Ex vivo folate production by fecal bacteria does not predict human blood folate status: Associations between dietary patterns, gut microbiota, and folate metabolism

Although some bacteria inhabiting the human gut synthesize folates, it has not yet been established whether bacterial folate biosynthesis can impact human folate status. The main objectives of this study were to evaluate associations between different lifestyle factors and the potential of fecal microbiota to produce folates, and to investigate whether this potential is associated with circulating folate and total homocysteine (tHcy) levels in humans. To this end, we carried out an observational study of two hundred adult participants, with high variance in dietary habits. Diet was determined using three-day food records. Fecal microbiota composition was assessed by 16S rRNA gene amplicon sequencing. To establish the folate-production potential of fecal bacteria, cultures containing feces were incubated under anaerobic conditions for 24 h, and the folate concentration was measured before and after incubation. The folate concentration in cultures was 185.4 ± 228.1 pg/ml/log(CFU/g) (2125.4 ± 2454.3 pg/ml) higher after incubation. This change in concentration was not associated with the healthy eating index that measures diet quality (r = -0.11, p = 0.11), but it was positively associated with low α-diversity (r = -0.18, p < 0.01), and high relative abundance of the Bacteroides, as well as Sutterella and Parasutterella genera. The gut microbiota's folate producing potential was associated neither with serum folate nor with plasma tHcy levels. In conclusion, some taxa of the native gut microbiota have the ability to synthesize folates under culture conditions, but this bacterial folate biosynthesis capacity does not predict human folate status.