Yeni Nesil Probiyotiklerin Üretim ve Uygulamalarında Karşılaşılan Zorluklar ve Çözüm Yolları
Özet
Yeni nesil sekanslama çalışmaları ve biyoinformatik alanındaki hızlı gelişmeler neticesinde insan bağırsak mikrobiyotası tüm detayları ile ortaya konmaya başlanmıştır. Bu çalışmalar bağırsak kökenli anaerobik kommensallerin sayıca azlığının çeşitli hastalıkların sebebi olabileceğini göstermiştir. Obezite, tip 2 diyabet, Alzheimer, demans, kanser gibi bazı hastalıkların teşhisinin konulduğu kişilerde bu bağırsak kökenli anaerob bakterilerin sağlıklı bireylere göre daha az olduğu görülmüştür. Buradan hareketle konvansiyonel probiyotiklere nazaran hastalıklarla ilişkisi net olarak ortaya konan ve ileride kişiselleştirilmiş tedavilerde kullanılması beklenen bu bakterilerin izole edilmesi, tanımlanması, karakteristiklerinin ortaya konması gerekliliği oluşmuştur. Yeni nesil probiyotikler olarak isimlendirilen bu bağırsak kökenli kommensallerin büyük çoğunluğunun oksijene çok hassas olması bu bakterilerin tıp alanında ilaç ve katkı olarak kullanımının ve gıda sanayiinde formülasyonlara girmesinin önünde en büyük engeldir. Bu çalışmada yeni nesil probiyotiklerin teknolojik olarak rahat kullanımını sağlayacak en son gelişmeler ve yaklaşımlar özetlenmiş ve ilerleyen yıllarda hayatımızın çok önemli bir parçası olması öngörülen bu bakteriler hakkında bir perspektif çizilmiştir.
As a result of new generation sequencing studies and rapid developments in the field of bioinformatics, the human intestinal microbiota has begun to be revealed in full detail. These studies have shown that the low number of intestinal anaerobic commensals may be the cause
of various diseases. It has been observed that these intestinal anaerobic bacteria are less in people diagnosed with certain diseases such as obesity, type 2 diabetes, Alzheimer's, dementia and cancer compared to healthy individuals. Based on this, it has become necessary to isolate, identify and reveal the characteristics of these bacteria which have a clear relationship with diseases compared to conventional ones and are expected to be used in personalized treatments in the future. The fact that the majority of these gut-origin commensals, called next generation probiotics, are very sensitive to oxygen is the biggest obstacle to the use of these bacteria as drugs and additives in the medical field and their introduction into formulations in the food industry. In this study, the latest developments and approaches that will enable the technologically convenient use of next generation probiotics are summarized and a perspective is drawn about these bacteria, which are expected to be a very important part of our lives in the coming years.
Referanslar
Allen, S. J., Martinez, E. G., Gregorio, G. V. & Dans, L. F. (2010) Probiotics for treating acute infectious diarrhoea. Cochrane Database of Systematic Reviews. (11).
Allouche, R., Dupont, S., Charriau, A., Gervais, P., Beney, L. & Chambin, O. (2018) Optimized tableting for extremely oxygen-sensitive probiotics using direct compression. International Journal of Pharmaceutics. 538 (1-2), 14-20.
Almeida, D., Machado, D., Andrade, J. C., Mendo, S., Gomes, A. M. & Freitas, A. C. (2020) Evolving trends in next-generation probiotics: a 5W1H perspective. Critical reviews in food science and nutrition. 60 (11), 1783-1796.
Barbosa, J. C., Machado, D., Almeida, D., Andrade, J. C., Brandelli, A., Gomes, A. M. & Freitas, A. C. (2022) Next-generation probiotics. In Probiotics (pp. 483-502). Elsevier.
Bellali, S., Khalil, J. B., Fontanini, A., Raoult, D. & Lagier, J.-C. (2020) A new protectant medium preserving bacterial viability after freeze drying. Microbiological research. 236, 126454.
Bircher, L., Geirnaert, A., Hammes, F., Lacroix, C. & Schwab, C. (2018) Effect of cryopreservation and lyophilization on viability and growth of strict anaerobic human gut microbes. Microbial biotechnology. 11 (4), 721-733.
Blaabjerg, S., Artzi, D. M. & Aabenhus, R. (2017) Probiotics for the prevention of antibiotic-associated diarrhea in outpatients—a systematic review and meta-analysis. Antibiotics. 6 (4), 21.
Boesmans, L., Valles-Colomer, M., Wang, J., Eeckhaut, V., Falony, G., Ducatelle, R., Van Immerseel, F., Raes, J. & Verbeke, K. (2018) Butyrate producers as potential next-generation probiotics: safety assessment of the administration of Butyricicoccus pullicaecorum to healthy volunteers. Msystems. 3 (6), 10.1128/msystems. 00094-00018.
