The efect of commercial functional food with probiotics on microorganisms from early carious lesions

Caries rates in school-age children are still high enough to be the cause of serious concern for health systems in diferent countries. The biotechnology strategies studied to decrease these rates include the consumption of probiotics—available via a variety of functional foods obtainable on the mark...

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Autores:
Angarita‑Díaz, María del Pilar
Arias, Johanna C
Bedoya Correa, Claudia María
Cepeda, María J
Arboleda, María F
Chacón, Juan M
Leal, Yenny
Tipo de recurso:
Article of investigation
Fecha de publicación:
2020
Institución:
Universidad Cooperativa de Colombia
Repositorio:
Repositorio UCC
Idioma:
OAI Identifier:
oai:repository.ucc.edu.co:20.500.12494/46494
Acceso en línea:
https://hdl.handle.net/20.500.12494/46494
Palabra clave:
Alimentos funcionales
Probioticos
Caries
Functional food
Probiotics
Caries
Rights
openAccess
License
Atribución
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oai_identifier_str oai:repository.ucc.edu.co:20.500.12494/46494
network_acronym_str COOPER2
network_name_str Repositorio UCC
repository_id_str
dc.title.spa.fl_str_mv The efect of commercial functional food with probiotics on microorganisms from early carious lesions
title The efect of commercial functional food with probiotics on microorganisms from early carious lesions
spellingShingle The efect of commercial functional food with probiotics on microorganisms from early carious lesions
Alimentos funcionales
Probioticos
Caries
Functional food
Probiotics
Caries
title_short The efect of commercial functional food with probiotics on microorganisms from early carious lesions
title_full The efect of commercial functional food with probiotics on microorganisms from early carious lesions
title_fullStr The efect of commercial functional food with probiotics on microorganisms from early carious lesions
title_full_unstemmed The efect of commercial functional food with probiotics on microorganisms from early carious lesions
title_sort The efect of commercial functional food with probiotics on microorganisms from early carious lesions
dc.creator.fl_str_mv Angarita‑Díaz, María del Pilar
Arias, Johanna C
Bedoya Correa, Claudia María
Cepeda, María J
Arboleda, María F
Chacón, Juan M
Leal, Yenny
dc.contributor.author.none.fl_str_mv Angarita‑Díaz, María del Pilar
Arias, Johanna C
Bedoya Correa, Claudia María
Cepeda, María J
Arboleda, María F
Chacón, Juan M
Leal, Yenny
dc.subject.spa.fl_str_mv Alimentos funcionales
Probioticos
Caries
topic Alimentos funcionales
Probioticos
Caries
Functional food
Probiotics
Caries
dc.subject.other.spa.fl_str_mv Functional food
Probiotics
Caries
description Caries rates in school-age children are still high enough to be the cause of serious concern for health systems in diferent countries. The biotechnology strategies studied to decrease these rates include the consumption of probiotics—available via a variety of functional foods obtainable on the market— that are able to inhibit bacteria associated with this disease. In this vein, the purpose of this study was to determine the efect of these foods on the growth of microorganisms in early carious lesions in children aged between 6 and 12. In the frst phase, an agar well difusion method was applied to selected foods, available in supermarkets, which contain probiotics that have already been shown to inhibit Streptococcus mutans (ATCC 25175), and to lower the pH in liquid culture media. In a second phase, these foods (n= 4) were examined in terms of their ability to inhibit the microorganisms in contact with early carious lesions in children and to reduce the pH of mixed cultures combined with the food. The results revealed that, of the foods tested, three inhibit the growth of microorganisms in carious lesions and, at the same time, lower the pH of the culture by more than 2.5 units. The food with the highest inhibitory capacity (14 mm, IQR 13–14) showed a similar efect among patients (P> 0.05), which together with the fact that its sugar concentration is less than 10%, makes it an ideal candidate for clinical study.
