Heme and Non-heme Iron Intakes, Gut Microbiota, and Influence on Host Iron Absorption

Study Overview
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Brief Summary
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The FeMicrobiome study will evaluate gut microbiome features and their relationships with dietary iron absorption in healthy adults. We hypothesize that (1) the gut microbiota can be shaped by the heme and non-heme Fe content of the diet and that (2) this will influence individual variation in dietary Fe absorption.

Detailed Description
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Iron (Fe) is an essential micronutrient ingested as either heme Fe (from animal products) or non-heme Fe (from both plant and animal sources). Humans have no regulatable means of eliminating absorbed Fe, necessitating tight control of dietary Fe absorption. Likewise, native microbes have evolved efficient Fe sensing and utilization pathways to scavenge Fe from the gastrointestinal environment, resulting in a competition for Fe between the host and their microbiota. As growing numbers of Americans adopt plant-based diets, heme Fe intakes are markedly reduced. This may shift the gut microbiome as some gut microbiota cannot independently synthesize heme and require host dietary heme sources to support their heme-dependent functions. Animal data have recently discovered that other gut microbiota respond to a low non-heme Fe diet by producing metabolites that affect the absorption of non-heme Fe. To date, significant knowledge gaps exist on the interplay between dietary Fe sources, native gut microbes, and Fe utilization in humans. In the FeMicrobiome study, study investigators will recruit 120 adults who habitually ingest plant-based diets or habitually ingest diets containing animal protein (e.g., beef, pork, chicken, fish, and seafood). Fe absorption will be measured by using an in vivo, functional approach based on stable Fe isotopes (i.e., 57Fe). Study participants will consume 57Fe (as ferrous sulfate) in the fasted state followed by two standardized meals. Two weeks after Fe dosing, a blood sample will be collected from each participant and the amount of 57Fe incorporated into red blood cells will be measured using magnetic sector thermal ionization mass spectrometry. A stool sample will be collected near the time of 57Fe consumption. DNA will be extracted from this stool sample and sequenced using a high-depth shotgun metagenomic approach.

Official Title
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Heme and Non-heme Iron Intakes, Gut Microbiota, and Influence on Host Iron Absorption

Conditions
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Anemia, Iron Deficiency, Iron Overload

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults Age between 18- 40y Non-smoking Not currently taking vitamin, mineral, prebiotic, and probiotic supplements. Females: premenopausal and not pregnant or lactating No preexisting medical complications (such as eating disorders, hemoglobinopathies, malabsorption diseases, steroid use, substance abuse history, or taking medications known to influence iron homeostasis) Body mass index (BMI) between 18 - 27 kg/m2. Exclusion Criteria: BMI <18 or > 27 kg/m2, Age <18 y or > 40y, Not of Northern European or East Asian ancestry Smoking Pregnancy, lactating Have gastrointestinal disorders/malabsorption diseases/hemoglobinopathies/dietary restrictions/steroid use/ medication use of medications known to impact iron status, iron utilization or inflammatory status Currently take vitamin, mineral, prebiotic, and probiotic supplements. Recently received antibiotic treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percent of non-heme iron absorption | Percent non-heme iron absorption will be determined by red blood cell iron incorporation of stable 57Fe | 2-week | 
| The concentrations of hemoglobin | The concentrations of hemoglobin (d/dL) | baseline | 
| The concentrations of ferritin | The concentrations of ferritin (ug/L) | baseline | 
| Serum transferrin receptor | Serum transferrin receptor in mg/L | baseline | 
| The hematocrit | Blood hematocrit in % | baseline | 
| Habitual dietary information | Habitual dietary information will be obtained from Diet History Questionnaire III. | baseline | 
| Dietary information on the day prior to iron dosing | Detailed dietary information about all foods and beverages consumed on the day prior to iron dosing will be obtained from the Automated Self-Administered 24-Hour Dietary Assessment Tool. Total iron intake will be presented as a proportion of the daily iron requirement. Total heme and non-heme iron intakes will be quantified. | baseline | 
| Gut microbiome composition | Shotgun metagenomic sequencing will be performed to assess the gut microbiome compositions and gene functional features in a stool sample collected within one day before or after iron dosing. | baseline |