Brodmann, T., Endo, A., Gueimonde, M., Vinderola, G., Kneifel, W., de Vos, W. M., Salminen, S. & Gómez-Gallego, C. (2017) Safety of novel microbes for human consumption: practical examples of assessment in the European Union. Frontiers in microbiology. 8, 1725.
Chang, Y., Yang, Y., Xu, N., Mu, H., Zhang, H. & Duan, J. (2020) Improved viability of Akkermansia muciniphila by encapsulation in spray dried succinate-grafted alginate doped with epigallocatechin-3-gallate. International Journal of Biological Macromolecules. 159, 373-382.
Cho, Y. A. & Kim, J. (2015) Effect of probiotics on blood lipid concentrations: a meta-analysis of randomized controlled trials. Medicine. 94 (43).
Crovesy, L., Gongalves, D. & Trigo, E. L. (2017) Probiotics in allergy treatment: a literature review. Revista Española de Nutrición Humana y Dietética. 21 (3), 293-299.
Cunningham, M., Azcarate-Peril, M. A.,Barnard, A., van Sinderen, D., Vulevic, J., & Gibson, G. R. (2021) Shaping the future of probiotics and prebiotics. Trends in Microbiology.
De Filippis, F., Esposito, A. & Ercolini, D. (2022) Outlook on next-generation probiotics from the human gut. Cellular and Molecular Life Sciences. 79 (2), 76.
De Filippis, F., Paparo, L., Nocerino, R., Della Gatta, G., Carucci, L., Russo, R., Pasolli, E., Ercolini, D. & Berni Canani, R. (2021) Specific gut microbiome signatures and the associated pro-inflamatory functions are linked to pediatric allergy and acquisition of immune tolerance. Nature communications. 12 (1), 5958.
De Vos, W. M. & Seegers, J. F. M. L. (2020) Methods for culturing and preserving Eubacterium hallii and treating disease and preparation thereof. In: Google Patents.
Demirci, T. (2023) Yeni Nesil Probiyotikler: Taksonomileri, Güvenlikleri, Uygulamaları ve Potansiyel Sağlık Faydaları. In A. Oraç (Ed.), Gıdanın Geleceği (Vol. 1, pp. 295-323). Nobel Akademik Yayıncılık.
Deng, H., Li. Z., Tan, Y., Guo, Z., Liu, Y., Wang, Y., Yuan, Y., Yang, R., Bi, Y., Bai, Y. & Zhi, F. (2016) A novel strain of Bacteroides fragilis enhances phagocytosis and polarises M1 macrophages. Scientific reports. 6 (1), 29401.
Doron, S. & Snydman, D. R. (2015) Risk and safety of probiotics. Clinical Infectious Diseases, 60 (suppl_2), S129-S134.
Duncan, S. H., Hold, G. L., Harmsen, H. J., Stewart, C. S. & Flint, H. J. (2002) Growth requirements and fermentation products of Fusobacterium prausnitzii, and a proposal to reclassify it as Faecalibacterium prausnitzii gen. nov., comb. nov. International journal of systematic and evolutionary microbiology. 52 (6), 2141-2146.
Eeckhaut, V., Ducatelle, R., Sas, B., Vermeire, S. & Van Immerseel, F. (2014) Progress towards butyrate-producing pharmabiotics: Butyricicoccus pullicaecorum capsule and efficacy in TNBS models in comparison with therapeutics. Gut. 63 (2), 367-367.
Everard, A., Matamoros, S., Geurts, L., Delzenne, N. M. & Cani, P. D. (2014) Saccharomyces boulardii administration changes gut microbiota and reduces hepatic steatosis, low-grade inflammation, and fat mass in obese and type 2 diabetic db/db mice. MBio. 5 (3), e01011-01014.
Ford, A. C., Quigley, E. M., Lacy, B. E., Lembo, A. J., Saito, Y. A., Schiller, L. R., Soffer, E. E., Spiegel, B. M. & Moayyedi, P. (2014) Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Official journal of the American College of Gastroenterology| ACG. 109 (10), 1547-1561.
Hill, C., Guarner, F., Reid, G., Gibson, G. R., Merenstein, D. J., Pot, B., Morelli, L., Berni Canini, R., Flint, H. J., Salminen, S., Calder, P. C. & Sanders, M. E. (2014) The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature reviews Gastroenterology ve hepatology. 11 (8), 506-514.