publishDate 2020
dc.date.issued.none.fl_str_mv 2020-07
dc.date.accessioned.none.fl_str_mv 2022-09-23T17:37:04Z
dc.date.available.none.fl_str_mv 2022-09-23T17:37:04Z
dc.type.none.fl_str_mv Artículos Científicos
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dc.identifier.issn.spa.fl_str_mv 20452322
dc.identifier.uri.spa.fl_str_mv 10.1038/s41598-020-67775-z
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12494/46494
dc.identifier.bibliographicCitation.spa.fl_str_mv Angarita-Díaz, M.d., Arias, J.C., Bedoya-Correa, C. et al. The effect of commercial functional food with probiotics on microorganisms from early carious lesions. Sci Rep 10, 10732 (2020). https://doi.org/10.1038/s41598-020-67775-z
identifier_str_mv 20452322
10.1038/s41598-020-67775-z
Angarita-Díaz, M.d., Arias, J.C., Bedoya-Correa, C. et al. The effect of commercial functional food with probiotics on microorganisms from early carious lesions. Sci Rep 10, 10732 (2020). https://doi.org/10.1038/s41598-020-67775-z
url https://hdl.handle.net/20.500.12494/46494
dc.relation.isversionof.spa.fl_str_mv https://www.nature.com/articles/s41598-020-67775-z.pdf
dc.relation.ispartofjournal.spa.fl_str_mv Scientific Reports
dc.relation.references.spa.fl_str_mv World Health Organization. Oral Health. https://www.who.int/news-room/fact-sheets/detail/oral-health. Accessed 10 Sep 2019
Takahashi, N. & Nyvad, B. Te role of bacteria in the caries process: Ecological perspectives. J. Dent. Res. 90, 294–303 (2018).
World Health Organization (2015) Guideline: Sugars Intake for Adults and Children. Geneva: World Health Organization. https:// apps.who.int/iris/bitstream/handle/10665/149782/9789241549028_eng.pdf?sequence=1. Accessed 10 Sep 2019.
Boyce, W. T. et al. Social inequalities in childhood dental caries: Te convergent roles of stress, bacteria and disadvantage. Soc. Sci. Med. 71, 1644–1652 (2010).
Aldossary, M. S. et al. Prevalence of dental caries and dissure sealants in the frst permanent molars among male children in Riyadh, Kingdom Saudi Arabia. Int. J. Clin. Peiatr. Dent. 1, 365–370 (2018).
Ministry of Health of Colombia (2015) IV National Oral Health Study ENSAB IV. Bogotá: Minsalud. https://www.minsalud.gov. co/sites/rid/Lists/BibliotecaDigital/RIDE/VS/PP/ENSAB-IV-Situacion-Bucal-Actual.pdf. Accessed 28 Sep 2019
Hasler, C. & Brown, A. C. American dietetic association position of the American Dietetic Association: Functional foods. J. Am. Diet. Assoc. 109, 735–746 (2009)
van Loveren, C., Broukal, Z. & Oganessian, E. Functional foods/ingredients and dental caries. Eur. J. Nutr. 51, S15-25 (2012).
Food and Agriculture Organization of the United Nations, World Health Organization. Guidelines for the Evaluation of Probiotics in Food. London, Ontario, Canada, 2002. https://www.who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf. Accessed 15 Sep 2019
Lin, Y. T., Chou, C. C. & Hsu, C. Y. Efects of Lactobacillus casei Shirota intake on caries risk in children. J. Dent. Sci. 12, 179–184 (2017).
Näse, L. et al. Efect of long-term consumption of a probiotic bacterium, Lactobacillus rhamnosus GG, in milk on dental caries and caries risk in children. Caries Res. 35, 412–420 (2001)
Ahola, A. J. et al. Short-term consumption of probiotic-containing cheese and its efect on dental caries risk factors. Arch. Oral Biol. 47, 799–804 (2002).
Singh, R. P., Damle, S. G. & Chawla, A. Salivary mutans streptococci and lactobacilli modulations in young children on consumption of probiotic ice-cream containing Bifdobacterium lactis Bb12 and Lactobacillus acidophilus La5. Acta Odontol. Scand. 69, 389–394 (2011).
Ferrazzano, G. F., Cantile, T., Sangianantoni, G., Amato, I. & Ingenito, A. Te efects of short-term consumption of commercial yogurt on salivary mutans streptococci and lactobacilli counts: An in vivo investigation. Eur. J. Clin. Nutr. 65, 1170–1172 (2011).
Bhalla, M., Ingle, N. A., Kaur, N. & Yadav, P. Mutans streptococci estimation in saliva before and afer consumption of probiotic curd among school children. J. Int. Soc. Prev. Community Dent. 5, 31–34 (2015).
Ashwin, D. et al. Efect of probiotic containing ice cream on Salivary Mutans Streptococci (SMS) levels in children of 6–12 years of age: A randomized controlled double-blind study with six-months follow up. J. Clin. Diagn. Res. 9, 6–9 (2015).
