Geleneksel Türk Yoğurtlarından İzole Edilen Lactobacillus delbrueckii subsp. bulgaricus ve Streptococcus thermophilus Bakterilerinde İntra-/Ekstrasellüler Folat Üretimi
Yıl 2024,
, 704 - 717, 30.06.2024
Meryem Nur Zeydanlı
,
Zehranur Yuksekdag
,
Berat Çınar Acar
Öz
Bu çalışmada, zengin folat içerikli yoğurt yapımında starter kültür olarak kullanılabilecek bakterilerin araştırılması hedeflenmiştir. Bu amaçla Türkiye’nin çeşitli ilçelerindeki geleneksel yöntemlerle yapılan yoğurtlardan 31 Lactobacillus spp. ve 32 Streptococcus spp. olmak üzere toplam 63 bakteri izole edilmiştir. Elde edilen bakterilerin API 50 CH kiti ile biyokimyasal tanımlaması gerçekleştirilmiştir. Tesadüfen seçilen 4 Laktobasil ve 4 Streptokok izolatının 16S rDNA gen bölgesi ile moleküler tanımlaması gerçekleştirilmiştir. Folat içermeyen kültür ortamı (FACM), skimmilk ve MRS/Elliker besi ortamlarında üç farklı tampon uygulamasında (potasyum fosfat, sodyum fosfat ve sodyum asetat) bakterilerin hücre içi ve hücre dışı folat üretim miktarları tespit edilmiştir. Kullanılan besiyerleri ve tampon çözeltiler arasında anlamlı bir farklılık olup olmadığı istatistiksel olarak incelenmiştir. Skimmilk besiyerinde potasyum fosfat tamponu uygulamasında, Lactobacillus delbrueckii subsp. bulgaricus ZN1181 suşu 105,6 µg/L değeri ile en yüksek intrasellüler folat üretimine sahip olduğu tespit edilirken, Streptococcus thermophilus Z651 suşu FACM besiyeri ve potasyum fosfat tamponunda en yüksek ekstrasellüler folat üretimi (79,9 µg/L) göstermiştir.
Destekleyen Kurum
Gazi Üniversitesi
Proje Numarası
05/2013-07
Teşekkür
Bu çalışma, Gazi Üniversitesi Fen Bilimleri Enstitüsü Biyoloji Anabilim Dalında, 2014 yılında tamamlanan “Geleneksel Yöntemlerle Yapılan Yoğurtlardan İzole Edilen Lactobacillus delbrueckii subsp. bulgaricus ve Streptococcus thermophilus Türlerinde Folat Üretimi” isimli yüksek lisans tezinden türetilmiştir. Ayrıca, çalışmamız Gazi Üniversitesi Bilimsel Araştırma Projeleri (BAP) Birimi tarafından 05/2013-07 kodlu proje ile desteklenmiştir.
Kaynakça
- Agagunduz, D., Sahin, T.O., Ayten, S., Yılmaz, B., Günesliol, B.E., Russo, P., Spano, G., & Ozogul, F. (2022). Lactic acid bacteria as pre-technological, bioprotective and health-promoting cultures in the dairy food industry. Food Bioscience, 47, 101617. https://doi.org/10.1016/j.fbio.2022.101617.
- Albano, C., Silvetti, T., & Brasca, M. (2020). Screening of lactic acid bacteria producing folate and their potential use as adjunct cultures for cheese bio-enrichment. FEMS Microbiology Letters, 367, 9. https://doi.org/10.1093/femsle/ fnaa059.
- Aras, Z. (2011). Rapid diagnostic methods in microbiology. Turk Hijyen ve Deneysel Biyoloji Dergisi, 68(2), 97–104.
- Aswathy, R.G., Ismail, B., John, R.P., & Nampoothiri, K.M. (2008). Evaluation of the probiotic characteristics of newly isolated lactic acid bacteria. Applied Biochemistry and Biotechnology, 151, 244-255. 10.1007/s12010-008-8183-6.
- Albano, C., Silvetti, T., & Brasca, M. (2020). Screening of lactic acid bacteria producing folate and their potential use as adjunct cultures for cheese bio-enrichment. FEMS Microbiology Letters, 367. https://doi.org/10.1093/femsle/ fnaa059.
