Cairo, Egypt – A groundbreaking study has emerged from the bustling city of Cairo, where an impressive collaborative effort among researchers has paved the way for a significant advancement in the field of probiotics and folic acid production. With folic acid being an essential vitamin for numerous bodily functions, particularly in pregnant women for the proper development of the fetus, this discovery has the potential to have far-reaching effects on nutritional science and public health.

The study, titled “FolE gene expression for folic acid productivity from optimized and characterized probiotic Lactobacillus delbrueckii,” presents an in-depth analysis of seven lactic acid bacterial strains (LAB) derived from milk. The researchers identified Lactobacillus delbrueckii as a standout probiotic candidate with numerous health-promoting properties, with the KH1 isolate being the most prolific producer of folic acid.

With a production rate of 100 µg/ml of folic acid after just 48 hours of incubation, KH1 showed an impressive three-fold increase in FolE gene expression after 24 hours when compared to other isolates. Lactose was determined to be the best carbon source for folic acid production, not just for the star KH1 isolate, but also for its fellow contenders, KH80 and KH98.

The study’s meticulosity extended to the identification of the selected LAB isolates through 16S rDNA sequencing as Lactobacillus delbrueckii. Their resilience was proven, with high tolerance at acidic pH levels between 2 and 3, as well as resistance to varying concentrations of bile salts. Remarkably, isolate KH1 also showed a 99% scavenging activity, suggesting a strong antioxidant capability.

Perhaps one of the study’s most innovative approaches was the use of a docking study to investigate the binding mode of folic acid against dihydrofolate reductase (DHFR). This study discovered significant interactions between folic acid and key amino acids within DHFR, demonstrating the intricate interplay and the potential for folic acid supplementation to influence hemoglobin levels.


Researchers from various Egyptian universities and institutes teamed up—to a large extent—due to the increasing interest in probiotics as a means of improving health and nutrition. The explosive growth of antibiotic resistance and the shift towards natural health remedies have intensified the search for new and natural sources of essential vitamins.

Lactobacillus delbrueckii, being a common inhabitant of the gastro-intestinal tract, has well-documented benefits ranging from antibiotic companionship to prevention of gastrointestinal disorders. Nonetheless, its role in fortifying essential nutrients, such as folic acid, had not been thoroughly explored until now.

Folic acid, or vitamin B9, plays a vital role in synthesizing and repairing DNA, promoting proper brain function, and supporting fetal development during pregnancy. Deficiency in this vitamin can lead to anemia and, in pregnant women, an increased risk of neural tube defects in newborns.

The researchers isolated the LAB strains from milk samples and subjected them to rigorous testing to determine their proclivity for folic acid production. They measured FolE gene expression, which is critical for the biosynthesis of folate, and assessed the resistance of the bacteria to acidity and high bile salt concentrations, mimicking conditions in the human gastrointestinal tract.

Additionally, they conducted antioxidant assays to gauge the strains’ ability to neutralize free radicals—a measure of their anticipated health benefits. Through computational docking studies, they also elucidated the potential mechanism of folate interaction with human DHFR, a key enzyme in the folate pathway.


A standout finding of the research was the impressive folic acid production by the KH1 isolate, quantifying the fruitful expression of the FolE gene. These results hinted at the bacterium’s suitability for folic acid biosynthesis at an industrial scale.

The study’s in vitro findings suggested that Lactobacillus delbrueckii, in general, bore strong probiotic properties, further evidenced by the antioxidative activities noted, similar to those of ascorbic acid—a known antioxidant.

In computational docking simulations, folic acid exhibited a strong affinity for binding to human DHFR, forming stabilizing interactions like hydrogen bonds and hydrophobic interactions. These findings hinted at a biological synergy between the folic acid produced by these bacteria and human metabolic pathways.

The results of the KH1 isolate are particularly noteworthy, showing not just efficacy in folic acid production but also resilience under harsh conditions similar to the human stomach and intestines. This confluence of traits underscores its potential utility in dietary supplements.