Bafna, H. P. et al. Efect of short-term consumption of amul probiotic yogurt containing Lactobacillus acidophilus La5 and Bifdobacterium lactis Bb12 on salivary Streptococcus mutans count in high caries risk individuals. Int. J. Appl. Basic Med. Res. 8, 111–115 (2018)
Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard—Ninth Edition. CLSI document M07–A9 (Clinical and Laboratory Standards Institute, Wayne, 2012).
Téllez, M., Martignon, S., Cortés, A. P. & Gómez, H. F. Valoración individual de riesgo de caries con el Riesgograma. UstaSalud 8, 69–74 (2009).
Chilton, S., Burton, J. & Reid, G. Inclusion of fermented foods in food guides around the world. Nutrients 7, 390–404 (2015)
Ferrazzano, G. F. et al. Protective efect of yogurt extract on dental enamel demineralization in vitro. Aust. Dent. J. 53, 301–370 (2008).
Ghasempour, M. et al. Efect of milk and yogurt on streptococcus sobrinus counts and caries score in rats. Dent. Res. J. 12, 569–573 (2015).
Collins, E. B. & Aramaki, K. Production of hydrogen peroxide by Lactobacillus acidophilus. J. Dairy Sci. 63, 353–357 (1980).
Martinez, F. A. C., Balciunas, E. M., Converti, A., Cotter, P. D. & de Souza Oliveira, R. P. Bacteriocin production by Bifdobacterium spp. A review. Biotechnol. Adv. 31, 482–488 (2013).
Kabuki, T., Uenishi, H., Watanabe, M., Seto, Y. & Nakajima, H. Characterization of a bacteriocin, Termophilin 1277, produced by Streptococcus thermophilus SBT1277. J. Appl. Microbiol. 102, 971–980 (2007).
Mahmood, T., Masud, T., Ali, S., Abbasi, K. S. & Liaquat, M. Optimization and partial characterization of bacteriocin produced by Lactobacillus bulgaricus-TLBFT06 isolated from Dahi. Pak. J. Pharm. Sci. 28, 561–567 (2015).
Taipale, T., Pienihäkkinen, K., Salminen, S., Jokela, J. & Söderling, E. Bifdobacterium animalis subsp. lactis BB-12 administration in early childhood: a randomized clinical trial of efects on oral colonization by mutans streptococci and the probiotic. Caries Res. 46, 69–77 (2012)
Hasslof, P., West, C. E., Videhult, F. K., Brandelius, C. & Stecksen-Blicks, C. Early intervention with probiotic Lactobacillus paracasei F19 has no long-term efect on caries experience. Caries Res. 47, 559–565 (2013).
Petti, S., Tarsitani, G. & D’Arca, S. Antibacterial activity of yoghurt against viridans streptococci in vitro. Arch Oral. Biol. 53, 985–990 (2008).
Chapman, C. M., Gibson, G. R. & Rowland, I. Health benefts of probiotics: Are mixtures more efective than single strains?. Eur. J. Nutr. 50, 1–17 (2011).
Moore, B., Horti, A. & Fielding, B. Evaluation of the nutrient content of yogurts: A comprehensive survey of yogurt products in the major UK supermarkets. BMJ Open. 8, e021387 (2018).
Bintsis, T. Lactic acid bacteria as starter cultures: An update in their metabolism and genetics. AIMS Microbiol. 4, 665–684 (2018)
Angarita-Díaz, M. P. et al. Efects of a functional food supplemented with probiotics on biological factors related to dental caries in children: A pilot study. Eur. Arch. Paediatr. 21, 161–169 (2019).