- Albuquerque, M.A.C., Yamacita, D.S., Bedani, R., LeBlanc, J.G., & Saad, S.M.I. (2019). Influence of passion fruit by-product and fructooligosaccharides on the viability of Streptococcus thermophilus TH-4 and Lactobacillus rhamnosus LGG in folate bio-enriched fermented soy products and their effect on probiotic survival and folate bio-accessibility under in vitro simulated gastrointestinal conditions. International Journal of Food Microbiology, 292, 126-136. https://doi.org/10.1016/ j.ijfoodmicro.2018.12.012.
- Baggott J.E., Oster R.A., & Tamura T. (2012). Meta-analysis of cancer risk in folic acid supplementation trials. Cancer Epidemiology, 36, 78-81. 10.1016/j.canep.2011.05.003.
- Bailey S.W., & Ayling J.E. (2009). The extremely slow and variable activity of dihydrofolate reductase in the human liver and its implications for high folic acid intake. Proceedings of the National Academy Sciences of the USA, 106(36), 15424-9. 10.1073/pnas.0902072106.
- Cucick, A.C.C., Gianni, K., Todorov, S.D., de LeBlanc, A.M., LeBlanc, J., & Franco, B.D.G.M. (2020). Evaluation of the bioavailability and intestinal effects of milk fermented by folate producing lactic acid bacteria in a depletion/repletion mice model. Journal of Functional Foods, 66, 103785.
https://doi.org/10.1016/j.jff.2020.103785.
- Da Silva, F.F.P., Biscola, V., LeBlanc, J.G., & de Melo Franco, B.D.G. (2016). Effect of indigenous lactic acid bacteria isolated from goat milk and cheeses on folate and riboflavin content of fermented goat milk. LWT-Food Science and Technology, 71, 155-161. ISSN: 0023-6438.
- dos Santos, H.R.M., Argolo, C.S., Argolo-Filho, R.C., & Loguercio, L.L.A. (2019). 16S rDNA PCR based theoretical to actual delta approach on culturable mock communities revealed severe losses of diversity information. BMC Microbiology, 19, 74. https://doi.org/10.1186/s12866-019-1446-2.
- Engevik, M.A., Morra, C.N., Röth, D., Engevik, K., Spinler, J.K., Devaraj, S., Crawford, S.E., Estes, M.K., Kalkum, M., & Versalovic, J. (2019). Microbial metabolic capacity for ıntestinal folate production and modulation of host folate receptors. Frontiers in Microbiology Microbial Physiology and Metabolism, 10. https://doi.org/10.3389/ fmicb.2019.02305.
- Fayemi, O.E., Akanni, G.B., Sobowale, S.S., Oelofse, A., & Buys, E.M. (2023). Potential for increasing folate contents of traditional African fermented sorghum gruel (Motoho) using presumptive probiotic lactic acid bacteria. Journal of Food Composition and Analysis, 115, 104850. https://doi.org/10.1016/j.jfca.2022.104850.
- Frey, J., & Nicolet, J. (1997). Molecular identification and epidemiology of animal mycoplasmas. Wiener Klinische Wochenschrift, 109 (14-15), 600-603.
- Greppi, A., Hemery, Y., Berrazaga, I. Almaksour, Z., & Humblot, C. (2017). The ability of lactobacilli isolated from traditional cereal-based fermented food to produce folate in culture media under different growth conditions. LWT-Food Science and Technology, 86, 277-84. 10.1016/j.lwt. 2017.08.007.
- Haghshenas, B., Abdullah, N., Nami, Y., Radiah, D., Rosli, R., & Khosroushahi, A.Y. (2014). Different effects of two newly-isolated probiotic Lactobacillus plantarum 15HN and Lactococcus lactis subsp. lactis 44 Lac strains from traditional dairy products on cancer cell lines. Anaerobe, 30, 51-59. 10.1016/j.anaerobe.2014.08.009.