Kadooka, Y., Sato, M., Ogawa, A., Miyoshi, M., Uenishi, H., Ogawa, H., Ikuyama, K., Kagoshima, M. & Tsuchida, T. (2013) Effect of Lactobacillus gasseri SBT2055 in fermented milk on abdominal adiposity in adults in a randomised controlled trial. British Journal of Nutrition. 110 (9), 1696-1703.
Khan, M. T., Browne, W. R., van Dijl, J. M. & Harmsen, H. J. (2012) How can Faecalibacterium prausnitzii employ riboflavin for extracellular electron transfer? In: Mary Ann Liebert. Inc. 140 Huguenot Street, 3rd Floor New Rochelle, NY 10801 USA.
Khan, M. T., Dwibedi, C., Sundh, D., Pradhan, M., Kraft, J. D., Caesar, R., Tremaroli, V., Lorentzon, M. & Bäckhed, F. (2023) Synergy and oxygen adaptation for development of next-generation probiotics. Nature. 620 (7973), 381-385.
Khan, M. T, van Dijl, J. M. & Harmsen, H. J. (2014) Antioxidants keep the potentially probiotic but highly oxygen-sensitive human gut bacterium Faecalibacterium prausnitzii alive at ambient air. PloS one. 9 (5), e96097.
Kothari, D., Patel, S. & Kim, S.-K. (2019) Probiotic supplements might not be universally-effective and safe: A review. Biomedicine ve Pharmacotherapy. 111, 537-547.
Koutnikova, H., Genser, B., Monteiro-Sepulveda, M., Faurie, J.-M., Rizkalla, S., Schrezenmeir, J. & Clément, K. (2019) Impact of bacterial probiotics on obesity, diabetes and non-alcoholic fatty liver disease related variables: a systematic review and meta-analysis of randomised controlled trials. BMJ open. 9 (3), e017995.
Kumari, M. & Kokkiligadda, A. (2021) Next-Generation Probiotics. In Advances in Probiotics. (pp. 45-79). Elsevier.
Li, L., Han, Z., Niu, X., Zhang, G., Jia, Y., Zhang, S. & He, C. (2019) Probiotic supplementation for prevention of atopic dermatitis in infants and children: a systematic review and meta-analysis. American journal of clinical dermatology. 20, 367-377.
Li, Z. Deng, H., Zhou, Y., Tan, Y., Wang, X., Han, Y., Liu, Y., Wang, Y., Yang, R., Bi, Y. & F, Zhi. (2017) Bioluminescence imaging to track Bacteroides fragilis inhibition of Vibrio parahaemolyticus infection in mice. Frontiers in Cellular and Infection Microbiology. 7, 170.
Li, Z., Hu, G., Zhu, L., Sun, Z., Jiang, Y., Gao, M.-j. & Zhan, X. (2021) Study of growth, metabolism, and morphology of Akkermansia muciniphila with an in vitro advanced bionic intestinal reactor. BMC microbiology. 21, 1-12.
Lilly, D. M. & Stillwell, R. H. (1965) Probiotics: growth-promoting factors produced by microorganisms. Science. 147 (3659), 747-748.
Liu, R., Hong, J., Xu, X., Feng, Q., Zhang, D., Gu, Y., Shi, J., Zhao, S., Liu, W., Wang, X., Xia, H., Liu, Z., Cui, B., Liang, P ve ark. (2017) Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention. Nature medicine. 23 (7), 859-868.
Machado, D., Barbosa, J. C., Almeida, D., Andrade, J. C., Freitas, A. C. & Gomes, A. M. (2022) Insights into the antimicrobial resistance profile of a next generation probiotic Akkermansia muciniphila DSM 22959. International Journal of Environmental Research and Public Health. 19 (15), 9152.
Marcial-Coba, M. S., Cieplak, T., Cahú, T. B., Blennow, A., Knøchel, S. & Nielsen, D. S. (2018) Viability of microencapsulated Akkermansia muciniphila and Lactobacillus plantarum during freeze-drying, storage and in vitro simulated upper gastrointestinal tract passage. Food ve function. 9 (11), 5868-5879.
Marcial-Coba, M. S., Saaby, L., Knøchel, S. & Nielsen, D. S. (2019) Dark chocolate as a stable carrier of microencapsulated Akkermansia muciniphila and Lactobacillus casei. FEMS Microbiology Letters. 366 (2), fny290.
Meslier, V., Laiola, M., Roager, H, M,. De Filippis, F., Roume, H., Quinquis, B., Giacco, R., Mennella, I. ve ark. (2020) Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake. Gut. 69 (7), 1258-1268.
O’Toole, P. W., Marchesi, J. R. & Hill, C. (2017) Next-generation probiotics: the spectrum from probiotics to live biotherapeutics. Nature microbiology. 2 (5), 1-6.