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spelling Angarita‑Díaz, María del PilarArias, Johanna CBedoya Correa, Claudia MaríaCepeda, María JArboleda, María FChacón, Juan MLeal, Yenny102022-09-23T17:37:04Z2022-09-23T17:37:04Z2020-072045232210.1038/s41598-020-67775-zhttps://hdl.handle.net/20.500.12494/46494Angarita-Díaz, M.d., Arias, J.C., Bedoya-Correa, C. et al. The effect of commercial functional food with probiotics on microorganisms from early carious lesions. Sci Rep 10, 10732 (2020). https://doi.org/10.1038/s41598-020-67775-zCaries rates in school-age children are still high enough to be the cause of serious concern for health systems in diferent countries. The biotechnology strategies studied to decrease these rates include the consumption of probiotics—available via a variety of functional foods obtainable on the market— that are able to inhibit bacteria associated with this disease. In this vein, the purpose of this study was to determine the efect of these foods on the growth of microorganisms in early carious lesions in children aged between 6 and 12. In the frst phase, an agar well difusion method was applied to selected foods, available in supermarkets, which contain probiotics that have already been shown to inhibit Streptococcus mutans (ATCC 25175), and to lower the pH in liquid culture media. In a second phase, these foods (n= 4) were examined in terms of their ability to inhibit the microorganisms in contact with early carious lesions in children and to reduce the pH of mixed cultures combined with the food. The results revealed that, of the foods tested, three inhibit the growth of microorganisms in carious lesions and, at the same time, lower the pH of the culture by more than 2.5 units. The food with the highest inhibitory capacity (14 mm, IQR 13–14) showed a similar efect among patients (P> 0.05), which together with the fact that its sugar concentration is less than 10%, makes it an ideal candidate for clinical study.https://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=00016517480000-0001-5987-398Xmaria.angaritad@campusucc.edu.coclaudia.bedoyac@campusucc.edu.cohttps://scholar.google.com/citations?user=8HBl_VIAAAAJ&hl=es10Universidad Cooperativa de Colombia, Medellín. OdontologíaNature Publishing GroupOdontologíaMedellínhttps://www.nature.com/articles/s41598-020-67775-z.pdfScientific ReportsWorld Health Organization. Oral Health. https://www.who.int/news-room/fact-sheets/detail/oral-health. Accessed 10 Sep 2019Takahashi, N. & Nyvad, B. Te role of bacteria in the caries process: Ecological perspectives. J. Dent. Res. 90, 294–303 (2018).World Health Organization (2015) Guideline: Sugars Intake for Adults and Children. Geneva: World Health Organization. https:// apps.who.int/iris/bitstream/handle/10665/149782/9789241549028_eng.pdf?sequence=1. Accessed 10 Sep 2019.Boyce, W. T. et al. Social inequalities in childhood dental caries: Te convergent roles of stress, bacteria and disadvantage. Soc. Sci. Med. 71, 1644–1652 (2010).Aldossary, M. S. et al. Prevalence of dental caries and dissure sealants in the frst permanent molars among male children in Riyadh, Kingdom Saudi Arabia. Int. J. Clin. Peiatr. Dent. 1, 365–370 (2018).Ministry of Health of Colombia (2015) IV National Oral Health Study ENSAB IV. Bogotá: Minsalud. https://www.minsalud.gov. co/sites/rid/Lists/BibliotecaDigital/RIDE/VS/PP/ENSAB-IV-Situacion-Bucal-Actual.pdf. Accessed 28 Sep 2019Hasler, C. & Brown, A. C. American dietetic association position of the American Dietetic Association: Functional foods. J. Am. Diet. Assoc. 109, 735–746 (2009)van Loveren, C., Broukal, Z. & Oganessian, E. Functional foods/ingredients and dental caries. Eur. J. Nutr. 51, S15-25 (2012).Food and Agriculture Organization of the United Nations, World Health Organization. Guidelines for the Evaluation of Probiotics in Food. London, Ontario, Canada, 2002. https://www.who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf. Accessed 15 Sep 2019Lin, Y. T., Chou, C. C. & Hsu, C. Y. Efects of Lactobacillus casei Shirota intake on caries risk in children. J. Dent. Sci. 12, 179–184 (2017).Näse, L. et al. Efect of long-term consumption of a probiotic bacterium, Lactobacillus rhamnosus GG, in milk on dental caries and caries risk in children. Caries Res. 35, 412–420 (2001)Ahola, A. J. et al. Short-term consumption of probiotic-containing cheese and its efect on dental caries risk factors. Arch. Oral Biol. 47, 799–804 (2002).Singh, R. P., Damle, S. G. & Chawla, A. Salivary mutans streptococci and lactobacilli modulations in young children on consumption of probiotic ice-cream containing Bifdobacterium lactis Bb12 and Lactobacillus acidophilus La5. Acta Odontol. Scand. 