- Hildebrand, L.A., Dumas, B., Milrod, C.J., & Hudspeth, J.C. (2021). Folate deficiency in an urban safety-net population. The American Journal of Medicine, 134(10), 1265-1269.
https://doi.org/10.1016/j.amjmed.2021.04.028.
- Iyer, R., & Tomar, S.K. (2009). Folate: A functional food constituent. Journal of Food Science, 74(9), R114-R122. 10.1111/j.1750-3841.2009.01359.x.
- Khalili, M., Rad, AH., Khosroushahi, A.Y., Khosravi, H., & Jafarzadeh, S. (2020). Application of probiotics in folate bio-fortification of yoghurt. Probiotics and Antimicrobial Proteins, 12, 756-763. https://doi.org/10.1007/s12602-019-09560-7.
- Kızılyıldırım, S., Köksal, F. (2023). Investigation of the antibiotic profiles and phlogenetic relationships of the lactobacillus species ısolated from goat’s and cow’s milk. KSU Journal of Agriculture and Nature. 26 (5), 1021-1026. https://doi.org/10.18016/ksutarimdoga.vi.1178550.
- Laiño, J.E., LeBlanc, J.G., De Giori, & G.S. (2012). Production of natural folates by lactic acid bacteria starter cultures isolated from artisanal Argentinean yogurts. Canadian Journal of Microbiology, 58, 581-588. https://doi.org/10.1139/ w2012-026.
- LeBlanc, J.G., de Giori, G.S., Smid, E.J., Hugenholtz, J., & Sesma, F. (2007). Folate production by lactic acid bacteria and other food-grade microorganisms. Communicating Current Research and Educational Topics and Trends in Applied Microbiology, 1, 329-339.
- LeBlanc, J.G., Laino, J.E., del Valle, M.J., Vannini, V., van Sinderen, D., Taranto, M.P., de Valdez, G.F., de Giori, G.S., Sesma, F. (2011). B-Group vitamin production by lactic acid bacteria - current knowledge and potential applications. Journal of Applied Microbiology, 111(6), 1297-1309. 10.1111/j.1365-2672.2011.05157.x.
- Levit, R., Savoy de Giori, G., de Moreno de LeBlanc, A., & LeBlanc, J.G. (2021). Recent update on lactic acid bacteria producing riboflavin and folates: Application for food fortification and treatment of intestinal inflammation. Journal of Applied Microbiology, 130, 1412-1424. ISSN 1364-5072.
- Liu, M., Chen, Q., Su, Y., Zeng, L., Wu, H., Gu, Q., Ping Li, P., Mahara, F.A., Nuraida, L., & Lioe, H.N. (2021). Folate in milk is fermented by lactic acid bacteria from different food sources. Preventive Nutrition and Food Science, 26(2), 230-240. https://doi.org/10. 3746/pnf.2021.26.2.230 Rydon 2016.
- Mahara, F.A., Nuraida, L., & Lioe, H.N. (2021). Folate in milk is fermented by lactic acid bacteria from different food sources. Preventive Nutrition and Food Science, 26(2), 230–240. https://doi.org/ 10.3746/pnf.2021.26.2.230Rydon 2016.
- Meucci, A., Rossetti, L., Zago, M., Monti, L. Giraffa, G., Carminati, D., & Tidona, F. (2018). Folates biosynthesis by Streptococcus thermophilus during growth in milk. Food Microbiology, 69, 116-122. 10.1016/j.fm.2017.08.001.
Patel, J.B. (2001). 16S rRNA gene sequencing for bacterial pathogen identification in the clinical laboratory. Molecular Diagnosis, 6(4), 313-21. 10.1054/modi.2001.29158.
- Pompei, A., Cordisco, L., Amaretti, A., Zanoni, S., Raimondi, S., Matteuzzi, D., & Rossi, M. (2007). Administration of folate-producing Bifidobacteria enhances folate status in Wistar rats. Journal of Nutrition, 137(12), 2742–2746. 10.1093/jn/ 137.12.2742.
- Rad, A.H., Khosroushahi, A.Y., Khalili, M., & Jafarzadeh, S. (2016). Folate bio-fortification of yoghurt and fermented milk: A review. Dairy Science and Technology, 96(4), 427-441. 10.1007/s13594-016-0286-1.
