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Oral Ferric Maltol Does Not Adversely Affect the Intestinal Microbiome of Patients or Mice, But Ferrous Sulphate Does
Awad Mahalhal1, Alessandra Frau1, Michael D Burkitt2
1Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GE, UK.
Background And Aims:
Altering dietary ferrous sulphate (FS) consumption exacerbates a murine model of colitis and alters the intestinal microbiome. We investigated the impact of oral ferric maltol (FM) and FS on mice with dextran sodium sulphate (DSS) induced colitis, and the microbiome of patients with iron deficiency.
Methods:
Mice had acute colitis induced, with 2% DSS for 5 days, followed by water. During this period, groups of mice were fed standard chow (200 ppm iron, SC, n = 8), or SC with 200ppm FS supplementation (n = 16, FSS), or SC with 200 ppm FM supplementation (n = 16, FMS). Clinical, pathological and microbiome assessments were compared at days 1 and 10. Fecal bacterial gDNA was extracted and the microbiome assessed by sequencing. Statistical inferences were made using MacQIIME. Principal Coordinates Analysis were used to visualize beta-diversity cluster analysis. Ten patients with IDA were treated with FS, and six with inactive inflammatory bowel disease received FM, supplements for four weeks: pre- and mid-treatment fecal samples were collected: the microbiome was assessed (see above).
Results:
In mice, after DSS treatment, there was a decrease in many genera in the SC and FSS groups: Lactobacillales increased in mice that received FMS. In humans, FS treatment led to an increase in five genera, but FM was not associated with any measurable change. The severity of DSS-induced colitis was greater with FSS than FMS.
Conclusions:
This study demonstrates differential and unique influences of ferric maltol and ferrous sulphate supplements on intestinal microbiota. These differences might contribute to the different side effects associated with these preparations.
Insights
Ferric maltol (FM) and ferrous sulphate (FS) supplements uniquely impact the gut microbiome and colitis severity in mice. FM supplementation showed a protective effect in DSS-induced colitis, unlike FS.
Area of Science:
- Gastroenterology
- Microbiome Research
- Pharmacology
Background:
- Dietary iron supplementation, specifically ferrous sulphate (FS), can worsen colitis and alter the gut microbiome.
- Understanding the differential effects of iron supplements is crucial for managing gastrointestinal conditions.
Purpose of the Study:
- To investigate the impact of oral ferric maltol (FM) and FS on dextran sodium sulphate (DSS)-induced colitis in mice.
- To assess the effects of FM and FS on the intestinal microbiome in both a murine model and human patients with iron deficiency.
Main Methods:
- Mice with DSS-induced colitis were supplemented with standard chow, FS, or FM.
- Clinical, pathological, and microbiome assessments were performed.
- Human patients with iron deficiency anemia (IDA) or inactive inflammatory bowel disease (IBD) received FS or FM, respectively, with microbiome analysis.
Main Results:
- In mice, FS supplementation exacerbated DSS-induced colitis, while FM supplementation increased beneficial Lactobacillales.
- FS treatment in humans led to an increase in five bacterial genera, whereas FM showed no significant microbiome changes.
- Colitis severity was greater in mice treated with FS compared to FM.
Conclusions:
- Ferric maltol and ferrous sulphate exhibit distinct effects on the intestinal microbiota.
- These differences in microbiome modulation may explain the varying side effect profiles of FM and FS.