69, 389–394 (2011).Ferrazzano, G. F., Cantile, T., Sangianantoni, G., Amato, I. & Ingenito, A. Te efects of short-term consumption of commercial yogurt on salivary mutans streptococci and lactobacilli counts: An in vivo investigation. Eur. J. Clin. Nutr. 65, 1170–1172 (2011).Bhalla, M., Ingle, N. A., Kaur, N. & Yadav, P. Mutans streptococci estimation in saliva before and afer consumption of probiotic curd among school children. J. Int. Soc. Prev. Community Dent. 5, 31–34 (2015).Ashwin, D. et al. Efect of probiotic containing ice cream on Salivary Mutans Streptococci (SMS) levels in children of 6–12 years of age: A randomized controlled double-blind study with six-months follow up. J. Clin. Diagn. Res. 9, 6–9 (2015).Bafna, H. P. et al. Efect of short-term consumption of amul probiotic yogurt containing Lactobacillus acidophilus La5 and Bifdobacterium lactis Bb12 on salivary Streptococcus mutans count in high caries risk individuals. Int. J. Appl. Basic Med. Res. 8, 111–115 (2018)Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard—Ninth Edition. CLSI document M07–A9 (Clinical and Laboratory Standards Institute, Wayne, 2012).Téllez, M., Martignon, S., Cortés, A. P. & Gómez, H. F. Valoración individual de riesgo de caries con el Riesgograma. UstaSalud 8, 69–74 (2009).Chilton, S., Burton, J. & Reid, G. Inclusion of fermented foods in food guides around the world. Nutrients 7, 390–404 (2015)Ferrazzano, G. F. et al. Protective efect of yogurt extract on dental enamel demineralization in vitro. Aust. Dent. J. 53, 301–370 (2008).Ghasempour, M. et al. Efect of milk and yogurt on streptococcus sobrinus counts and caries score in rats. Dent. Res. J. 12, 569–573 (2015).Collins, E. B. & Aramaki, K. Production of hydrogen peroxide by Lactobacillus acidophilus. J. Dairy Sci. 63, 353–357 (1980).Martinez, F. A. C., Balciunas, E. M., Converti, A., Cotter, P. D. & de Souza Oliveira, R. P. Bacteriocin production by Bifdobacterium spp. A review. Biotechnol. Adv. 31, 482–488 (2013).Kabuki, T., Uenishi, H., Watanabe, M., Seto, Y. & Nakajima, H. Characterization of a bacteriocin, Termophilin 1277, produced by Streptococcus thermophilus SBT1277. J. Appl. Microbiol. 102, 971–980 (2007).Mahmood, T., Masud, T., Ali, S., Abbasi, K. S. & Liaquat, M. Optimization and partial characterization of bacteriocin produced by Lactobacillus bulgaricus-TLBFT06 isolated from Dahi. Pak. J. Pharm. Sci. 28, 561–567 (2015).Taipale, T., Pienihäkkinen, K., Salminen, S., Jokela, J. & Söderling, E. Bifdobacterium animalis subsp. lactis BB-12 administration in early childhood: a randomized clinical trial of efects on oral colonization by mutans streptococci and the probiotic. Caries Res. 46, 69–77 (2012)Hasslof, P., West, C. E., Videhult, F. K., Brandelius, C. & Stecksen-Blicks, C. Early intervention with probiotic Lactobacillus paracasei F19 has no long-term efect on caries experience. Caries Res. 47, 559–565 (2013).Petti, S., Tarsitani, G. & D’Arca, S. Antibacterial activity of yoghurt against viridans streptococci in vitro. Arch Oral. Biol. 53, 985–990 (2008).Chapman, C. M., Gibson, G. R. & Rowland, I. Health benefts of probiotics: Are mixtures more efective than single strains?. Eur. J. Nutr. 50, 1–17 (2011).Moore, B., Horti, A. & Fielding, B. Evaluation of the nutrient content of yogurts: A comprehensive survey of yogurt products in the major UK supermarkets. BMJ Open. 8, e021387 (2018).Bintsis, T. Lactic acid bacteria as starter cultures: An update in their metabolism and genetics. AIMS Microbiol. 4, 665–684 (2018)Angarita-Díaz, M. P. et al. Efects of a functional food supplemented with probiotics on biological factors related to dental caries in children: A pilot study. Eur. Arch. Paediatr. 21, 161–169 (2019).Alimentos funcionalesProbioticosCariesFunctional foodProbioticsCariesThe efect of commercial functional food with probiotics on microorganisms from early carious lesionsArtículos Científicoshttp://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAtribucióninfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2PublicationORIGINAL2020. The efect of commercial functional food with probiotics on microorganisms from early carious lesions.pdf2020. 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The efect of commercial functional food with probiotics on microorganisms from early carious lesions.pdf.txtExtracted texttext/plain42086https://repository.ucc.edu.co/bitstreams/dc934127-9798-43b3-8a09-41559ee8a931/downloadb3833776d4f2770f00fe7f0332382138MD5420.500.12494/46494oai:repository.ucc.edu.co:20.500.12494/464942024-08-10 20:57:25.105open.accesshttps://repository.ucc.edu.coRepositorio Institucional Universidad Cooperativa de Colombiabdigital@metabiblioteca.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