Ouwerkerk, J., Aalvink, S., Belzer, C. & De Vos, W. (2017) Preparation and preservation of viable Akkermansia muciniphila cells for therapeutic interventions. Beneficial microbes. 8 (2), 163-169.
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. (2019) Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Frontiers in immunology. 277.
Pawar, R., Dhawal, P., Nabar, B., Barve, S. & Zambare, V. (2022) Mechanisms and applications of probiotics in healthcare industry. In Biotechnology in Healthcare. (pp. 225-257). Elsevier.
Perraudeau, F., Mc Murdie, P., Bullard J., Cheng, A., Cutcliffe C., Deo, A., Eid, J., Gines, J., Iyer, M. ve ark. (2020) Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ Open Diabetes Research and Care. 8 (1), e001319.
Quin, C., Estaki, M., Vollman, D., Barnett, J. Gill, S. & Gibson, D. (2018) Probiotic supplementation and associated infant gut microbiome and health: a cautionary retrospective clinical comparison. Scientific reports. 8 (1), 8283.
Raise, A., Dupont, S., Iaconelli, C., Caliri, C., Charriau, A., Gervais, P., Chambin, O. & Beney, L. (2020) Comparison of two encapsulation processes to protect the commensal gut probiotic bacterium Faecalibacterium prausnitzii from the digestive tract. Journal of Drug Delivery Science and Technology. 56, 101608.
Rossi, O., van Berkel, L., Chain, F., Khan, M. T., Taverne, N., Sokol. H., Duncan, S., ve ark. (2016) Faecalibacterium prausnitzii A2-165 has a high capacity to induce IL-10 in human and murine dendritic cells and modulates T cell responses. Scientific reports. 6 (1), 18507.
Routy, B., Gopalakrishnan, V., Daillère, R., Zitvogel, L., Wargo, J. A. & Kroemer, G. (2018) The gut microbiota influences anticancer immunosurveillance and general health. Nature Reviews Clinical Oncology. 15 (6), 382-396.
Sanders, M. E., Akkermans, L. M., Haller, D., Hammerman, C., Heimbach, J. T., Hörmannsperger, G. & Huys, G. (2010). Safety assessment of probiotics for human use. Gut Microbes. 1 (3), 164-185.
Shin, J.-H., Nam, M. H., Lee, H., Lee, J.-S., Kim, H., Chung, M.-J. & Seo, J.-G. (2018) Amelioration of obesity-related characteristics by a probiotic formulation in a high-fat diet-induced obese rat model. European journal of nutrition. 57, 2081-2090.
Singh, T. P. & Natraj, B. H. (2021) Next-generation probiotics: a promising approach towards designing personalized medicine. Critical Reviews in Microbiology. 47 (4), 479-498.
Staudacher, H. M. & Whelan, K. (2016) Altered gastrointestinal microbiota in irritable bowel syndrome and its modification by diet: probiotics, prebiotics and the low FODMAP diet. Proceedings of the Nutrition Society. 75 (3), 306-318.
Su, G. L., Ko, C. W., Bercik, P., Falck-Ytter, Y., Sultan, S., Weizman, A. V. & Morgan, R. L. (2020) AGA clinical practice guidelines on the role of probiotics in the management of gastrointestinal disorders. Gastroenterology. 159 (2), 697-705.
Suez, J., Zmora, N. & Elinav, E. (2020) Probiotics in the next-generation sequencing era. Gut Microbes. 11 (1), 77-93.
Suez, J., Zmora, N., Segal, E. & Elinav, E. (2019) The pros, cons, and many unknowns of probiotics. Nature medicine. 25 (5), 716-729.
Torp, A. M., Bahl, M. I., Boisen, A. & Licht, T. R. (2022) Optimizing oral delivery of next generation probiotics. Trends in Food Science ve Technology. 119, 101-109.
van der Ark, K. C., Aalvink, S., Suarez‐Diez, M., Schaap, P. J., de Vos, W. M. & Belzer, C. (2018) Model‐driven design of a minimal medium for Akkermansia muciniphila confirms mucus adaptation. Microbial biotechnology. 11 (3), 476-485.
van der Ark, K. C., Nugroho, A. D. W., Berton-Carabin, C., Wang, C., Belzer, C., de Vos, W. M. & Schroen, K. (2017) Encapsulation of the therapeutic microbe Akkermansia muciniphila in a double emulsion enhances survival in simulated gastric conditions. Food Research International. 102, 372-379.
Vass, P., Pantea, E., Domokos, A., Hirsch, E., Domjan, J., Nemeth, A., Molnar, M., & Feher, C. (2020) Electrospun solid formulation of anaerobic gut microbiome bacteria. AAPS PharmTech. 21, 1-9.