- Rossi, M., Amaretti, A., & Raimondi, S. (2011). Folate production by probiotic bacteria. Nutrients, 3, 118-134. 10.3390/nu3010118.
- Saubade, F., Hemery, Y.M., Guyot, J.P., & Humblot, C. (2017). Lactic acid fermentation is a tool for increasing the folate content of foods. Critical Reviews in Food Science and Nutrition, 57(18), 3894-3910. 10.1080/10408398.2016.1192986.
- Sybesma, W., Starrenburg, M., Tijsseling, L., Hoefnagel, M.H.N., & Hugenholtz, J. (2003a). Effect of cultivation conditions on folate production by lactic acid bacteria. Applied and Environmental Microbiology, 69(8), 4542-4548. 10.1128/AEM.69.8. 4542-4548.2003.
- Sybesma, W., Starrenburg, M., Kleerebezem, M., Mierau, I., de Vos W.M., & Hugenholtz, J. (2003b). Increased production of folate by metabolic engineering of Lactococcus lactis. Applied and Environmental Microbiology, 69(6), 3069-3076. 10.1128/AEM.69.6.3069-3076.2003.
- Wilson, S.D., & Horne, D.W. (1982). Use of glycerol-cryoprotected Lactobacillus casei for microbiological assay of folic acid. Clinical Chemistry, 28(5), 1198-1200. https://doi.org/ 10.1093/clinchem/28.5.1198.
- Wright A.J.A, Dainty J.R., & Finglas P.M. (2007). Folic acid metabolism in human subjects revisited: potential implications for proposed mandatory folic acid fortification in the UK. The British Journal of Nutrition, 98(4), 667-75. 10.1017/ S0007114507777140.
- Yuksekdag Z.N., Zeydanlı, M. (2013). Folat eksikliği ve probiyotikler. Nevşehir Bilim ve Teknoloji Dergisi, 2(2), 21-36.
- Zahed, O., Khosravi-Darani, K., Mortazavian, A.M., & Mohammadi, A. (2022). Effects of cultivation conditions on biofortification of yogurt with natural folate by Propionibacterium freudenreichii. Biocatalysis and Agricultural Biotechnology, 39, 102267. https://doi.org/10.1016/ j.bcab.2021.102267.
- Zhang, J., Cai, D., Yang, M., Hao, Y., Zhu, Y., Chen, Z., Aziz, T., Sarwar, A., & Yang, Z. (2020). Screening of folate-producing lactic acid bacteria and modulatory effects of folate-biofortified yoghurt on gut dysbacteriosis of folate-deficient rats. Food Function, 11, 6308-6318. 10.1039/ d0fo00480d.
Production of Intra-/Extracellular Folate in Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus Bacteria Isolated from Traditional Turkish Yoghurts
Yıl 2024,
, 704 - 717, 30.06.2024
Meryem Nur Zeydanlı
,
Zehranur Yuksekdag
,
Berat Çınar Acar
Öz
This study, it was aimed to examined the bacteria that can be used as starter cultures in the generation of yoghurt with rich folate content. For this purpose, 31 Lactobacillus spp. and 32 Streptococcus spp. a total of 63 bacteria was isolated from yogurt made with traditional methods in various districts of Turkey. Biochemical identification of obtained bacteria was made with API 50 CH kit. Molecular identification of randomly selected 4 Lactobacillus and 4 Streptococus isolates with 16S rDNA gene regions were performed. Intracellular and extracellular folate production amounts of bacteria were designated in three different buffer applications (potassium phosphate, sodium phosphate and sodium acetate) in folate-free culture medium (FACM), skim milk and MRS/Elliker broth. It was statistically examined whether there was a significant difference between the media and buffer solutions used. In the application of potassium phosphate buffer in Skimmilk medium, Lactobacillus delbrueckii subsp. bulgaricus ZN1181 strain was found to have the highest intracellular folate production with a value of 105.6 µg/L, while Streptococcus thermophilus Z651 strain showed the highest extracellular folate production (79.9 µg/L) in FACM medium and potassium phosphate buffer.
