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

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.

Study Overview

• Status: Completed
• Conditions: Iron-deficiency; Anemia; Microbial Colonization
• Intervention / Treatment: Dietary supplement: Ferrous Fumarate; Dietary supplement: Placebo

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 Type: Interventional
• Enrollment (Actual): 82
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • SAHMRI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Iron Supplement; 65.7 mg of iron as ferrous fumarate	Dietary supplement: Ferrous Fumarate; Gelatin capsule containing 200 mg ferrous fumarate and microcrystalline cellulose; Other Names: Iron Fumarate; ferro-tab
Active Comparator: Placebo; 0 mg of iron	Dietary supplement: Placebo; Gelatin capsule containing microcrystalline cellulose; Other Names: Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weighted UniFrac dissimilarity score	Measure of microbiota beta-diversity	21 days

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weighted UniFrac dissimilarity score	Measure of microbiota beta-diversity	42 days (washout)
Shannon-Wiener diversity	Microbiota alpha-diversity score with adjustment for baseline levels	42 days (washout)
Bray-Curtis dissimilarity score	Measure of microbiota beta-diversity	42 days (washout)
Faith's phylogenetic diversity	Microbiota alpha-diversity score with adjustment for baseline levels	42 days (washout)
Taxonomic richness	Microbiota alpha-diversity score with adjustment for baseline levels	42 days (washout)
Relative abundance of core bacterial taxa	Relative abundance of taxa present in >40% of baseline samples, with adjustment for baseline levels	42 days (washout)

Collaborators and Investigators

• Sponsor: South Australian Health and Medical Research Institute
• Collaborators: Flinders University
• Investigators: Principal Investigator: Steven Taylor, PhD, South Australian Health and Medical Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2021
• Primary Completion (Actual): November 6, 2021
• Study Completion (Actual): January 1, 2022

Study Registration Dates

• First Submitted: August 13, 2021
• First Submitted That Met QC Criteria: August 27, 2021
• First Posted (Actual): September 2, 2021

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: microbiome; women; iron supplements
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Physiological Effects of Drugs; Trace Elements; Micronutrients; Ferrous fumarate
• Other Study ID Numbers: Iron Mic

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Outlined below
• IPD Sharing Time Frame: Following final data analysis and primary publication
• IPD Sharing Access Criteria: Access to study data may be granted, upon review and approval of the Institutional Review Board, investigators, in accordance with South Australian Health and Medical Research Institute Women and Kids 'Guidelines and Agreement for the use of materials in an ancillary study associated with original clinical trials or cohort studies.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No