Iron deficiency affects nearly one in four people worldwide, leading to anemia and the failure to maintain adequate tissue oxygenation, as well as other adverse effects. Research has shown that the gut microbiota plays a significant role in iron absorption and metabolism, and probiotics, prebiotics, and postbiotics have been studied as potential therapies for iron deficiency anemia.
A previous IPA blog described the research regarding a role for probiotics in iron deficiency anemia. Here the relevant evidence for prebiotics will be explored.
Iron deficiency anemia, in brief
Anemia is a condition in which the numbers of healthy red blood cells are insufficient to supply adequate oxygen to tissues. The most common cause is iron deficiency which is the result of a lack of dietary iron, poor iron absorption, blood loss, or pregnancy. Iron is vital for producing hemoglobin in red blood cells, energy production, immunity, muscle activity, and brain function. It can be obtained through dietary sources, supplements, or blood transfusions and exists in two forms, heme and non-heme, which can transform between Fe2+ and Fe3+.
Gut microbiota and iron
Only 10% of dietary iron is absorbed in humans, with absorption occurring in the duodenum and small intestine where iron combines with apoferritin to form ferritin, stored in the liver. The gut microbiota plays a critical role in iron homeostasis by reducing iron-binding compounds and converting Fe3+ to Fe2+, enhancing the host’s access to dietary iron. 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 show that Fe supplements can affect gut microbiota composition by increasing pathogenic Escherichia coli and reducing lactic acid bacteria (bifidobacteria and lactobacilli).
See the previous IPA blog Potential of Probiotics in Iron Deficiency for an expanded view of iron-deficiency anemia, its causes, and the interaction of the gut microbiota in iron bioavailability and metabolism.
Prebiotics in Iron Deficiency Anemia
Prebiotic: “A substrate that is selectively utilized by host microorganisms conferring a health benefit.”
Certain dietary fibers meet the criteria to be classified as prebiotics. Additionally, prebiotics can originate from non-fiber sources like polyphenols.
Prebiotics include fructooligosaccharides (FOS), galactooligosaccharides (GOS), inulin, glucans, pectins, and lactulose. These prebiotics are naturally found in foods and can also be produced as supplements.
Researchers have proposed a role for prebiotics in iron deficiency anemia based on several mechanisms: the ability of prebiotics and/or synbiotics to lower the pH of the colon, increasing the reduction of Fe3+ to Fe2+, promoting iron uptake by enterocytes, as well as the fermentation process that enhances SCFA production, which may contribute to increased colon absorption.
Several types of prebiotics and synbiotics have been studied in relation to iron deficiency anemia.
GOS is a non-digestible fiber formed from galactose, as lactose is cleaved by the enzyme b-galactosidase into glucose and galactose. About 90% of dietary GOS will pass into the colon, where bacteria can ferment it. GOSs can also be derived from lactulose.
Adding GOS during iron supplementation reduces destructive effects on the gut microbiota and has been shown to increase fractional iron absorption in women with iron deficiency. However, absorption enhancement depends on the format and the amount of elemental iron in the supplement. The addition of GOS to corn porridge enriched with iron increased iron absorption by 62% in infants. However, another study observed that a single dose of GOS added to a meal did not increase iron absorption in infants with anemia or iron deficiency, suggesting repeated feeding of GOS may be needed to enhance iron absorption at this age.
See this summary of human studies on prebiotics in anemia.
A group of oligosaccharides fermented in the colon, fructooligosaccharides (FOS) are found in several plants, including onion, chicory, garlic, asparagus, banana, and artichoke.
The bulk of studies examining a role for FOS in iron absorption has been done in rats. One study found that FOS improved iron bioavailability in anemic rats, as measured by hemoglobin and iron stores in the liver. FOS also prevented anemia in gastrectomy rats, possibly by acting in the large intestine.
The role of FOS in iron absorption in humans is not clear.
Inulin is a non-digestible polysaccharide, a mixture of linear fructose polymers with different chain length and a glucose molecule at each C2 end, produced by many types of plants, with chicory being the most frequent source for industrial extraction. Additional food sources include artichokes, asparagus, bananas, and onions.
In animals, the effect of inulin on iron absorption is mixed. One study observed increased iron absorption in rats after ingesting inulin, while another study did not observe any increase in iron absorption in anemic rats supplemented with inulin.
In a human trial with anemic women, inulin showed prebiotic activity but did not increase iron absorption.
An indigestible plant polysaccharide, pectin is found in many fruits, vegetables, legumes, and nuts, as well as in food additives. Pectin is easily degraded by gut bacteria and may function as a prebiotic.
Studies on the effect of pectin on iron absorption are limited. A 2022 review found that some studies found no significant difference in iron absorption with pectin supplementation, while others observed reduced iron bioavailability in infants fed with pectin-containing formula.
Synbiotics in Iron Deficiency Anemia
A synbiotic is “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host.”
In one study with rats, inulin (either short or long-chain) added to yogurt fortified with ferric sulfate increased the bioavailability of iron, with the highest effect observed with long-chain inulin. Another study looked at the in vitro (Caco-2 cell) effects of inulin on the availability of iron in milk and soy-based probiotic yogurts. The results suggested that while inulin did not have a direct effect on iron absorption, when used by cells, it had a positive impact. Furthermore, in a study conducted in iron-deficient children, a three-month regimen of iron supplementation along with a mixture of Lactiplantibacillus plantarum and fructooligosaccharides in fermented milk did not influence iron status or gut microbiota profile compared to controls.
Nanoparticles are being explored for their potential use in the prebiotic industry, as they can improve drug delivery and have antimicrobial effects. In one study, iron-pectin nanoparticles were used to deliver Lactiplantibacillus plantarum, and the results showed that iron did not affect the bacterial viability and was efficient in iron delivery and bacterial stabilization. Iron oxide nanoparticles, combined with pectin and lactic acid bacteria, are also being developed to protect microorganisms and safely deliver soluble iron to the intestine.
Various prebiotics, including fructooligosaccharides (FOS), galactooligosaccharides (GOS), and pectins, have been studied for their potential role in improving iron absorption and reducing iron deficiency anemia. However, the effects of these prebiotics on iron absorption in humans are inconsistent. Synbiotics, mixtures of live microorganisms and selectively utilized substrates, have also been studied for their potential role in improving iron absorption. In addition, nanoparticles are being explored for their potential use in the prebiotic industry, specifically for their ability to improve drug delivery and have antimicrobial effects.
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