Proje Numarası
05/2013-07
Kaynakça
- Agagunduz, D., Sahin, T.O., Ayten, S., Yılmaz, B., Günesliol, B.E., Russo, P., Spano, G., & Ozogul, F. (2022). Lactic acid bacteria as pre-technological, bioprotective and health-promoting cultures in the dairy food industry. Food Bioscience, 47, 101617. https://doi.org/10.1016/j.fbio.2022.101617.
- Albano, C., Silvetti, T., & Brasca, M. (2020). Screening of lactic acid bacteria producing folate and their potential use as adjunct cultures for cheese bio-enrichment. FEMS Microbiology Letters, 367, 9. https://doi.org/10.1093/femsle/ fnaa059.
- Aras, Z. (2011). Rapid diagnostic methods in microbiology. Turk Hijyen ve Deneysel Biyoloji Dergisi, 68(2), 97–104.
- Aswathy, R.G., Ismail, B., John, R.P., & Nampoothiri, K.M. (2008). Evaluation of the probiotic characteristics of newly isolated lactic acid bacteria. Applied Biochemistry and Biotechnology, 151, 244-255. 10.1007/s12010-008-8183-6.
- Albano, C., Silvetti, T., & Brasca, M. (2020). Screening of lactic acid bacteria producing folate and their potential use as adjunct cultures for cheese bio-enrichment. FEMS Microbiology Letters, 367. https://doi.org/10.1093/femsle/ fnaa059.
- Albuquerque, M.A.C., Yamacita, D.S., Bedani, R., LeBlanc, J.G., & Saad, S.M.I. (2019). Influence of passion fruit by-product and fructooligosaccharides on the viability of Streptococcus thermophilus TH-4 and Lactobacillus rhamnosus LGG in folate bio-enriched fermented soy products and their effect on probiotic survival and folate bio-accessibility under in vitro simulated gastrointestinal conditions. International Journal of Food Microbiology, 292, 126-136. https://doi.org/10.1016/ j.ijfoodmicro.2018.12.012.
- Baggott J.E., Oster R.A., & Tamura T. (2012). Meta-analysis of cancer risk in folic acid supplementation trials. Cancer Epidemiology, 36, 78-81. 10.1016/j.canep.2011.05.003.
- Bailey S.W., & Ayling J.E. (2009). The extremely slow and variable activity of dihydrofolate reductase in the human liver and its implications for high folic acid intake. Proceedings of the National Academy Sciences of the USA, 106(36), 15424-9. 10.1073/pnas.0902072106.
- Cucick, A.C.C., Gianni, K., Todorov, S.D., de LeBlanc, A.M., LeBlanc, J., & Franco, B.D.G.M. (2020). Evaluation of the bioavailability and intestinal effects of milk fermented by folate producing lactic acid bacteria in a depletion/repletion mice model. Journal of Functional Foods, 66, 103785.
https://doi.org/10.1016/j.jff.2020.103785.
- Da Silva, F.F.P., Biscola, V., LeBlanc, J.G., & de Melo Franco, B.D.G. (2016). Effect of indigenous lactic acid bacteria isolated from goat milk and cheeses on folate and riboflavin content of fermented goat milk. LWT-Food Science and Technology, 71, 155-161. ISSN: 0023-6438.
- dos Santos, H.R.M., Argolo, C.S., Argolo-Filho, R.C., & Loguercio, L.L.A. (2019). 16S rDNA PCR based theoretical to actual delta approach on culturable mock communities revealed severe losses of diversity information. BMC Microbiology, 19, 74. https://doi.org/10.1186/s12866-019-1446-2.
- Engevik, M.A., Morra, C.N., Röth, D., Engevik, K., Spinler, J.K., Devaraj, S., Crawford, S.E., Estes, M.K., Kalkum, M., & Versalovic, J. (2019). Microbial metabolic capacity for ıntestinal folate production and modulation of host folate receptors. Frontiers in Microbiology Microbial Physiology and Metabolism, 10. https://doi.org/10.3389/ fmicb.2019.02305.
