Effects of iron deficiency and iron supplementation at the host-microbiota interface: Could a piglet model unravel complexities of the underlying mechanisms?

Abstract

Iron deficiency is the most prevalent human micronutrient deficiency, disrupting the physiological development of millions of infants and children. Oral iron supplementation is used to address iron-deficiency anemia and reduce associated stunting but can promote infection risk since restriction of iron availability serves as an innate immune mechanism against invading pathogens. Raised iron availability is associated with an increase in enteric pathogens, especially Enterobacteriaceae species, accompanied by reductions in beneficial bacteria such as Bifidobacteria and lactobacilli and may skew the pattern of gut microbiota development. Since the gut microbiota is the primary driver of immune development, deviations from normal patterns of bacterial succession in early life can have long-term implications for immune functionality. There is a paucity of knowledge regarding how both iron deficiency and luminal iron availability affect gut microbiota development, or the subsequent impact on immunity, which are likely to be contributors to the increased risk of infection. Piglets are naturally iron deficient. This is largely due to their low iron endowments at birth (primarily due to large litter sizes), and their rapid growth combined with the low iron levels in sow milk. Thus, piglets consistently become iron deficient within days of birth which rapidly progresses to anemia in the absence of iron supplementation. Moreover, like humans, pigs are omnivorous and share many characteristics of human gut physiology, microbiota and immunity. In addition, their precocial nature permits early maternal separation, individual housing, and tight control of nutritional intake. Here, we highlight the advantages of piglets as valuable and highly relevant models for human infants in promoting understanding of how early iron status impacts physiological development. We also indicate how piglets offer potential to unravel the complexities of microbiota-immune responses during iron deficiency and in response to iron supplementation, and the link between these and increased risk of infectious disease.

The Effect of Oral Iron Supplementation/Fortification on the Gut Microbiota in Infancy: A Systematic Review and Meta-Analysis

“…Iron deficiency is negatively correlated to behavioral, cognitive, and motor development, as well as impaired immune responses [1,3,7,[13][14][15][16][17][18]. Ensuring iron adequacy is critical, as iron deficiency anemia in infancy is associated with neurodevelopmental and cognitive delay that persists even if optimal iron levels are achieved [7,17,18]. By the age of 6 months, breastfed infants are dependent on supplementary solid foods as sources of iron [7,14,26,44,47].…”

“…Ensuring iron adequacy is critical, as iron deficiency anemia in infancy is associated with neurodevelopmental and cognitive delay that persists even if optimal iron levels are achieved [7,17,18]. By the age of 6 months, breastfed infants are dependent on supplementary solid foods as sources of iron [7,14,26,44,47]. In order to prevent iron deficiency, oral iron supplementation and fortification are often required [5,[9][10][11][12].…”

“…Iron is essential for the growth and development of the human body [1][2][3][4]. It is involved in various biological processes due to its ability to act as an electron receptor or electron donor [1][2][3][5][6][7].…”

Effect of Additional Iron Injection to Suckling Pigs on Hematocrit Level during the Suckling Period

“…The suckling piglet has high daily iron requirement at 7 to 16 mg per d during the suckling period with a fast growth rate over 250 g per d [ 1 , 2 ]. However, the sow milk contains 0.2–4 mg iron per L with the 60–90% absorption rate, which result in approximately 1 mg iron/d absorbed by the piglets [ 1 , 20 ]. This indicates that the piglets could not meet their daily iron requirement over the suckling period and need an iron injection at birth.…”

Iron Supplementation of Pregnant Sows to Prevent Iron Deficiency Anemia in Piglets: A Procedure of Questionable Effectiveness

“…High oral iron doses or inappropriate supplementation protocols can also disrupt the gut microbiota in pregnant sows, potentially leading to dysbiosis and associated gastrointestinal disorders [42]. Maintaining gut health is crucial for optimal nutrient utilization and the well-being of both the mother and developing piglets.…”