Moreover, the docking study bridges a significant gap in understanding how the folic acid produced by these bacteria could be effectively utilized within the human body. By demonstrating that the folic acid interacts favorably with human DHFR, the researchers have provided a molecular rationale for using these bacterial strains as a natural dietary supplement.

The researchers also posit that fortifying foods with these Lactobacillus delbrueckii strains could be a pragmatic way to tackle folate deficiency, which remains a global health concern.


The comprehensive efforts of Khedr Mohamed M and his colleagues have uncovered a promising avenue for natural folic acid production. Their research highlights the interplay between probiotics and human health, not only in terms of disease prevention but also in nutrient synthesis.

As the demand for health-promoting ingredients in foods intensifies, this research opens the door to enhancing the nutritional value of dairy products with probiotic Lactobacillus delbrueckii strains. The potential these findings hold for improving public health, particularly among pregnant women, cannot be overstated.

Future research could explore the scalability of folic acid production using Lactobacillus delbrueckii and investigate the long-term benefits of consuming these probiotics. With an increasingly health-conscious public, and mounting evidence of the gut microbiome’s critical role in overall health, the outcomes of this study are set to influence both science and industry for years to come.


  • Chugh B, Kamal-Eldin A. Bioactive compounds produced by probiotics in food products. Curr Opin Food Sci. 2020;32:76–82. doi: 10.1016/j.cofs.2020.02.003. 10.1016/j.cofs.2020.02.003
  • Pop OL, Socaci SA, Suharoschi R, Vodnar DC. Pro and prebiotics foods that modulate human health. The Role of Alternative and Innovative Food Ingredients and Products in Consumer Wellness. 2019. pp. 283–313.
  • Jaiswal M, Sharma R, Subramani S, Mishra V, Sharma J, Parthasarathy P, Bisen PS, Raghuwanshi S. Role of Lactobacilli as probiotics in human health benefits: current status and future prospects. Journal of Biotechnology and Biochemistry. 2020;6:19–24.
  • Behera SS, Ray RC, Zdolec N. Lactobacillus plantarum with functional properties: an approach to increase safety and shelf-life of fermented foods. Biomed Res Int. 2018;2018:9361614. doi: 10.1155/2018/9361614. 10.1155/2018/9361614 PMC5994577 29998137
  • Jurášková D, Ribeiro SC, Silva CCG. Exopolysaccharides produced by lactic acid bacteria: from biosynthesis to health-promoting properties. Foods. 2022;11(2):156. doi: 10.3390/foods11020156. 10.3390/foods11020156 PMC8774684 35053888
  • Jiang S, Cai L, Lv L, Li L. Pediococcus pentosaceus, a future additive or probiotic candidate. Microb Cell Fact. 2021;20:45. doi: 10.1186/s12934-021-01537-y. 10.1186/s12934-021-01537-y PMC7885583 33593360
  • Sestito S, D’Auria E, Baldassarre ME, Salvatore S, Tallarico V, Stefanelli E, Tarsitano F, Concolino D, Pensabene L. The role of prebiotics and probiotics in prevention of allergic diseases in infants. Front Pediatr. 2020;8:583946. doi: 10.3389/fped.2020.583946. 10.3389/fped.2020.583946 PMC7783417 33415087
  • Zhang T, Zhang C, Zhang J, Sun F, Duan L. Efficacy of probiotics for irritable bowel syndrome: a systematic review and network meta-analysis. Front Cell Infect Microbiol. 2022;12:859967. doi: 10.3389/fcimb.2022.859967. 10.3389/fcimb.2022.859967 PMC9010660 35433498
  • Feng Xiao MM, Zhuang LiJuan MM, Ling Chen MM, Zhao Hongying MM, Huang Rui MM, Guo ZhiFeng MM. Comparison of different probiotics in the treatment of acute diarrhea in children: a protocol for systematic review and network meta-analysis. Medicine. 2022;101(11):e28899. PMC10684214 35356899
  • Blaabjerg S, Artzi DM, Aabenhus R. Probiotics for the prevention of antibiotic-associated diarrhea in outpatients-a systematic review and meta-Analysis. Antibiotics [Basel] 2017;6(4):21.

Categorized in:

Health News,

Last Update: January 18, 2024