Vedor, R., Machado, D., Barbosa, J. C., Almeida, D. & Gomes, A. M. (2023) Incorporation of Bifidobacterium animalis subspecies lactis BB-12® and Akkermansia muciniphila in chocolate matrices. LWT. 187, 115361.
Yoon, H. S., Cho C. H., Yun, M. S., Jang, S. J., You, H. J. ve ark. (2021) Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nature microbiology. 6 (5), 563-573.
Zhang, H., Duan, Y., Cai, F., Cao, D., Wang, L., Qiao, Z., Hong, Q., Li, N., Zheng, Y., Su, M., Liu, Z. & Zhu B. (2022) Next-Generation Probiotics: Microflora Intervention to Human Diseases. BioMed Research International. 2022.
Zhuang, X., Xiong, L., Li, L., Li, M. & Chen, M. (2017) Alterations of gut microbiota in patients with irritable bowel syndrome: A systematic review and meta‐analysis. Journal of gastroenterology and hepatology. 32 (1), 28-38.
Zmora, N., Suez, J. & Elinav, E. (2019) You are what you eat: diet, health and the gut microbiota. Nature reviews Gastroenterology ve hepatology. 16 (1), 35-56.
Zmora, N., Zilberman-Schapira, G., Suez, J., Mor, U., Dori-Bachash, M., Bashiardes, S ve ark. (2018) Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell. 174 (6), 1388-1405. e1321.
Referanslar
Allen, S. J., Martinez, E. G., Gregorio, G. V. & Dans, L. F. (2010) Probiotics for treating acute infectious diarrhoea. Cochrane Database of Systematic Reviews. (11).
Allouche, R., Dupont, S., Charriau, A., Gervais, P., Beney, L. & Chambin, O. (2018) Optimized tableting for extremely oxygen-sensitive probiotics using direct compression. International Journal of Pharmaceutics. 538 (1-2), 14-20.
Almeida, D., Machado, D., Andrade, J. C., Mendo, S., Gomes, A. M. & Freitas, A. C. (2020) Evolving trends in next-generation probiotics: a 5W1H perspective. Critical reviews in food science and nutrition. 60 (11), 1783-1796.
Barbosa, J. C., Machado, D., Almeida, D., Andrade, J. C., Brandelli, A., Gomes, A. M. & Freitas, A. C. (2022) Next-generation probiotics. In Probiotics (pp. 483-502). Elsevier.
Bellali, S., Khalil, J. B., Fontanini, A., Raoult, D. & Lagier, J.-C. (2020) A new protectant medium preserving bacterial viability after freeze drying. Microbiological research. 236, 126454.
Bircher, L., Geirnaert, A., Hammes, F., Lacroix, C. & Schwab, C. (2018) Effect of cryopreservation and lyophilization on viability and growth of strict anaerobic human gut microbes. Microbial biotechnology. 11 (4), 721-733.
Blaabjerg, S., Artzi, D. M. & Aabenhus, R. (2017) Probiotics for the prevention of antibiotic-associated diarrhea in outpatients—a systematic review and meta-analysis. Antibiotics. 6 (4), 21.
Boesmans, L., Valles-Colomer, M., Wang, J., Eeckhaut, V., Falony, G., Ducatelle, R., Van Immerseel, F., Raes, J. & Verbeke, K. (2018) Butyrate producers as potential next-generation probiotics: safety assessment of the administration of Butyricicoccus pullicaecorum to healthy volunteers. Msystems. 3 (6), 10.1128/msystems. 00094-00018.
Brodmann, T., Endo, A., Gueimonde, M., Vinderola, G., Kneifel, W., de Vos, W. M., Salminen, S. & Gómez-Gallego, C. (2017) Safety of novel microbes for human consumption: practical examples of assessment in the European Union. Frontiers in microbiology. 8, 1725.
Chang, Y., Yang, Y., Xu, N., Mu, H., Zhang, H. & Duan, J. (2020) Improved viability of Akkermansia muciniphila by encapsulation in spray dried succinate-grafted alginate doped with epigallocatechin-3-gallate. International Journal of Biological Macromolecules. 159, 373-382.
Cho, Y. A. & Kim, J. (2015) Effect of probiotics on blood lipid concentrations: a meta-analysis of randomized controlled trials. Medicine. 94 (43).
Crovesy, L., Gongalves, D. & Trigo, E. L. (2017) Probiotics in allergy treatment: a literature review. Revista Española de Nutrición Humana y Dietética. 21 (3), 293-299.
Cunningham, M., Azcarate-Peril, M. A.,Barnard, A., van Sinderen, D., Vulevic, J., & Gibson, G. R. (2021) Shaping the future of probiotics and prebiotics. Trends in Microbiology.
