More than two billion people across the globe — primarily pregnant women and young children in developing countries—are deficient in iron, an essential trace mineral. Deficiency can lead to anemia, resulting in the failure to sustain suitable tissue oxygenation and body homeostasis.
According to research, the gut microbiota (GM) influences both the absorption and metabolism of iron. Conversely, iron fluctuations can also disrupt the homeostasis of the GM.
Probiotics, prebiotics, and postbiotics have been studied as potential therapeutic agents in iron deficiency anemia (IDA).
This blog will describe the latest findings pertaining to a role for probiotics. Subsequent articles will address the influence of prebiotics and postbiotics in IDA.
Iron deficiency anemia, explained
Anemia: a condition in which the number of red blood cells or the hemoglobin concentration within them is lower than normal.
Anemia is most commonly due to iron deficiency, which can be caused by:
- Lack of dietary iron. Foods rich in iron include eggs, meat, leafy green vegetables, and iron-fortified foods.
- Poor iron absorption, which can be caused by disease and small intestine resections
- Blood loss as with heavy menstrual periods and gastrointestinal bleeding
- Pregnancy, which requires increased iron
Iron is an essential component of hemoglobin, a protein in red blood cells that transports oxygen from the lungs to the rest of the body. It is also crucial for energy production, immunity, muscle activity, and brain function. Treatment includes providing dietary sources, supplements, or blood transfusions.
Dietary iron exists in two forms: heme iron (Fe2+) and non-heme iron (Fe3+), with transformation between these two states.
Gut microbiota and iron
A mere 10% of iron consumed through the diet is absorbed in humans, while the rest is eliminated through feces. The absorption of dietary iron only occurs in the form of Fe2+ ions and takes place in the duodenum and small intestine. Within the intestinal mucosa, iron combines with apoferritin to form ferritin, which is then stored in the liver. The iron in ferritin takes on the form of Fe3+ ions. In the bloodstream, transferrin binds to iron and facilitates its transportation throughout the body.
Both deficiency and excess iron have deleterious effects, so physiological iron homeostasis is tightly regulated.
The gut microbiota enhances the host’s access to dietary iron through two mechanisms: first, by reducing the concentration of iron-binding compounds in the gut, and second, by converting Fe3+ to Fe2+, the absorbable ion form.
Evidence suggests that mechanisms involved in the role of the gut microbiota in iron homeostasis include the production of short-chain fatty acids and other metabolites, enhanced iron uptake via increased mucin production, and improved anti-inflammatory immune response.
Iron levels in the body can influence the composition of gut microbiota, with both iron deficiency and excess fostering dysbiosis and the development of intestinal pathologies.
Studies on rats have shown that iron deficiency can cause bacterial translocation in the intestine. Adequate iron levels in the intestine can reduce the colonization and virulence of pathogenic microorganisms.
According to a 2017 review of studies in infants and young children, consumption of Fe supplements increases Fe in the large intestine. Consequently, supplementation affects the composition of gut microbiota by reducing the amount of lactic acid bacteria (bifidobacteria and lactobacilli) and increasing pathogenic Escherichia coli, which is associated with intestinal inflammation.
Probiotics and Iron Deficiency Treatment
Due to the role of gut microbiota in regulating iron balance, probiotics have been suggested as a potential strategy to enhance iron absorption and alleviate deficiency.
A study in rats tested the effects of an oral multispecies probiotic administered in high and low doses. Results revealed that probiotic supplementation exerted a “dose-independent and beneficial effect on iron bioavailability and duodenal iron.”
A 2019 meta-analysis reported that of the seven human clinical trials testing a range of probiotic species on iron status, “only one study supplementing with a strain of Lactiplantibacillus plantarum showed improvement in serum iron; no other studies reported improvement in iron status-related indices with probiotic treatment.” The authors suggested that the enhanced iron absorption was due to a higher reduction of ferric iron to a bioavailable form, improved iron uptake by enterocytes, and an anti-inflammatory immune response.
