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

Abstract

Venesection is the cornerstone of haemochromatosis treatment. Venesection leads to a compensatory increase in intestinal iron absorption. Reduced faecal iron availability leads to shifts in human colonic microbial composition. Changes in the human colonic metabolome occur with reduced faecal iron availability. Lay summary Iron depletion by repeated venesection is the mainstay of treatment for haemochromatosis, an ironoverload disorder. Venesection has been associated with several health benefits, including improvements in liver function tests, reversal of liver scarring, and reduced risk of liver cancer. During iron depletion, iron absorption from the gastrointestinal (GI) tract increases to compensate for iron lost with treatment. Iron availability is limited in the GI tract and is crucial to the growth and function of many gut bacteria. In this study we show that reduced iron availability in the colon following venesection treatment leads to a change in the composition of the gut bacteria, a finding that, to date, has not been studied in patients with haemochromatosis.

Hemochromatosis: Ferroptosis, ROS, Gut Microbiome, and Clinical Challenges with Alcohol as Confounding Variable

“…Further research is viewed as unlikely to change the confidence in the estimate of the benefit and risk of venesection in this disease [ 63 ]. Consensus among experts exists that venesection is the first-line therapy for patients with hemochromatosis with similar proposals for how best to proceed [ 63 , 82 ]. As an example of qualification for venesection, patients should have a serum ferritin level >300 μg/L in men and >200 μg/L in women in combination with an elevated fasting transferrin saturation (>45%) for both men and women.…”

“…As an example of qualification for venesection, patients should have a serum ferritin level >300 μg/L in men and >200 μg/L in women in combination with an elevated fasting transferrin saturation (>45%) for both men and women. Weekly or fortnightly venesection aims to achieve an initial serum ferritin target of 50–100 μg/L [ 82 ]. Each venesection typically removes 500 mL of blood, corresponding to 250 mg of iron [ 82 ].…”

“…Weekly or fortnightly venesection aims to achieve an initial serum ferritin target of 50–100 μg/L [ 82 ]. Each venesection typically removes 500 mL of blood, corresponding to 250 mg of iron [ 82 ]. Venesection intervals are increased, or a lower volume of blood is removed if the patient does not tolerate phlebotomy because of weakness, hypotension, or the development of anemia [ 82 ].…”

“…Each venesection typically removes 500 mL of blood, corresponding to 250 mg of iron [ 82 ]. Venesection intervals are increased, or a lower volume of blood is removed if the patient does not tolerate phlebotomy because of weakness, hypotension, or the development of anemia [ 82 ]. Venesection ameliorates overall prognosis but must be conducted throughout the whole patient life but mostly with reduced intervals [ 9 , 10 , 63 ].…”

The Role of Ferritin in Health and Disease: Recent Advances and Understandings

“…As regular and adequate iron supply through diet is critical for both, intense competition for the metal prevails between the host and microbes. Numerous studies have shown that iron availability influences the gut microbiome composition and function [ 86 , 87 , 88 , 89 , 90 ]. Human studies representing various geographic and pathologic backgrounds show that modulation of dietary iron levels influences links gut microbiome with the etiopathogenesis of a variety of disorders like dysbiosis, inflammation, and colorectal cancer [ 91 , 92 , 93 , 94 ].…”