De Filippis, F., Esposito, A. & Ercolini, D. (2022) Outlook on next-generation probiotics from the human gut. Cellular and Molecular Life Sciences. 79 (2), 76.
De Filippis, F., Paparo, L., Nocerino, R., Della Gatta, G., Carucci, L., Russo, R., Pasolli, E., Ercolini, D. & Berni Canani, R. (2021) Specific gut microbiome signatures and the associated pro-inflamatory functions are linked to pediatric allergy and acquisition of immune tolerance. Nature communications. 12 (1), 5958.
De Vos, W. M. & Seegers, J. F. M. L. (2020) Methods for culturing and preserving Eubacterium hallii and treating disease and preparation thereof. In: Google Patents.
Demirci, T. (2023) Yeni Nesil Probiyotikler: Taksonomileri, Güvenlikleri, Uygulamaları ve Potansiyel Sağlık Faydaları. In A. Oraç (Ed.), Gıdanın Geleceği (Vol. 1, pp. 295-323). Nobel Akademik Yayıncılık.
Deng, H., Li. Z., Tan, Y., Guo, Z., Liu, Y., Wang, Y., Yuan, Y., Yang, R., Bi, Y., Bai, Y. & Zhi, F. (2016) A novel strain of Bacteroides fragilis enhances phagocytosis and polarises M1 macrophages. Scientific reports. 6 (1), 29401.
Doron, S. & Snydman, D. R. (2015) Risk and safety of probiotics. Clinical Infectious Diseases, 60 (suppl_2), S129-S134.
Duncan, S. H., Hold, G. L., Harmsen, H. J., Stewart, C. S. & Flint, H. J. (2002) Growth requirements and fermentation products of Fusobacterium prausnitzii, and a proposal to reclassify it as Faecalibacterium prausnitzii gen. nov., comb. nov. International journal of systematic and evolutionary microbiology. 52 (6), 2141-2146.
Eeckhaut, V., Ducatelle, R., Sas, B., Vermeire, S. & Van Immerseel, F. (2014) Progress towards butyrate-producing pharmabiotics: Butyricicoccus pullicaecorum capsule and efficacy in TNBS models in comparison with therapeutics. Gut. 63 (2), 367-367.
Everard, A., Matamoros, S., Geurts, L., Delzenne, N. M. & Cani, P. D. (2014) Saccharomyces boulardii administration changes gut microbiota and reduces hepatic steatosis, low-grade inflammation, and fat mass in obese and type 2 diabetic db/db mice. MBio. 5 (3), e01011-01014.
Ford, A. C., Quigley, E. M., Lacy, B. E., Lembo, A. J., Saito, Y. A., Schiller, L. R., Soffer, E. E., Spiegel, B. M. & Moayyedi, P. (2014) Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Official journal of the American College of Gastroenterology| ACG. 109 (10), 1547-1561.
Hill, C., Guarner, F., Reid, G., Gibson, G. R., Merenstein, D. J., Pot, B., Morelli, L., Berni Canini, R., Flint, H. J., Salminen, S., Calder, P. C. & Sanders, M. E. (2014) The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature reviews Gastroenterology ve hepatology. 11 (8), 506-514.
Kadooka, Y., Sato, M., Ogawa, A., Miyoshi, M., Uenishi, H., Ogawa, H., Ikuyama, K., Kagoshima, M. & Tsuchida, T. (2013) Effect of Lactobacillus gasseri SBT2055 in fermented milk on abdominal adiposity in adults in a randomised controlled trial. British Journal of Nutrition. 110 (9), 1696-1703.
Khan, M. T., Browne, W. R., van Dijl, J. M. & Harmsen, H. J. (2012) How can Faecalibacterium prausnitzii employ riboflavin for extracellular electron transfer? In: Mary Ann Liebert. Inc. 140 Huguenot Street, 3rd Floor New Rochelle, NY 10801 USA.
Khan, M. T., Dwibedi, C., Sundh, D., Pradhan, M., Kraft, J. D., Caesar, R., Tremaroli, V., Lorentzon, M. & Bäckhed, F. (2023) Synergy and oxygen adaptation for development of next-generation probiotics. Nature. 620 (7973), 381-385.
Khan, M. T, van Dijl, J. M. & Harmsen, H. J. (2014) Antioxidants keep the potentially probiotic but highly oxygen-sensitive human gut bacterium Faecalibacterium prausnitzii alive at ambient air. PloS one. 9 (5), e96097.
Kothari, D., Patel, S. & Kim, S.-K. (2019) Probiotic supplements might not be universally-effective and safe: A review. Biomedicine ve Pharmacotherapy. 111, 537-547.
