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Page 2 of 22 D’Aimmo et al. Microbiome Res Rep 2024;3:11 https://dx.doi.org/10.20517/mrr.2023.59

INTRODUCTION
Folate, also known as vitamin B , belongs to the water-soluble B-vitamin family. The IUPAC-IUB Joint
9
[1]
Commission on Biochemical Nomenclature (JCBN) suggested the use of the term folate for each member
of the family of pteroylglutamates or a combination of them, with different levels of oxidation of the
pteridine ring, one-carbon substitutions and numbers of glutamate units. Folic acid, in particular, should
only be used when referring to the synthetic form of vitamin B .
[2]
9
Folate is an essential vitamin implicated in pivotal metabolic pathways. Without folate, cells cannot properly
synthesize or methylate DNA and proteins. Many microorganisms and plants can obtain folate de novo,
whereas vertebrates and other animals, such as insects, need to obtain folate via nutritional sources .
[3]
Understanding that sufficient folate intake reduces the risk for neural tube defects (NTD) is considered one
of the most important health-related discoveries ever made . Folate deficiency, instead, has been linked to
[4]
several health disorders, such as coronary heart disease, osteoporosis, Alzheime’rs disease, and colorectal
cancer . Moreover, folate deficiency causes anemia because it is required for red blood cell production. In
[5]
general, folate requirement is higher during rapid cell division and growth periods, such as throughout
infancy and pregnancy .
[6]
Folate naturally occurs in leafy green vegetables, oranges, beans, rice, and liver. Natural forms of folates can
also be produced by many microorganisms commonly present in the gastrointestinal microbiota, such as
bifidobacteria, lactobacilli, and yeasts . These forms of folate can be absorbed and utilized by animal or
[7]
human hosts. Folate is absorbed via transporters in the gastrointestinal epithelia, and through the
circulatory system, it then reaches the liver, where it may be stored. The human diet varies in folate content
and bioavailability, and there is a substantial loss during processing, storage, and cooking. Therefore, the
suggested targets for daily folate intake are often uncertain.

Nevertheless, the World Health Organization recommends that pregnant women adhere to a healthy,
balanced diet and take 0.4 mg of the folic acid supplement daily to ensure a healthy pregnancy and improve
pregnancy outcomes . For this reason, several health authorities have proposed mandatory food
[8]
fortification with synthetic folic acid. For example, when used as a fortificant in cereals and bread, folic acid
can be considered cost-efficient in production, more stable than natural food folate, and superior in terms
of bioavailability and bioefficacy. In Australia, food fortification has been implemented since 2009, and in
the USA and Canada since 1998, and in both cases, rates of incidence of NTDs have dramatically
declined . Nevertheless, fortification is questioned because a high synthetic folic acid intake could be
[6,9]
involved in promoting subclinical cancers and other adverse health effects . For this reason, Scandinavia
[10]
has chosen not to implement folate fortification. In Europe, there are no legal obligations in food
[11]
fortification. However, in 2014, the European Food Safety Authority urged women of childbearing age to
fortify their diets with folates.

A safe complement to fortification with the potential to make a difference in folate status among vulnerable
groups is fermentation with strains selected to produce folate during the fermentation process and/or in the
human gastrointestinal tract [12-15] . A high folate biosynthesis capacity was found in certain species and strains
of the genus Bifidobacterium and some yeasts. Therefore, fortification programs utilizing folate-producing