Systemic iron reduction by venesection alters the gut microbiome in patients with haemochromatosis

Abstract Background & Aims Iron reduction by venesection has been the cornerstone of treatment of Hemochromatosis for decades; its reported health benefits are many. Repeated phlebotomy can lead to a compensatory increase in intestinal iron absorption, reducing intestinal iron availability. As most gut bacteria are highly dependent on iron for survival, we postulated that by reducing gut iron levels, venesection could alter the gut microbiota. Methods: Clinical parameters, faecal bacterial composition and metabolomes were assessed before and during treatment in a group of Haemochromatosis patients undergoing iron reduction therapy. Results: Here we show that systemic iron reduction is associated with an alteration of the gut microbiome, with changes evident in those who experienced reduced faecal iron availability with venesection. For example, levels of F. prausnitzii, a bacteria associated with improved colonic health, were increased by faecal iron reduction. Similarly, metabolomic changes were seen in association with reduced faecal iron levels. Conclusion: These findings highlight a significant shift in the gut microbiome of patients who experience reduced colonic iron during venesection. Targeted depletion of faecal iron may represent a novel therapy for metabolic and inflammatory diseases, meriting further investigation.