Iron Absorption From a Wheat-based Instant Cereal:Gut and Stable Isotope Studies in Kenyan Infants
Condition: Iron Absorption; Gut Microbiota
Study type: Interventional

Summary: 
      The aim of this study is to measure the effect of a prebiotic (high dose/low dose) mixture at
      different doses within a wheat-based instant cereal, on fractional iron absorption (FIA), gut
      microbiota and inflammation after three weeks. FIA will be compared with and without three
      weeks of pre-feeding with two different doses of the prebiotic mixture.
    

Detailed description: 
      Iron deficiency anemia (IDA) is prevalent in infants and preschool children in sub-Saharan
      Africa. Several studies have been conducted to mitigate IDA. Some of these studies had
      adverse effects on the gut microbiome and diarrhea due to the high iron dose administered in
      areas of high burden of malaria and other common childhood infections. As a potentially safer
      solution, we investigated the effect of lowering the iron dose in the iron supplements and
      including 7.5 g galacto-oligosaccharides (GOS). Findings from these studies demonstrated that
      in infants, consumption of iron and GOS improved iron status, improved the gut microbiota and
      reduced risk of illness. We recently demonstrated that habitual consumption of GOS for three
      weeks resulted in improved iron absorption that correlated with a decrease in colonic pH. It
      is not known whether other prebiotics or a combination will also result in increased iron
      absorption and what the effect of using half the dose of prebiotics would be. The composition
      of Human Milk Oligosaccharides (HMOs) in breast milk might be an important determinant of the
      gut microbiome composition and health of the breastfed infant by determining the composition
      of Bifidobacteria species that are the main commensal 'barrier' bacteria in the infant's gut
      microbiome. However, little is known about the specific HMOs composition of breast milk in
      African populations and the potential impact on the gut microbiota composition of the
      breastfed infants. We therefore aim to measure the effect of a prebiotic (high dose/low dose)
      mixture at different doses within a wheat-based instant cereal, on fractional iron absorption
      (FIA) from a wheat-based instant cereal containing no prebiotic. We will compare the FIA with
      and without three weeks of pre-feeding with two different doses of prebiotic mixture. In
      addition, we will investigate the effect of two different doses of this prebiotic (high
      dose/low dose) mixture on gut microbiota and inflammation after three weeks.

      In south coast Kenya, we will enroll 195 infants and randomize them into three intervention
      groups. Daily for 3 weeks, infants will consume a newly formulated wheat-based instant cereal
      (3.6 mg iron with Ascorbic acid (AA)) at home. Group 1 will receive the cereal with 7.5 g
      prebiotic mixture; group 2 will receive the cereal with 3 g prebiotic mixture and group 3
      will receive the cereal with no prebiotics. In a subset of 70 infants, we will administer
      four labelled test meals. Two test meals will be fed 2 weeks before beginning the
      intervention study to investigate the acute effect of prebiotics on FIA and the other two
      will be fed at the end of the 3 weeks intervention study to investigate the effect of chronic
      consumption of prebiotics on FIA. Breast milk samples from the mothers will be collected and
      analyzed for the composition of human milk oligosaccharides (HMOs). We hypothesize that: 1)
      Infants receiving the new wheat-based instant cereal containing prebiotic (high dose/low
      dose) mixture will have a higher iron absorption, and 2) higher fecal Bifidobacteria
      abundance than infants receiving the cereal without prebiotics; 3) in infants receiving the
      wheat-based instant cereal, the addition of 7.5 g of prebiotic (high dose/low dose) mixture
      will result in higher FIA, and 4) in greater ratio of Bifidobacteria to Enterobacteriaceae,
      lowest fecal calprotectin, intestinal fatty acid-binding protein (I-FABP) and lowest
      abundances of enteropathogens than the addition of 3 g of prebiotics; 5) the addition of 7.5
      g of prebiotic (high dose/low dose) mixture will result in greater FIA when administered
      acutely or chronically and these two effects will be additive; 6) the wheat-based instant
      cereal will improve iron status, including hemoglobin (Hb), plasma ferritin (PF) and soluble
      transferrin receptor (sTfR), and inflammation status, including C-reactive protein (CRP),
      alpha-1-acid glycoprotein (AGP), fecal calprotectin and I-FABP; 7) the wheat-based instant
      cereal will decrease fecal pH, thereby providing a less favorable growth environment for
      enteric pathogens; 8) Maternal secretor status will affect the infant gut microbiota, with
      infants of secretor mothers having higher abundances of Bifidobacterium and Bacteroides but
      lower abundances of enteropathogens; and 9) Effects of co-provision of prebiotic mixture on
      the infant gut microbiota and on iron absorption, will be stronger among infants of
      non-secretor mothers.

      This study will generate crucial data for optimizing iron and prebiotic-composition of
      wheat-based instant cereal designed for complementary feeding during infancy. This cereal
      could potentially be part of continued research on interventions to reduce the burden of IDA
      using safer formulations not adversely affecting the infant's gut microbiome.
    

Intervention name(s): FeFum and 7.5 g prebiotic mixture; FeFum and 3 g prebiotic mixture; Fefum and no prebiotic mixture
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): The 3 weeks intervention will consist of 24 g of wheat-based instant cereal and 90 ml of water per portion and will contain 3.6 mg FeFum and AA (molar ratio Fe:AA between 2.5 and 3) plus 7.5 g prebiotics mixture
The absorption study test meals will consist of 24 g wheat-based instant cereal and 90 ml of water per portion and additionally:
Test meal 1 will be composed of: 3.6 mg of Fe as 57FeFum and 0 g prebiotic mixture added extrinsically.
Test meal 2 will be composed of: 3.6 mg of Fe as 1.5 mg iron as 58FeFum, 2.09 mg iron as 56FeFum and 7.5 g prebiotic mixture added extrinsically.; Standard wheat-based instant cereal containing 3.6 mg FeFum and AA (molar ratio Fe:AA between 2.5 and 3) plus 3 g prebiotics mixture per portion; Standard wheat-based instant cereal containing 3.6 mg FeFum and AA (molar ratio Fe:AA between 2.5 and 3) per portion.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment