Do Iron Supplements Impact the Gut Microbiome of Women of Reproductive Age?
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|ClinicalTrials.gov Identifier: NCT05033483|
Recruitment Status : Active, not recruiting
First Posted : September 2, 2021
Last Update Posted : November 30, 2021
|Condition or disease||Intervention/treatment||Phase|
|Iron-deficiency Microbial Colonization Anemia||Dietary Supplement: Ferrous Fumarate Dietary Supplement: Placebo||Not Applicable|
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 (Clinical Trial)|
|Actual Enrollment :||82 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||A randomized, controlled, researcher and participant blinded trial with two parallel groups|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
Supplements were packaged by LifeCare Compounding Pharmacy and labelled by staff not involved in the trial, with 2 colours per treatment group.
The randomisation schedule was prepared by an independent statistician. The schedule allocates women to one of the four colours in the ratio 1:1:1:1 using randomly permuted blocks.
|Official Title:||Do Iron Supplements Impact the Gut Microbiome of Women of Reproductive Age?|
|Actual Study Start Date :||August 31, 2021|
|Actual Primary Completion Date :||November 6, 2021|
|Estimated Study Completion Date :||December 1, 2021|
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
Active Comparator: Placebo
0 mg of iron
Dietary Supplement: Placebo
Gelatin capsule containing microcrystalline cellulose
Other Name: Control
- Weighted UniFrac dissimilarity score [ Time Frame: 21 days ]Measure of microbiota beta-diversity
- Bray-Curtis dissimilarity score [ Time Frame: 21 days ]Measure of microbiota beta-diversity
- Shannon Wiener Diversity [ Time Frame: 21 days ]Microbiota alpha-diversity score with adjustment for baseline levels
- Faith's phylogenetic diversity [ Time Frame: 21 days ]Microbiota alpha-diversity score with adjustment for baseline levels
- Taxonomic richness [ Time Frame: 21 days ]Microbiota alpha-diversity score with adjustment for baseline levels
- Relative abundance of core bacterial taxa [ Time Frame: 21 days ]Relative abundance of taxa present in >40% of baseline samples, with adjustment for baseline levels
- Weighted UniFrac dissimilarity score [ Time Frame: 42 days (washout) ]Measure of microbiota beta-diversity
- Shannon-Wiener diversity [ Time Frame: 42 days (washout) ]Microbiota alpha-diversity score with adjustment for baseline levels
- Bray-Curtis dissimilarity score [ Time Frame: 42 days (washout) ]Measure of microbiota beta-diversity
- Faith's phylogenetic diversity [ Time Frame: 42 days (washout) ]Microbiota alpha-diversity score with adjustment for baseline levels
- Taxonomic richness [ Time Frame: 42 days (washout) ]Microbiota alpha-diversity score with adjustment for baseline levels
- Relative abundance of core bacterial taxa [ Time Frame: 42 days (washout) ]Relative abundance of taxa present in >40% of baseline samples, with adjustment for baseline levels
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05033483
|Australia, South Australia|
|Adelaide, South Australia, Australia, 5000|
|Principal Investigator:||Steven Taylor, PhD||South Australian Health and Medical Research Institute|