However, in one clinical trial, the same strain of Lactiplantibacillus plantarum administered to pediatric patients showed no difference in iron levels in children with IDA treated with iron supplements alone and those treated with probiotics. Despite this result, it is known that Limosilactobacillus fermentum displays an impressive ferric-reducing activity, which is required for iron absorption in the gastrointestinal tract and may prove to be beneficial in IDA.
A Table available online outlines the primary studies concerning iron absorption when single or multiple probiotic strains are administered.
Takeaway
Iron deficiency is a global problem that can lead to anemia. The gut microbiota plays a crucial role in both the absorption and metabolism of iron. Probiotics have been studied as potential therapeutic agents in iron deficiency anemia (IDA). Studies on rats have shown that probiotics can enhance iron bioavailability and alleviate deficiency. However, human clinical trials have been inconclusive. Lactiplantibacillus plantarum has shown some promising results in improving serum iron, while Limosilactobacillus fermentum displays ferric-reducing activity that may prove beneficial in IDA. The iron level in the body can influence the composition of gut microbiota, with both iron deficiency and excess having significant impacts on dysbiosis and the development of intestinal pathologies. The use of probiotics to improve iron homeostasis requires additional research.
Note: Future blogs will explore the influence of prebiotics and postbiotics in IDA.
Key references
Balamurugan, Ramadass et al. “Low levels of faecal lactobacilli in women with iron-deficiency anaemia in south India.” The British journal of nutrition vol. 104,7 (2010): 931-4. doi:10.1017/S0007114510001637
Bielik, Viktor, and Martin Kolisek. “Bioaccessibility and Bioavailability of Minerals in Relation to a Healthy Gut Microbiome.” International journal of molecular sciences vol. 22,13 6803. 24 Jun. 2021, doi:10.3390/ijms22136803
González, Ana et al. “Identification of the key excreted molecule by Lactobacillus fermentum related to host iron absorption.” Food chemistry vol. 228 (2017): 374-380. doi:10.1016/j.foodchem.2017.02.008
Hoppe, Michael et al. “Freeze-dried Lactobacillus plantarum 299v increases iron absorption in young females-Double isotope sequential single-blind studies in menstruating women.” PloS one vol. 12,12 e0189141. 13 Dec. 2017, doi:10.1371/journal.pone.0189141
Mack, D R et al. “Extracellular MUC3 mucin secretion follows adherence of Lactobacillus strains to intestinal epithelial cells in vitro.” Gut vol. 52,6 (2003): 827-33. doi:10.1136/gut.52.6.827
Ng, Oliver. “Iron, microbiota and colorectal cancer.” Wiener medizinische Wochenschrift (1946) vol. 166,13-14 (2016): 431-436. doi:10.1007/s10354-016-0508-4
Paganini, Daniela, and Michael B Zimmermann. “The effects of iron fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review.” The American journal of clinical nutrition vol. 106,Suppl 6 (2017): 1688S-1693S. doi:10.3945/ajcn.117.156067
Rosen, Gerald M et al. “Use of a Probiotic to Enhance Iron Absorption in a Randomized Trial of Pediatric Patients Presenting with Iron Deficiency.” The Journal of pediatrics vol. 207 (2019): 192-197.e1. doi:10.1016/j.jpeds.2018.12.026
Rusu, Ioana Gabriela et al. “Iron Supplementation Influence on the Gut Microbiota and Probiotic Intake Effect in Iron Deficiency-A Literature-Based Review.” Nutrients vol. 12,7 1993. 4 Jul. 2020, doi:10.3390/nu12071993
Silva, Bruno, and Paula Faustino. “An overview of molecular basis of iron metabolism regulation and the associated pathologies.” Biochimica et biophysica acta vol. 1852,7 (2015): 1347-59. doi:10.1016/j.bbadis.2015.03.011
Skrypnik, Katarzyna et al. “The Effect of Multispecies Probiotic Supplementation on Iron Status in Rats.” Biological trace element research vol. 192,2 (2019): 234-243. doi:10.1007/s12011-019-1658-1
Vonderheid, Susan C et al. “A Systematic Review and Meta-Analysis on the Effects of Probiotic Species on Iron Absorption and Iron Status.” Nutrients vol. 11,12 2938. 3 Dec. 2019, doi:10.3390/nu11122938