Effect of Iron Source on the Growth of Enteric Pathogens

Study Overview
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Brief Summary
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The World Health Organization recommends daily iron supplementation for infants and children (6 months-12 years). Based on the low cost and high bioavailability and efficacy, ferrous sulfate is typically the first choice for supplementation and fortification. The recommended dose of iron is set high to deliver adequate absorbed iron due to low rates of dietary iron absorption, which is typically <10%. Thus, the majority of dietary iron is not absorbed and travels to the colon. Unabsorbed iron in the colon may select for enteric pathogens at the expense of beneficial commensal bacteria and increase infection risk, including the clinical incidence of diarrhea. The objective of this study is to compare the effects of iron as ferrous sulfate (FeSO4) or FeSO4-enriched Aspergillus oryzae (Ao iron) on the growth and virulence of common enteric pathogens using an in vitro fecal fermentation model. Stool samples will be collected from children following ingestion of an iron supplement as either FeSO4 or Ao iron. Stool samples will be spiked with common enteric pathogens and outcome measures will be determined following in vitro fecal fermentation.

Official Title
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Effect of Iron-enriched Aspergillus Oryzae Compared to Ferrous Sulfate on the Growth and Virulence of Common Enteric Pathogens

Conditions
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Iron-deficiency, Iron Deficiency Anemia, Iron Deficiency Anemia Treatment

Intervention / Treatment
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* Dietary Supplement: FeSO4
* Dietary Supplement: Ao iron


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy children 5-12 y Willing to donate stool sample Exclusion Criteria: Currently taking antibiotics Currently taking a vitamin and mineral supplement containing iron Wards of the state, including children in foster care

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ferrous sulfate (FeSO4)<br>FeSO4 supplements containing 54 mg elemental iron | Dietary Supplement: FeSO4<br>* 2 FeSO4 supplements containing 27 mg elemental iron/supplements (54 mg total iron)<br>|
| Experimental: Ferrous sulfate-enriched Aspergillus oryzae (Ao iron)<br>Ao iron supplements containing 54 mg elemental iron | Dietary Supplement: Ao iron<br>* 2 Ao iron supplements containing 27 mg elemental iron/supplements (54 mg total iron)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of iron taken up by enteric pathogens | Iron uptake of common enteric pathogens will be determined in stool following in vitro fecal fermentation. | 0-24 hours | 
| Growth of enteric pathogens measured by optical density | Growth of common enteric pathogens will be determined in stool following in vitro fecal fermentation. | 0-24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut microbiome composition and diversity | Gut microbiome composition will be determined in stool following in vitro fecal fermentation using 16S rRNA gene sequencing. | 0-24 hours | 
| Individual fecal short chain fatty acid (SCFA) concentration | Individual SCFAs will be determined in stool following in vitro fecal fermentation by liquid chromatography-mass spectrometry. | 0-24 hours |