The role of iron in host–microbiota crosstalk and its effects on systemic glucose metabolism

Iron is critical for the appearance and maintenance of life on Earth. Almost all organisms compete or cooperate for iron acquisition, demonstrating the importance of this essential element for the biological and physiological processes that are key for the preservation of metabolic homeostasis. In humans and other mammals, the bidirectional interactions between the bacterial component of the gut microbiota and the host for iron acquisition shape both host and microbiota metabolism. Bacterial functions influence host iron absorption, whereas the intake of iron, iron deficiency and iron excess in the host affect bacterial biodiversity, taxonomy and function, resulting in changes in bacterial virulence. These consequences of the host–microbial crosstalk affect systemic levels of iron, its storage in different tissues and host glucose metabolism. At the interface between the host and the microbiota, alterations in the host innate immune system and in circulating soluble factors that regulate iron (that is, hepcidin, lipocalin 2 and lactoferrin) are associated with metabolic disease. In fact, patients with obesity-associated metabolic dysfunction and insulin resistance exhibit dysregulation in iron homeostasis and alterations in their gut microbiota profile. From an evolutionary point of view, the pursuit of two important nutrients — glucose and iron — has probably driven human evolution towards the most efficient pathways and genes for human survival and health.