Numerous microorganisms – especially intracellular pathogens and red blood cell parasites – can influence iron metabolism, leading to anaemia, functional iron deficiency or reduced iron bioavailability. Lyme borreliosis and frequently associated pathogens – such as Babesia, Bartonella, or other tick-borne pathogens – have also been suggested to influence iron metabolism. However, based on current evidence, the mechanisms differ from those of classic iron deficiency: in many cases, it is more a matter of inflammation-mediated iron redistribution and functional iron deficiency rather than primary intestinal malabsorption.
Inflammatory regulation of iron metabolism
The central regulator of iron homeostasis is hepcidin, a peptide hormone produced in the liver. Hepcidin binds to a protein called ferroportin, which exports iron, and inhibits the release of iron from cells, including enterocytes and macrophages. As a result, the amount of iron absorbed from the intestine decreases and iron is stored in the cells.
In inflammatory conditions, such as Lyme disease, hepcidin levels rise, resulting in hypoferraemia and the development of anaemia characteristic of chronic diseases.
This mechanism is not true iron deficiency, but rather a functional iron deficit, where the body’s iron stores are intact, but the iron is not available for erythropoiesis.
The Lyme disease pathogen is unique in that it does not require iron for growth, unlike most bacteria. Instead, it uses other metal ions (e.g. manganese) in its metabolic processes.
Role of co-infections
Several of the pathogens commonly associated with Lyme disease more directly affect red blood cells or iron metabolism.
Babesia
Babesia species are intraerythrocytic parasites that cause haemolysis and anaemia through a mechanism similar to that of malaria. This results in:
- red blood cell destruction
- increased iron loss
- and often low ferritin.
The clinical picture may therefore mimic true iron deficiency.
Bartonella
Bartonella is a bacterium that exhibits endothelium and erythrocyte tropism. During infection:
- chronic inflammation
- endothelial dysfunction
- and immune activation
develop, which can also push iron metabolism towards anaemia.
Iron absorption disorder or functional iron deficiency?
Based on the current literature, three different mechanisms should be distinguished:
- Inflammation-induced functional iron deficiency
- high hepcidin
- decreased iron absorption and iron release
- normal or elevated ferritin
- Haemolytic anaemia in co-infections (e.g. Babesia)
- Red blood cell destruction
- secondary iron metabolism changes
- True iron deficiency
- due to chronic disease, blood loss or malabsorption
In Lyme disease and co-infections, the most common mechanism is not primary malabsorption, but hepcidin-mediated iron redistribution, which functionally reduces iron availability.
Summary
Based on current research, Borrelia infection alone rarely causes classic intestinal iron absorption disorders. However, the inflammation triggered by the infection can significantly affect iron metabolism. The pathogen triggers immune activation, which causes an increase in hepcidin and, as a result, a decrease in serum iron and iron bioavailability.
Infections associated with Lyme disease, especially red blood cell parasites such as Babesia, can cause further haematological abnormalities and true iron deficiency. Thus, in clinical practice, iron deficiency laboratory results in Lyme disease patients may be the result of several different pathophysiological mechanisms.
Sources:
https://pubmed.ncbi.nlm.nih.gov/31949017/
https://pubmed.ncbi.nlm.nih.gov/23061404/
(C) Lyme Borreliosis Foundation