Koutnikova, H., Genser, B., Monteiro-Sepulveda, M., Faurie, J.-M., Rizkalla, S., Schrezenmeir, J. & Clément, K. (2019) Impact of bacterial probiotics on obesity, diabetes and non-alcoholic fatty liver disease related variables: a systematic review and meta-analysis of randomised controlled trials. BMJ open. 9 (3), e017995.
Kumari, M. & Kokkiligadda, A. (2021) Next-Generation Probiotics. In Advances in Probiotics. (pp. 45-79). Elsevier.
Li, L., Han, Z., Niu, X., Zhang, G., Jia, Y., Zhang, S. & He, C. (2019) Probiotic supplementation for prevention of atopic dermatitis in infants and children: a systematic review and meta-analysis. American journal of clinical dermatology. 20, 367-377.
Li, Z. Deng, H., Zhou, Y., Tan, Y., Wang, X., Han, Y., Liu, Y., Wang, Y., Yang, R., Bi, Y. & F, Zhi. (2017) Bioluminescence imaging to track Bacteroides fragilis inhibition of Vibrio parahaemolyticus infection in mice. Frontiers in Cellular and Infection Microbiology. 7, 170.
Li, Z., Hu, G., Zhu, L., Sun, Z., Jiang, Y., Gao, M.-j. & Zhan, X. (2021) Study of growth, metabolism, and morphology of Akkermansia muciniphila with an in vitro advanced bionic intestinal reactor. BMC microbiology. 21, 1-12.
Lilly, D. M. & Stillwell, R. H. (1965) Probiotics: growth-promoting factors produced by microorganisms. Science. 147 (3659), 747-748.
Liu, R., Hong, J., Xu, X., Feng, Q., Zhang, D., Gu, Y., Shi, J., Zhao, S., Liu, W., Wang, X., Xia, H., Liu, Z., Cui, B., Liang, P ve ark. (2017) Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention. Nature medicine. 23 (7), 859-868.
Machado, D., Barbosa, J. C., Almeida, D., Andrade, J. C., Freitas, A. C. & Gomes, A. M. (2022) Insights into the antimicrobial resistance profile of a next generation probiotic Akkermansia muciniphila DSM 22959. International Journal of Environmental Research and Public Health. 19 (15), 9152.
Marcial-Coba, M. S., Cieplak, T., Cahú, T. B., Blennow, A., Knøchel, S. & Nielsen, D. S. (2018) Viability of microencapsulated Akkermansia muciniphila and Lactobacillus plantarum during freeze-drying, storage and in vitro simulated upper gastrointestinal tract passage. Food ve function. 9 (11), 5868-5879.
Marcial-Coba, M. S., Saaby, L., Knøchel, S. & Nielsen, D. S. (2019) Dark chocolate as a stable carrier of microencapsulated Akkermansia muciniphila and Lactobacillus casei. FEMS Microbiology Letters. 366 (2), fny290.
Meslier, V., Laiola, M., Roager, H, M,. De Filippis, F., Roume, H., Quinquis, B., Giacco, R., Mennella, I. ve ark. (2020) Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake. Gut. 69 (7), 1258-1268.
O’Toole, P. W., Marchesi, J. R. & Hill, C. (2017) Next-generation probiotics: the spectrum from probiotics to live biotherapeutics. Nature microbiology. 2 (5), 1-6.
Ouwerkerk, J., Aalvink, S., Belzer, C. & De Vos, W. (2017) Preparation and preservation of viable Akkermansia muciniphila cells for therapeutic interventions. Beneficial microbes. 8 (2), 163-169.
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. (2019) Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Frontiers in immunology. 277.
Pawar, R., Dhawal, P., Nabar, B., Barve, S. & Zambare, V. (2022) Mechanisms and applications of probiotics in healthcare industry. In Biotechnology in Healthcare. (pp. 225-257). Elsevier.
Perraudeau, F., Mc Murdie, P., Bullard J., Cheng, A., Cutcliffe C., Deo, A., Eid, J., Gines, J., Iyer, M. ve ark. (2020) Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ Open Diabetes Research and Care. 8 (1), e001319.
Quin, C., Estaki, M., Vollman, D., Barnett, J. Gill, S. & Gibson, D. (2018) Probiotic supplementation and associated infant gut microbiome and health: a cautionary retrospective clinical comparison. Scientific reports. 8 (1), 8283.
Raise, A., Dupont, S., Iaconelli, C., Caliri, C., Charriau, A., Gervais, P., Chambin, O. & Beney, L. (2020) Comparison of two encapsulation processes to protect the commensal gut probiotic bacterium Faecalibacterium prausnitzii from the digestive tract. Journal of Drug Delivery Science and Technology. 56, 101608.
