Page 166 - Read Online

D’Aimmo et al. Microbiome Res Rep 2024;3:11 https://dx.doi.org/10.20517/mrr.2023.59 Page 9 of 22

of L. rhamnosus on external folate for growth see paragraph “Analysis of folate” for an explanation of the
theory behind microbiological assay). However, more recently, some strains of Lactiplantibacillus
[66]
plantarum and Latilactobacillus sakei have been found capable of synthesizing folate . Many studies have
focused on folate production by bifidobacteria but have not explored their potential to raise folate content
when added to food products .
[67]
Although increased folate levels in food products are possible with careful selection of strains, these levels
may remain lower than the recommended daily allowance (0.2 mg of folate) . For example, when
[68]
consuming 100 g of yogurt containing folate-producing probiotics, only the minimum required folate intake
for an adult may be achieved (about 15% of the minimum recommended dose). Therefore, it is important to
highlight the right food quantity and variety that have to be added to the diet to meet requirements.

Our microbiome has been put forward as a nutrition source for preventing low-folate conditions. However,
this potential has been hindered by the partial characterization of folate-secreting intestinal bacterial strains.
Indeed, while some studies have evaluated probiotic strains of Bifidobacterium spp. and Lactobacillus spp.,
as previously mentioned, little is known about the capacity of gut microbiomes to generate folate.

While all Eubacteria and Eukarya require folate, some Archaea (Methanobacterium thermoautotrophicum,
M. thermoautotrophicum, and Sulfolobus solfataricus) do not and may have evolved alternative pathways for
[69]
purine biosynthesis . Recent data show alternative non-folate carbon group carriers in Archaea in
metabolic steps where folate is required in bacteria and Eucaryota.

Engevik et al. showed folate biosynthesis as a major biochemical feature of the human intestinal
microbiome . Four metabolic modules in folate biosynthesis (chorismate, pABA, pterin, and folate
[70]
synthesis) have been described in terms of prevalence in a reference set of 512 microbial genomes accredited
to the human gastrointestinal tract. The gene distribution was studied among six phyla of the human
microbiome: Actinobacteriota, Bacteroidetes, Firmicutes, Proteobacteriota, Fusobacteriota, and
Verrucomicrobiota.

The authors found that 13.3% of the bacterial reference genomes contain genes involved in de novo
synthesis of THF. Therefore, the gut microbiome can be considered a folate-generating “organ”. The
remaining genomes (circa 87%) require folate or folate intermediates from other bacteria or the human diet.

Engevik’s and colleagues’ data were consistent with previous genomic studies that predicted 79% of
Fusobacteria, 71% of Proteobacteria, 26% of Actinobacteria, and 15% of Firmicutes in the human intestinal
microbiome can produce folate de novo.

In a study by Magnúsdottir et al., the genomes of 256 common human gut bacteria were assessed for
biosynthesis pathways for eight B vitamins (including folate) using the PubSEED platform . It was
[71]
predicted that 40%-65% of the gut microbiota could produce each of these vitamins. The authors
hypothesized that the coevolution of the human gut microbiota led to the shared B-vitamin biosynthesis
capability among these bacteria. Their data showed that the folate biosynthesis pathway was present in
nearly all Bacteroidetes genomes and most Fusobacteriota and Proteobacteria. However, genes for folate
synthesis were rare in the genomes of Actinobacteria and Firmicutes groups, mostly because of the absence
of the pABA biosynthesis pathway. They speculated that the human microbiome could synthesize 37% of
the daily recommended folate intake for non-pregnant, non-breastfeeding adults.