarbons, and its hyphenation to HPLC for quantitation. Microchimica Acta, 184, 3867–3874. https://doi.org/10.1007/s00604–017–2408–8

44. Galant, A. L., Kaufman, R. C., Wilson, J. D. (2015). Glucose: Detection and analysis. Food Chemistry, 188, 149–160. https://doi.org/10.1016/j.foodchem.2015.04.071

45. Hu, L.-J., Li, X.-F., Hu, J.-Q., Ni, X.-J., Lu, H.-Y., Wang, J.-J. et al. (2017). A Simple HPLC–MS/MS method for determination of tryptophan, kynurenine and kynurenic acid in human serum and its potential for monitoring antidepressant therapy. Journal of Analytical Toxicology, 41(1), 37–44. https://doi.org/10.1093/jat/bkw071

46. Christensen, A. S., Skov, S. H., Lendal, S. E., Hornshøj, B. H. (2020). Quantifying the human milk oligosaccharides 2’-fucosyllactose and 3-fucosyllactose in different food applications by high-performance liquid chromatography with refractive index detection. Journal of Food Science, 85(2), 332–339. https://doi.org/10.1111/1750–3841.15005

47. Jalaludin, I., Kim, J. (2021). Comparison of ultraviolet and refractive index detections in the HPLC analysis of sugars. Food Chemistry, 365, Article 130514. https://doi.org/10.1016/j.foodchem.2021.130514

48. Downes, K., Terry, L. A. (2010). A new acetonitrile-free mobile phase method for LC–ELSD quantification of fructooligosaccharides in onion. Talanta, 82(1), 118–124. https://doi.org/10.1016/j.talanta.2010.04.003

49. Hao, Q., Nan, T., Zhou, L., Kang, L., Guo, L., Yu, Y. (2019). Rapid simultaneous quantification of fructooligosaccharides in Morinda officianalis by ultra-high performance liquid chromatography. Journal of Separation Science, 42(13), 2222–2223. https://doi.org/10.1002/jssc.201801287

50. Charoenwongpaiboon, T., Sitthiyotha, T., Na Ayutthaya, P. P., Wangpaiboon, K., Chunsrivirot, S., Prousoontorn, M. H. et al. (2019). Modulation of fructooligosaccharide chain length and insight into the product binding motif of Lactobacillus reuteri 121 inulosucrase. Carbohydrate Polymers, 209, 111–121. https://doi.org/10.1016/j.carbpol.2018.12.078

51. Cürten, C., Anders, N., Juchem, N., Ihling, N., Volkenborn, K., Knapp, A. et al. (2017). Fast automated online xylanase activity assay using HPAEC-PAD. Analytical and Bioanalytical Chemistry, 410, 57–69. https://doi.org/10/1007/s00216–017–0712–0

52. Castells, C. B., Arias, V. C., Castells, R. C. (2012). Precolumn derivatization of reducing carbohydrates with 4-(3-Methyl-5-oxo-2-pyrazolin-1-yl) benzoic acid. Study of reaction, high-performance liquid chromatographic separation and quantitative performance of method. Chromatographia, 56(3–4), Article 153. https://doi.org/10.1007/BF02493204

53. Kurzyna-Szklarek, M., Cybulska, J., Zdunek, A. (2022). Analysis of the chemical composition of natural carbohydrates — An overview of methods. Food Chemistry, 394, Article 133466. https://doi.org/10.1016/j.foodchem.2022.133466

54. Lee, H., Cuthbertson, D. J., Otter, D. E., Barile, D. (2016). Rapid screening of bovine milk oligosaccharides in a whey permeate product and domestic animal milks by accurate mass database and tandem mass spectral library. Journal Agriculture Food Chemistry, 64(32), 6364–6374

55. Kailemia, M. J., Ruhaak, L. R., Lebrilla, C. B., Amster, I. J. (2014). Oligosaccharide analysis by mass spectrometry: A review of recent developments. Analytical Chemistry, 86(1), 196–212. https://doi.org/10.1021/ac403969n

56. Wang, J., Zhao, J., Nie, S., Xie, M., Li, S. (2022). MALDI mass spectrometry in food carbohydrates analysis: A review of recent researches. Food Chemistry, 399, Article 133968. https://doi.org/10.1016/j.foodchem.2022.133968

57. Qu, L., Jiang, Y., Huang, X., Cui, M., Ning, F., Liu, T. et al. (2019). High-throughput monitoring of multiclass syrup adulterants in honey based on the oligosaccharide and polysaccharide profiles by MALDI mass spectrometry. Journal of Agricultural and Food Chemistry, 67(40), 11256–11261. https://doi.org/10.1021/acs.jafc.9b05317

58. Sabater, C., Prodanov, M., Olano, A., Corzo, N., Montilla, A. (2016). Quantification of prebiotics in commercial infant formulas. Food Chemistry, 194, 6–11. https://doi.org/10.1016/j.foodchem.2015.07.127

59. Hiltunen, S., Sirén, H., Heiskanen, I., Backfolk, K. (2016). Capillary electrophoretic profiling of wood-based oligosaccharides. Cellulose, 23, 3331–3340. https://doi.org/10.1007/s10570–016–1011–1