- Fayemi, O.E., Akanni, G.B., Sobowale, S.S., Oelofse, A., & Buys, E.M. (2023). Potential for increasing folate contents of traditional African fermented sorghum gruel (Motoho) using presumptive probiotic lactic acid bacteria. Journal of Food Composition and Analysis, 115, 104850. https://doi.org/10.1016/j.jfca.2022.104850.
- Frey, J., & Nicolet, J. (1997). Molecular identification and epidemiology of animal mycoplasmas. Wiener Klinische Wochenschrift, 109 (14-15), 600-603.
- Greppi, A., Hemery, Y., Berrazaga, I. Almaksour, Z., & Humblot, C. (2017). The ability of lactobacilli isolated from traditional cereal-based fermented food to produce folate in culture media under different growth conditions. LWT-Food Science and Technology, 86, 277-84. 10.1016/j.lwt. 2017.08.007.
- Haghshenas, B., Abdullah, N., Nami, Y., Radiah, D., Rosli, R., & Khosroushahi, A.Y. (2014). Different effects of two newly-isolated probiotic Lactobacillus plantarum 15HN and Lactococcus lactis subsp. lactis 44 Lac strains from traditional dairy products on cancer cell lines. Anaerobe, 30, 51-59. 10.1016/j.anaerobe.2014.08.009.
- Hildebrand, L.A., Dumas, B., Milrod, C.J., & Hudspeth, J.C. (2021). Folate deficiency in an urban safety-net population. The American Journal of Medicine, 134(10), 1265-1269.
https://doi.org/10.1016/j.amjmed.2021.04.028.
- Iyer, R., & Tomar, S.K. (2009). Folate: A functional food constituent. Journal of Food Science, 74(9), R114-R122. 10.1111/j.1750-3841.2009.01359.x.
- Khalili, M., Rad, AH., Khosroushahi, A.Y., Khosravi, H., & Jafarzadeh, S. (2020). Application of probiotics in folate bio-fortification of yoghurt. Probiotics and Antimicrobial Proteins, 12, 756-763. https://doi.org/10.1007/s12602-019-09560-7.
- Kızılyıldırım, S., Köksal, F. (2023). Investigation of the antibiotic profiles and phlogenetic relationships of the lactobacillus species ısolated from goat’s and cow’s milk. KSU Journal of Agriculture and Nature. 26 (5), 1021-1026. https://doi.org/10.18016/ksutarimdoga.vi.1178550.
- Laiño, J.E., LeBlanc, J.G., De Giori, & G.S. (2012). Production of natural folates by lactic acid bacteria starter cultures isolated from artisanal Argentinean yogurts. Canadian Journal of Microbiology, 58, 581-588. https://doi.org/10.1139/ w2012-026.
- LeBlanc, J.G., de Giori, G.S., Smid, E.J., Hugenholtz, J., & Sesma, F. (2007). Folate production by lactic acid bacteria and other food-grade microorganisms. Communicating Current Research and Educational Topics and Trends in Applied Microbiology, 1, 329-339.
- LeBlanc, J.G., Laino, J.E., del Valle, M.J., Vannini, V., van Sinderen, D., Taranto, M.P., de Valdez, G.F., de Giori, G.S., Sesma, F. (2011). B-Group vitamin production by lactic acid bacteria - current knowledge and potential applications. Journal of Applied Microbiology, 111(6), 1297-1309. 10.1111/j.1365-2672.2011.05157.x.
- Levit, R., Savoy de Giori, G., de Moreno de LeBlanc, A., & LeBlanc, J.G. (2021). Recent update on lactic acid bacteria producing riboflavin and folates: Application for food fortification and treatment of intestinal inflammation. Journal of Applied Microbiology, 130, 1412-1424. ISSN 1364-5072.
- Liu, M., Chen, Q., Su, Y., Zeng, L., Wu, H., Gu, Q., Ping Li, P., Mahara, F.A., Nuraida, L., & Lioe, H.N. (2021). Folate in milk is fermented by lactic acid bacteria from different food sources. Preventive Nutrition and Food Science, 26(2), 230-240. https://doi.org/10. 3746/pnf.2021.26.2.230 Rydon 2016.
