Do Iron Supplements Impact the Gut Microbiome of Women of Reproductive Age?

Not Applicable

Completed

• Conditions: Iron-deficiency; Microbial Colonization; Anemia
• Interventions: Dietary Supplement: Ferrous Fumarate; Dietary Supplement: Placebo

• Registration Number: NCT05033483
• Lead Sponsor: South Australian Health and Medical Research Institute

Brief Summary

In this randomised controlled trial the investigators will determine whether taking iron supplements compared to placebo for 21 days alters the bacteria (microbiome) in the large intestine of non-pregnant female participants.

Detailed Description

BACKGROUND: Many women take iron-containing supplements during pregnancy. Indeed, the World Health Organization recommends that all pregnant women in low-income countries take an iron supplement containing 60 mg/day of elemental iron to reduce iron deficiency and iron-deficiency anaemia. However, oral iron has poor bioavailability, less than 10% absorbed with the remainder passing into the large intestine unbound, potentially providing a competitive advantage to iron-dependent opportunistic pathogens in the large intestine.

In a large randomized control trial in children, iron supplementation was shown to promote the growth of pathogenic species (E. coli, S. aureus, and L. monocytogenes) and inhibited the growth of commensal species (Lactobacillus and Bifidobacterium). These pathogens are associated with enteric infections, while the commensals act on the host's immune system to prevent colonization and invasion by pathogens.

It is NOT known if iron supplementation during pregnancy impacts the maternal and infant microbiome and, by extension, how this affects the neonatal risk of infection and immune dysregulation. Vertical transmission of the maternal microbiome to the newborn is a major determinant of infant health. If maternal iron supplementation affects the infant's health, strategies would be required to mitigate this risk.

The investigators require preliminary data to show how oral iron supplementation alters the intestinal microbiome in women. The Investigators will recruit non-pregnant female participants as there is no risk of vertical transmission to an infant in non-pregnant women. The investigators will conduct the study in Australia because there is not a natural abundance of pathogens that could potentially cause harm to the women. Nevertheless, the investigators would expect a shift in the microbiome from non-iron to iron, requiring bacterial species to return to baseline after women stop taking the iron.

HYPOTHESIS: Daily iron supplementation versus placebo for 21 days will alter the stool microbiome composition compared to placebo in non-pregnant female participants of reproductive age.

METHODS: 80 female participants (18-45 y) will be randomized to receive capsules containing iron (65.7 mg of elemental iron as ferrous fumarate) or placebo to take daily for 21 days. Stool samples will be collected at baseline, 21 days, and 42 days (washout).

Study Timeline

• Study First Submitted: 2021-08-13
• Study First Submitted QC: 2021-08-27
• Study Start: 2021-08-31
• Study First Posted: 2021-09-02
• Status Verified: 2021-11
• Primary Completion: 2021-11-06
• Study Completion: 2022-01-01
• Last Update Submitted: 2023-04-11
• Last Update Posted: 2023-04-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 82

Inclusion Criteria

• Able to give informed consent

Exclusion Criteria

• Pregnant or breastfeeding.
• Planning on becoming pregnant
• Diagnosed with iron deficiency and/or anaemia in the previous three months
• Taken antibiotics in the past three months
• Taken iron containing supplements in the past three months

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Iron Supplement	Ferrous Fumarate	65.7 mg of iron as ferrous fumarate
Placebo	Placebo	0 mg of iron

Primary Outcome Measures

Name	Time	Method
Weighted UniFrac dissimilarity score	21 days	Measure of microbiota beta-diversity

Secondary Outcome Measures

Name	Time	Method
Taxonomic richness	21 days	Microbiota alpha-diversity score with adjustment for baseline levels
Shannon Wiener Diversity	21 days	Microbiota alpha-diversity score with adjustment for baseline levels
Faith's phylogenetic diversity	21 days	Microbiota alpha-diversity score with adjustment for baseline levels
Relative abundance of core bacterial taxa	21 days	Relative abundance of taxa present in \>40% of baseline samples, with adjustment for baseline levels
Bray-Curtis dissimilarity score	21 days	Measure of microbiota beta-diversity

Trial Locations

Locations (1)

SAHMRI; 🇦🇺 Adelaide, South Australia, Australia