Rossi, O., van Berkel, L., Chain, F., Khan, M. T., Taverne, N., Sokol. H., Duncan, S., ve ark. (2016) Faecalibacterium prausnitzii A2-165 has a high capacity to induce IL-10 in human and murine dendritic cells and modulates T cell responses. Scientific reports. 6 (1), 18507.
Routy, B., Gopalakrishnan, V., Daillère, R., Zitvogel, L., Wargo, J. A. & Kroemer, G. (2018) The gut microbiota influences anticancer immunosurveillance and general health. Nature Reviews Clinical Oncology. 15 (6), 382-396.
Sanders, M. E., Akkermans, L. M., Haller, D., Hammerman, C., Heimbach, J. T., Hörmannsperger, G. & Huys, G. (2010). Safety assessment of probiotics for human use. Gut Microbes. 1 (3), 164-185.
Shin, J.-H., Nam, M. H., Lee, H., Lee, J.-S., Kim, H., Chung, M.-J. & Seo, J.-G. (2018) Amelioration of obesity-related characteristics by a probiotic formulation in a high-fat diet-induced obese rat model. European journal of nutrition. 57, 2081-2090.
Singh, T. P. & Natraj, B. H. (2021) Next-generation probiotics: a promising approach towards designing personalized medicine. Critical Reviews in Microbiology. 47 (4), 479-498.
Staudacher, H. M. & Whelan, K. (2016) Altered gastrointestinal microbiota in irritable bowel syndrome and its modification by diet: probiotics, prebiotics and the low FODMAP diet. Proceedings of the Nutrition Society. 75 (3), 306-318.
Su, G. L., Ko, C. W., Bercik, P., Falck-Ytter, Y., Sultan, S., Weizman, A. V. & Morgan, R. L. (2020) AGA clinical practice guidelines on the role of probiotics in the management of gastrointestinal disorders. Gastroenterology. 159 (2), 697-705.
Suez, J., Zmora, N. & Elinav, E. (2020) Probiotics in the next-generation sequencing era. Gut Microbes. 11 (1), 77-93.
Suez, J., Zmora, N., Segal, E. & Elinav, E. (2019) The pros, cons, and many unknowns of probiotics. Nature medicine. 25 (5), 716-729.
Torp, A. M., Bahl, M. I., Boisen, A. & Licht, T. R. (2022) Optimizing oral delivery of next generation probiotics. Trends in Food Science ve Technology. 119, 101-109.
van der Ark, K. C., Aalvink, S., Suarez‐Diez, M., Schaap, P. J., de Vos, W. M. & Belzer, C. (2018) Model‐driven design of a minimal medium for Akkermansia muciniphila confirms mucus adaptation. Microbial biotechnology. 11 (3), 476-485.
van der Ark, K. C., Nugroho, A. D. W., Berton-Carabin, C., Wang, C., Belzer, C., de Vos, W. M. & Schroen, K. (2017) Encapsulation of the therapeutic microbe Akkermansia muciniphila in a double emulsion enhances survival in simulated gastric conditions. Food Research International. 102, 372-379.
Vass, P., Pantea, E., Domokos, A., Hirsch, E., Domjan, J., Nemeth, A., Molnar, M., & Feher, C. (2020) Electrospun solid formulation of anaerobic gut microbiome bacteria. AAPS PharmTech. 21, 1-9.
Vedor, R., Machado, D., Barbosa, J. C., Almeida, D. & Gomes, A. M. (2023) Incorporation of Bifidobacterium animalis subspecies lactis BB-12® and Akkermansia muciniphila in chocolate matrices. LWT. 187, 115361.
Yoon, H. S., Cho C. H., Yun, M. S., Jang, S. J., You, H. J. ve ark. (2021) Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nature microbiology. 6 (5), 563-573.
Zhang, H., Duan, Y., Cai, F., Cao, D., Wang, L., Qiao, Z., Hong, Q., Li, N., Zheng, Y., Su, M., Liu, Z. & Zhu B. (2022) Next-Generation Probiotics: Microflora Intervention to Human Diseases. BioMed Research International. 2022.
Zhuang, X., Xiong, L., Li, L., Li, M. & Chen, M. (2017) Alterations of gut microbiota in patients with irritable bowel syndrome: A systematic review and meta‐analysis. Journal of gastroenterology and hepatology. 32 (1), 28-38.
Zmora, N., Suez, J. & Elinav, E. (2019) You are what you eat: diet, health and the gut microbiota. Nature reviews Gastroenterology ve hepatology. 16 (1), 35-56.
Zmora, N., Zilberman-Schapira, G., Suez, J., Mor, U., Dori-Bachash, M., Bashiardes, S ve ark. (2018) Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell. 174 (6), 1388-1405. e1321.