- Mahara, F.A., Nuraida, L., & Lioe, H.N. (2021). Folate in milk is fermented by lactic acid bacteria from different food sources. Preventive Nutrition and Food Science, 26(2), 230–240. https://doi.org/ 10.3746/pnf.2021.26.2.230Rydon 2016.
- Meucci, A., Rossetti, L., Zago, M., Monti, L. Giraffa, G., Carminati, D., & Tidona, F. (2018). Folates biosynthesis by Streptococcus thermophilus during growth in milk. Food Microbiology, 69, 116-122. 10.1016/j.fm.2017.08.001.
Patel, J.B. (2001). 16S rRNA gene sequencing for bacterial pathogen identification in the clinical laboratory. Molecular Diagnosis, 6(4), 313-21. 10.1054/modi.2001.29158.
- Pompei, A., Cordisco, L., Amaretti, A., Zanoni, S., Raimondi, S., Matteuzzi, D., & Rossi, M. (2007). Administration of folate-producing Bifidobacteria enhances folate status in Wistar rats. Journal of Nutrition, 137(12), 2742–2746. 10.1093/jn/ 137.12.2742.
- Rad, A.H., Khosroushahi, A.Y., Khalili, M., & Jafarzadeh, S. (2016). Folate bio-fortification of yoghurt and fermented milk: A review. Dairy Science and Technology, 96(4), 427-441. 10.1007/s13594-016-0286-1.
- Rossi, M., Amaretti, A., & Raimondi, S. (2011). Folate production by probiotic bacteria. Nutrients, 3, 118-134. 10.3390/nu3010118.
- Saubade, F., Hemery, Y.M., Guyot, J.P., & Humblot, C. (2017). Lactic acid fermentation is a tool for increasing the folate content of foods. Critical Reviews in Food Science and Nutrition, 57(18), 3894-3910. 10.1080/10408398.2016.1192986.
- Sybesma, W., Starrenburg, M., Tijsseling, L., Hoefnagel, M.H.N., & Hugenholtz, J. (2003a). Effect of cultivation conditions on folate production by lactic acid bacteria. Applied and Environmental Microbiology, 69(8), 4542-4548. 10.1128/AEM.69.8. 4542-4548.2003.
- Sybesma, W., Starrenburg, M., Kleerebezem, M., Mierau, I., de Vos W.M., & Hugenholtz, J. (2003b). Increased production of folate by metabolic engineering of Lactococcus lactis. Applied and Environmental Microbiology, 69(6), 3069-3076. 10.1128/AEM.69.6.3069-3076.2003.
- Wilson, S.D., & Horne, D.W. (1982). Use of glycerol-cryoprotected Lactobacillus casei for microbiological assay of folic acid. Clinical Chemistry, 28(5), 1198-1200. https://doi.org/ 10.1093/clinchem/28.5.1198.
- Wright A.J.A, Dainty J.R., & Finglas P.M. (2007). Folic acid metabolism in human subjects revisited: potential implications for proposed mandatory folic acid fortification in the UK. The British Journal of Nutrition, 98(4), 667-75. 10.1017/ S0007114507777140.
- Yuksekdag Z.N., Zeydanlı, M. (2013). Folat eksikliği ve probiyotikler. Nevşehir Bilim ve Teknoloji Dergisi, 2(2), 21-36.
- Zahed, O., Khosravi-Darani, K., Mortazavian, A.M., & Mohammadi, A. (2022). Effects of cultivation conditions on biofortification of yogurt with natural folate by Propionibacterium freudenreichii. Biocatalysis and Agricultural Biotechnology, 39, 102267. https://doi.org/10.1016/ j.bcab.2021.102267.
- Zhang, J., Cai, D., Yang, M., Hao, Y., Zhu, Y., Chen, Z., Aziz, T., Sarwar, A., & Yang, Z. (2020). Screening of folate-producing lactic acid bacteria and modulatory effects of folate-biofortified yoghurt on gut dysbacteriosis of folate-deficient rats. Food Function, 11, 6308-6318. 10.1039/ d0fo00480d.