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D’Aimmo et al. Microbiome Res Rep 2024;3:11                   Microbiome Research
               DOI: 10.20517/mrr.2023.59
                                                                                               Reports




               Review                                                                        Open Access



               Folate-producing bifidobacteria: metabolism,
               genetics, and relevance


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               Maria Rosaria D’Aimmo , Maria Satti , Donatella Scarafile , Monica Modesto , Stefano Pascarelli , Simone
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               Andrea Biagini , Donata Luiselli , Paola Mattarelli 2          , Thomas Andlid 6
               1
                BioGaia AB, Bioventure Hub, HE424, c/o AstraZeneca AB, R&D, Mölndal 43150, Sweden.
               2
                Department of Agricultural and Food Sciences, University of Bologna, Bologna 40127, Italy.
               3
                Protein Engineering and Evolution Unit, Okinawa Institute of Science, Technology Graduate University, Okinawa 40-0193,
               Japan.
               4
                Institut de Biologia Evolutiva (UPF-CSIC), Departament de Medicina i Ciències de la Vida, Universitat Pompeu Fabra, Parc de
               Recerca Biomèdica de Barcelona, Barcelona 08003, Spain.
               5
                Department for the Cultural Heritage (DBC), University of Bologna, Ravenna 48121, Italy.
               6
                Andlid Bio Solutions AB, Gothenburg 41871, Sweden.
               Correspondence to: Dr. Monica Modesto, Prof. Paola Mattarelli, Department of Agricultural and Food Sciences, University of
               Bologna, Viale Fanin 44, Bologna 40127, Italy. E-mail: monica.modesto@unibo.it; paola.mattarelli@unibo.it
               How to cite this article: D’Aimmo MR, Satti M, Scarafile D, Modesto M, Pascarelli S, Biagini SA, Luiselli D, Mattarelli P, Andlid T.
               Folate-producing bifidobacteria: metabolism, genetics, and relevance. Microbiome Res Rep 2024;3:11. https://dx.doi.org/10.
               20517/mrr.2023.59
               Received: 8 Oct 2023  First Decision: 3 Nov 2023  Revised: 11 Nov 2023  Accepted: 29 Nov 2023  Published: 12 Dec 2023
               Academic Editors: Christian Milani, Marco Ventura, Emma Allen-Vercoe  Copy Editor: Dong-Li Li  Production Editor: Dong-Li Li
               Abstract
               Folate (the general term for all bioactive forms of vitamin B ) plays a crucial role in the evolutionary highly
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               conserved one-carbon (1C) metabolism, a network including central reactions such as DNA and protein synthesis
               and methylation of macromolecules. Folate delivers 1C units, such as methyl and formyl, between reactants. Plants,
               algae, fungi, and many bacteria can naturally produce folate, whereas animals, including humans, must obtain
               folate from external sources. For humans, folate deficiency is, however, a widespread problem. Bifidobacteria
               constitute an important component of human and many animal microbiomes, providing various health advantages
               to the host, such as producing folate. This review focuses on bifidobacteria and folate metabolism and the current
               knowledge of the distribution of genes needed for complete folate biosynthesis across different bifidobacterial
               species. Biotechnologies based on folate-trophic probiotics aim to create fermented products enriched with folate
               or design probiotic supplements that can synthesize folate in the colon, improving overall health. Therefore,
               bifidobacteria (alone or in association with other microorganisms) may, in the future, contribute to reducing
               widespread folate deficiencies prevalent among vulnerable human population groups, such as older people, women
               at child-birth age, and people in low-income countries.

               Keywords: Bifidobacteria, folate metabolism, folate biofortification, gut microbiota

                           © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
                           International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
                           adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
               long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
               indicate if changes were made.

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